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The failure of antiviral vaccines is often associated with rapid viral escape from specific immune responses. In the past, conserved epitope or algorithmic epitope selections, such as mosaic vaccines, have been designed to diversify immunity and to circumvent potential viral escape. An alternative approach is to identify conserved stable non–HIV-1 self-epitopes present exclusively in HIV-1–infected cells. We showed previously that human endogenous retroviral (HERV) mRNA transcripts and protein are found in cells of HIV-1–infected patients and that HERV-K (HML-2)–specific T cells can eliminate HIV-1–infected cells in vitro. In this article, we demonstrate that a human anti–HERV-K (HML-2) transmembrane protein Ab binds specifically to HIV-1–infected cells and eliminates them through an Ab-dependent cellular cytotoxicity mechanism in vitro. Thus, Abs directed against epitopes other than HIV-1 proteins may have a role in eliminating HIV-1–infected cells and could be targeted in novel vaccine approaches or immunotherapeutic modalities.
NK cells play an integral role in the innate immune response by targeting virally infected and transformed cells with direct killing and providing help to adaptive responses through cytokine secretion. Whereas recent studies have focused on NK cells in HIV-1-infected adults, the role of NK cells in perinatally HIV-1-infected children is less studied. Using multiparametric flow cytometric analysis, we assessed the number, phenotype, and function of NK cell subsets in the peripheral blood of perinatally HIV-1-infected children on highly active antiretroviral therapy and compared them to perinatally exposed but uninfected children. We observed an increased frequency of NK cells expressing inhibitory killer Ig-like receptors in infected children. This difference existed despite comparable levels of total NK cells and NK cell subpopulations between the two groups. Additionally, NK cell subsets from infected children expressed, with and without stimulation, significantly lower levels of the degranulation marker CD107, which correlates with NK cell cytotoxicity. Lastly, increased expression of KIR2DL3, NKG2C, and NKp46 on NK cells correlated with decreased CD4+ T-lymphocyte percentage, an indicator of disease severity in HIV-1-infected children. Taken together, these results show that HIV-1-infected children retain a large population of cytotoxically dysfunctional NK cells relative to perinatally exposed uninfected children. This reduced function appears concurrently with distinct NK cell surface receptor expression and is associated with a loss of CD4+ T cells. This finding suggests that NK cells may have an important role in HIV-1 disease pathogenesis in HIV-1-infected children.
APOBEC3 proteins mediate potent antiretroviral activity by hypermutating the retroviral genome during reverse transcription. To counteract APOBEC3 and gain a replicative advantage, lentiviruses such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have evolved the Vif protein, which targets APOBEC3 proteins for proteasomal degradation. However, the proteasome plays a critical role in the generation of T cell peptide epitopes. Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and presentation of APOBEC3-derived T cell epitopes on the surfaces of lentivirus-infected cells remains unknown. Here, using peptides derived from multiple Vif-sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in both HIV-1-infected patients and SIV-infected rhesus macaques. These results raise the possibility that these T cell responses may be part of the larger antiretroviral immune response.
Psoriasis is a multifactorial, chronic disease of skin affecting 2-3% of the world’s population. Genetic studies of psoriasis have identified a number of susceptibility genes that are involved in anti-viral immunity. Furthermore, physiological studies have also found an increase in anti-viral proteins in psoriatic skin. These findings suggest the presence of an anti-viral state in psoriatic skin. However, the triggers for this anti-viral cascade and its consequences for host immunity are not known. Endogenous retroviruses have previously been described in many autoimmune diseases including psoriasis.
In the present study we examined the humoral immune response against human endogenous retrovirus-K (HERV-K) proteins and the cutaneous expression levels of multiple HERV-K genes in psoriasis patients and healthy controls.
In psoriatic sera we observed a significant decrease in IgM response against three HERV-K proteins: Env surface unit (SU), Env transmembrane protein (TM), and Gag capsid (CA) in comparison to sera obtained from blood bank healthy controls. A decrease in IgG response was also observed against CA. Furthermore, using quantitative RT-PCR we observed a decrease in the expression of HERV-K Env, Gag, Pol and Rec as well as ERV-9 genes in lesional psoriatic skin as compared to healthy skin.
Together, our results suggest that the pro-inflammatory, anti-viral state in psoriasis is associated with diminished expression of HERV-K gene transcripts and a concomitant decrease in humoral responses to HERV-K. Our results indicate that a simple model where continuous, minimally changing HERV-K expression serves as an antigenic trigger in psoriasis might not be correct and further studies are needed to decipher the possible relationship between psoriasis and HERVs.
Electronic supplementary material
The online version of this article (doi:10.1186/s12967-014-0256-4) contains supplementary material, which is available to authorized users.
Psoriasis; HERV-K; Immune response; Expression
The genetic diversity of HIV-1 represents a major challenge in vaccine development.
In this study, we establish a rationale for eliminating HIV-1–infected
cells by targeting cellular immune responses against stable human endogenous
retroviral (HERV) antigens. HERV DNA sequences in the human genome represent the
remnants of ancient infectious retroviruses. We show that the infection of
CD4+ T cells with HIV-1 resulted in transcription of the HML-2 lineage
of HERV type K [HERV-K(HML-2)] and the expression of Gag and Env proteins.
HERV-K(HML-2)–specific CD8+ T cells obtained from
HIV-1–infected human subjects responded to HIV-1–infected
cells in a Vif-dependent manner in vitro. Consistent with the proposed mode of
action, a HERV-K(HML-2)–specific CD8+ T cell clone exhibited
comprehensive elimination of cells infected with a panel of globally diverse HIV-1,
HIV-2, and SIV isolates in vitro. We identified a second T cell response that
exhibited cross-reactivity between homologous HIV-1-Pol and HERV-K(HML-2)-Pol
determinants, raising the possibility that homology between HIV-1 and HERVs plays a
role in shaping, and perhaps enhancing, the T cell response to HIV-1. This justifies
the consideration of HERV-K(HML-2)–specific and cross-reactive T cell
responses in the natural control of HIV-1 infection and for exploring
HERV-K(HML-2)–targeted HIV-1 vaccines and immunotherapeutics.
Invariant natural killer T (iNKT) cells are integral components of immune responses during many chronic diseases, yet their surface phenotypes, subset distribution, and polyfunctional capacity in this environment are largely unknown. Therefore, using flow cytometry, we determined iNKT phenotypic and functional characteristics in subjects with the chronic inflammatory disease sarcoidosis and matched controls. We found that sarcoidosis subjects displayed lower iNKT frequencies, which correlated with lung fibrosis, C-reactive protein levels, and other measures of clinical disease. The CD4− CD8− (DN) iNKT cell population was selectively lower in diseased individuals and the remaining DN iNKT cells exhibited higher frequencies of the activation markers CD69 and CD56. Functionally, both total IFN-gamma+ and the dual-functional IFN-gamma+ TNF-alpha+ iNKT cells were decreased in sarcoidosis subjects and these functional defects correlated with total iNKT circulating frequencies. As the loss of polyfunctionality can reflect functional exhaustion, we measured the surface antigens PD-1 and CD57 and found that levels inversely correlated with dual-functional iNKT cell percentages. These findings reveal that, similar to traditional T cells, iNKT cells may also undergo functional exhaustion, and that circulating iNKT frequencies reflect these defects. PD-1 antagonists may therefore be attractive therapeutic candidates for sarcoidosis and other iNKT-mediated chronic diseases.
invariant natural killer T cells; sarcoidosis; flow cytometry; inflammation; interferon-gamma
Natural killer (NK) cells are believed to play a role in human immunodeficiency virus type 1 (HIV-1) disease progression, and NK cell levels are reduced in individuals with chronic HIV-1 infection. Interleukin (IL)–2 therapy results in an expansion of CD4+ T cells as well as NK cells; however, little is known about the detailed effects of IL-2 therapy on NK cells in HIV-1 infection in general and in early infection in particular. Here, we investigated the effects of combined IL-2 therapy and antiretroviral therapy (ART) on the number, frequency, phenotype, and interferon (IFN)–γ production of NK cells in individuals with early HIV-1 infection. Patients randomized to receive combined ART and IL-2 therapy predominantly expanded CD56dim NK cells, and the expansion was greater than in patients randomized to receive ART alone. Importantly, NK cell receptor expression and IFN-γ production were maintained over time. This reconstitution of NK cells may be useful in helping contain viremia if patients discontinue therapy or develop drug resistance.
Type 1 long-interspersed nuclear elements (L1s) are autonomous retrotransposable elements that retain the potential for activity in the human genome but are suppressed by host factors. Retrotransposition of L1s into chromosomal DNA can lead to genomic instability, whereas reverse transcription of L1 in the cytosol has the potential to activate innate immune sensors. We hypothesized that HIV-1 infection would compromise cellular control of L1 elements, resulting in the induction of retrotransposition events. Here, we show that HIV-1 infection enhances L1 retrotransposition in Jurkat cells in a Vif- and Vpr-dependent manner. In primary CD4+ cells, HIV-1 infection results in the accumulation of L1 DNA, at least the majority of which is extrachromosomal. These data expose an unrecognized interaction between HIV-1 and endogenous retrotransposable elements, which may have implications for the innate immune response to HIV-1 infection, as well as for HIV-1-induced genomic instability and cytopathicity.
Expression of cell-intrinsic antiviral factors suppresses HIV-1 replication. We hypothesized that cellular activation modulates host restriction and susceptibility to HIV-1 infection. We measured the gene expression of 34 antiviral factors in healthy peripheral blood mononuclear cells (PBMC). Cellular activation induced expression of interferon-stimulated gene 15 (ISG15), tripartite motif 5α (TRIM5α), bone marrow stromal cell antigen 2 (BST-2)/tetherin, and certain apolipoprotein B mRNA editing enzyme 3 (APOBEC3) family members. Expression of RTF1, RNA polymerase II-associated factor 1 (PAF1), TRIM11, TRIM26, and BST-2/tetherin correlated with decreased HIV-1 infectivity. This report demonstrates synchronous effects of activation-induced antiviral genes on HIV-1 infectivity, providing candidates for pharmacological manipulation.
Human endogenous retrovirus (HERV)-specific T cell responses in HIV-1-infected adults have been reported. Whether HERV-specific immunity exists in vertically HIV-1-infected children is unknown. We performed a cross-sectional analysis of HERV-specific T cell responses in 42 vertically HIV-1-infected children. HERV (-H, -K, and -L family)-specific T cell responses were identified in 26 of 42 subjects, with the greatest magnitude observed for the responses to HERV-L. These HERV-specific T cell responses were inversely correlated with the HIV-1 plasma viral load and positively correlated with CD4+ T cell counts. These data indicate that HERV-specific T cells may participate in controlling HIV-1 replication and that certain highly conserved HERV-derived proteins may serve as promising therapeutic vaccine targets in HIV-1-infected children.
Chronic stress has deleterious effects on immune function, which can lead to adverse health outcomes. However, studies investigating the impact of stress reduction interventions on immunity in clinical research have yielded divergent results, potentially stemming from differences in study design and genetic heterogeneity, among other clinical research challenges. To test the hypothesis that reducing glucocorticoid levels enhances certain immune functions, we administered influenza vaccine once (prime) or twice (boost) to mice housed in either standard control caging or environmental enrichment (EE) caging. We have shown that this approach reduces mouse corticosterone production. Compared with controls, EE mice had significantly lower levels of fecal corticosterone metabolites (FCMs) and increased splenic B and T lymphocyte numbers. Corticosterone levels were negatively associated with the numbers of CD19+ (r2 = 0.43, p = 0.0017), CD4+ (r2 = 0.28, p = 0.0154) and CD8+ cells (r2 = 0.20, p = 0.0503). Vaccinated mice showed nonsignificant differences in immunoglobulin G (IgG) titer between caging groups, although EE mice tended to exhibit larger increases in titer from prime to boost than controls; the interaction between the caging group (control versus EE) and vaccine group (prime versus boost) showed a strong statistical trend (cage-group*vaccine-group, F = 4.27, p = 0.0555), suggesting that there may be distinct effects of EE caging on primary versus secondary IgG vaccine responses. Vaccine-stimulated splenocytes from boosted EE mice had a significantly greater frequency of interleukin 5 (IL-5)-secreting cells than boosted controls (mean difference 7.7, IL-5 spot-forming units/106 splenocytes, 95% confidence interval 0.24–135.1, p = 0.0493) and showed a greater increase in the frequency of IL-5–secreting cells from prime to boost. Our results suggest that corticosterone reduction via EE caging was associated with enhanced secondary vaccine responses, but had little effect on primary responses in mice. These findings help identify differences in primary and secondary vaccine responses in relationship to stress mediators that may be relevant in clinical studies.
The enormous sequence diversity of HIV remains a major roadblock to the development of a prophylactic vaccine and new approaches to induce protective immunity are needed. Endogenous retrotransposable elements (ERE) such as endogenous retrovirus K (ERV)-K and long interspersed nuclear element-1 (LINE-1) are activated during HIV-1-infection and could represent stable, surrogate targets to eliminate HIV-1-infected cells. Here, we explored the hypothesis that vaccination against ERE would protect macaques from acquisition and replication of simian immunodeficiency virus (SIV). Following vaccination with antigens derived from LINE-1 and ERV-K consensus sequences, animals mounted immune responses that failed to delay acquisition of SIVsmE660. We observed no differences in acute or set point viral loads between ERE-vaccinated and control animals suggesting that ERE-specific responses were not protective. Indeed, ERE-specific T cells failed to expand anamnestically in vivo following infection with SIVsmE660 and did not recognize SIV-infected targets in vitro, in agreement with no significant induction of targeted ERE mRNA by SIV in macaque CD4+ T cells. Instead, lower infection rates and viral loads correlated significantly to protective TRIM5α alleles. Cumulatively, these data demonstrate that vaccination against the selected ERE consensus sequences in macaques did not lead to immune-mediated recognition and killing of SIV-infected cells, as has been shown for HIV-infected human cells using patient-derived HERV-K-specific T cells. Thus, further research is required to identify the specific nonhuman primate EREs and retroviruses that recapitulate the activity of HIV-1 in human cells. These results also highlight the complexity in translating observations of the interplay between HIV-1 and human EREs to animal models.
We aimed to investigate whether the character of the immunodominant HIV-Gag peptide (variable or conserved) targeted by CD8+ T cells in early HIV infection would influence the quality and quantity of T cell responses, and whether this would affect the rate of disease progression. Treatment-naive HIV-infected study subjects within the OPTIONS cohort at the University of California, San Francisco, were monitored from an estimated 44 days postinfection for up to 6 years. CD8+ T cells responses targeting HLA-matched HIV-Gag-epitopes were identified and characterized by multicolor flow cytometry. The autologous HIV gag sequences were obtained. We demonstrate that patients targeting a conserved HIV-Gag-epitope in early infection maintained their epitope-specific CD8+ T cell response throughout the study period. Patients targeting a variable epitope showed decreased immune responses over time, although there was no limitation of the functional profile, and they were likely to target additional variable epitopes. Maintained immune responses to conserved epitopes were associated with no or limited sequence evolution within the targeted epitope. Patients with immune responses targeting conserved epitopes had a significantly lower median viral load over time compared to patients with responses targeting a variable epitope (0.63 log10 difference). Furthermore, the rate of CD4+ T cell decline was slower for subjects targeting a conserved epitope (0.85% per month) compared to subjects targeting a variable epitope (1.85% per month). Previous studies have shown that targeting of antigens based on specific HLA types is associated with a better disease course. In this study we show that categorizing epitopes based on their variability is associated with clinical outcome.
Objective: The majority of infants born, in developed countries, to HIV-1 positive women are exposed to the HIV-1 virus in utero or peri/post-partum, but are born uninfected. We, and others, have previously shown HIV-1 specific T cell responses in HIV-1 exposed seronegative (HESN) neonates/infants. Our objective in this study was to examine the rate of decay in their HIV-1 specific T cell response over time from birth. Design: Cross-sectional and longitudinal studies of HIV-1 specific T cell responses in HESN infants were performed. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 18 HIV-1 DNA PCR negative infants born to HIV-1 infected mothers receiving care at the Jacobi Medical Center, Bronx, NY, USA. PBMC were examined for T cell responses to HIV-1 antigens by interferon-gamma (IFN-γ) ELISPOT. Results: PBMC from 15 HESN neonates/infants were analyzed. We observed a decay of HIV-1 specific T cell responses from birth at a rate of −0.599 spot forming unit/106 cells per day, with a median half-life decay rate of 21.38 weeks (13.39–115.8). Conclusion: Our results support the dynamic nature of T cell immunity in the context of a developing immune system. The disparate rate of decay with studies of adults placed on antiretroviral drugs suggests that antigen specific T cell responses are driven by the natural rate of decay of the T cell sub-populations themselves.
HIV-1; exposed seronegative; vertically exposed; neonates; T cells
Human Endogenous Retroviruses (HERVs) comprise about 8% of the human genome and have lost their ability to replicate or to produce infectious particles after having accumulated mutations over time. We assessed the kinetics of expression of HERV-K (HML-2) Envelope mRNA transcript and surface unit (SU) and transmembrane (TM) subunit proteins during HIV-1 infection. We also mapped the specificity of the humoral response to HERV-K (HML-2) Envelope protein in HIV-1 infected subjects at different stages of disease, and correlated the response with plasma viral load.
We found that HIV-1 modified HERV-K (HML-2) Env mRNA expression, resulting in the expression of a fully N-glycosylated HERV-K (HML-2) envelope protein on the cell surface. Serological mapping of HERV-K (HML-2) envelope protein linear epitopes revealed two major immunogenic domains, one on SU and another on the ectodomain of TM. The titers of HERV-K (HML-2) TM antibodies were dramatically increased in HIV-1 infected subjects (p < 0.0001). HIV-1 infected adults who control HIV-1 in the absence of therapy (“elite” controllers) had a higher titer response against TM compared to antiretroviral-treated adults (p < 0.0001) and uninfected adults (p < 0.0001).
These data collectively suggest that HIV-1 infection induces fully glycosylated HERV-K (HML-2) envelope TM protein to which antibodies are induced. These anti-HERV-K (HML-2) TM antibodies are a potential marker of HIV-1 infection, and are at higher titer in elite controllers. HERV-K (HML-2) envelope TM protein may be a new therapeutic target in HIV-1 infection.
HIV; Antibody; HERV; Endogenous retroviruses; Transmembrane; Envelope; Elite controllers; Alternative transcripts
The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4∶CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/µl (“non-controllers”, n = 42), those with undetectable viral loads on ART (“ART-suppressed”, n = 53), and HIV-uninfected subjects (n = 22). In addition, T cell phenotype and function were examined in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects. CD4∶CD8 ratio in non-controllers, ART-suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P<0.0001 for all comparisons). The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with no change in the expanded CD8+ T cell population. Expansion of differentiated (CD28−CD27−CD45RA+/−CCR7−) T cell subpopulations persisted despite ART and minimal changes were noted in naïve T cell frequencies over time. Increased number of CD8+CD28− T cells and increased CD8+ CMV-specific T cell responses were associated with a decreased CD4∶CD8 ratio. Measures of T cell function demonstrated persistence of high frequencies of CD8+ T cells producing IFN–γ. Lastly, though all CD8+ subpopulations demonstrated significantly lower Ki67 expression in ART-suppressed subjects, CD4+ T cell subpopulations did not consistently show this decrease, thus demonstrating different proliferative responses in the setting of T cell depletion. In summary, this study demonstrated that CD4∶CD8 ratios remained significantly decreased and naïve T cell numbers were slow to increase despite long-term viral suppression on ART. In addition, there is a evidence of differential regulation of the CD4+ and CD8+ T cell subpopulations, suggesting independent homeostatic regulation of the two compartments.
A subset of CD3negCD56negCD16+ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.
Using CD7 as an additional NK cell marker, we found that CD3negCD56negCD16+ cells are a heterogeneous population comprised of CD7+ NK cells and CD7neg non-classical myeloid cells. CD7+CD56negCD16+ NK cells are significantly expanded in HIV-1 infection. CD7+CD56negCD16+ NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7+CD56+CD16+ NK cells. CD7+CD56neg NK cells in healthy donors produced minimal IFNγ following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7+CD56+ NK cells. HIV-1 infection resulted in reduced IFNγ secretion following K562 or cytokine stimulation by both NK cell subsets compared to healthy donors. Decreased granzyme B and perforin expression and increased expression of CD107a in the absence of stimulation, particularly in HIV-1-infected subjects, suggest that CD7+CD56negCD16+ NK cells may have recently engaged target cells. Furthermore, CD7+CD56negCD16+ NK cells have significantly increased expression of CD95, a marker of NK cell activation.
Taken together, CD7+CD56negCD16+ NK cells are activated, mature NK cells that may have recently engaged target cells.
Natural killer cells; NK cells; CD7; Human immunodeficiency virus; HIV-1; HIV pathogenesis; CD56neg NK cells
Several host-encoded antiviral factors suppress HIV-1 replication in a cell-autonomous fashion in vitro. The relevance of these defenses to the control of HIV-1 in vivo remains to be elucidated. We hypothesized that cellular restriction of HIV-1 replication plays a significant role in the observed suppression of HIV-1 in "elite controllers", individuals who maintain undetectable levels of viremia in the absence of antiretroviral therapy (ART). We comprehensively compared the expression levels of 34 host restriction factors and cellular activation levels in CD4+ T cells and sorted T cell subsets between elite controllers, HIV-1-infected (untreated) non-controllers, ART-suppressed, and uninfected individuals.
Expression of schlafen 11, a codon usage-based inhibitor of HIV-1 protein synthesis, was significantly elevated in CD4+ T cells from elite controllers as compared to both non-controllers (p = 0.048) and ART-suppressed individuals (p = 0.024), with this effect most apparent in central memory CD4+ T cells. Schlafen 11 expression levels were comparable between controllers and uninfected individuals. Cumulative restriction factor expression was positively correlated with CD4+ T cell activation (r2 = 0.597, p < 0.0001), viral load (r2 = 0.34, p = 0.015), and expression of ISG15 (r2 = 0.73, p < 0.0001), a marker of interferon exposure. APOBEC3C, APOBEC3D, CTR9, TRIM26, and TRIM32 were elevated in elite controllers with respect to ART-suppressed individuals, while levels were comparable to uninfected individuals and non-controllers.
Host restriction factor expression typically scales with cellular activation levels. However, the elevated mRNA and protein expression of schlafen 11, despite low activation and viral load, violates the global pattern and may be a signature characteristic of HIV-1 elite control.
Elite controllers; Intrinsic immunity; Retroviral restriction factors; APOBEC3; BST2/tetherin; TRIM; schlafen 11; p21; T cell activation
The human fetal immune system is naturally exposed to maternal allogeneic cells, maternal antibodies, and pathogens. As such, it is faced with a considerable challenge with respect to the balance between immune reactivity and tolerance. Here, we show that fetal natural killer (NK) cells differentiate early in utero and are highly responsive to cytokines and antibody-mediated stimulation but respond poorly to HLA class I–negative target cells. Strikingly, expression of killer-cell immunoglobulin-like receptors (KIRs) did not educate fetal NK cells but rendered them hyporesponsive to target cells lacking HLA class I. In addition, fetal NK cells were highly susceptible to TGF-β–mediated suppression, and blocking of TGF-β signaling enhanced fetal NK cell responses to target cells. Our data demonstrate that KIR-mediated hyporesponsiveness and TGF-β–mediated suppression are major factors determining human fetal NK cell hyporesponsiveness to HLA class I–negative target cells and provide a potential mechanism for fetal-maternal tolerance in utero. Finally, our results provide a basis for understanding the role of fetal NK cells in pregnancy complications in which NK cells could be involved, for example, during in utero infections and anti-RhD–induced fetal anemia.
The expression of endogenous retrotransposable elements including Long Interspersed Nuclear Element-1 (LINE-1 or L1) and Human Endogenous Retrovirus (HERV)-K accompanies neoplastic transformation and infection with viruses such as HIV. The ability to engender immunity safely against such self-antigens would facilitate the development of novel vaccines and immunotherapies. Here we address the safety and immunogenicity of vaccination with these elements. We employed immunohistochemical analysis and literature-precedent to identify potential off-target tissues in humans and establish their translatability in preclinical species to guide safety assessments. Immunization of mice with murine L1 Open Reading Frame-2 (L1O2) induced strong CD8 T cell responses without detectable tissue damage. Similarly, immunization of rhesus macaques with human L1O2 (96% identity with macaque), and Simian ERV (SERV)-K Gag and Env induced polyfunctional T cell responses to all antigens, and antibody responses to SERV-K Env. There were no adverse safety or pathology findings related to vaccination. These studies provide the first evidence that immune responses can be induced safely against this class of self antigens, and pave the way for their investigation as HIV- or tumor-associated targets.
Genetic variability is a major feature of the human immunodeficiency virus type 1 (HIV-1) and considered the key factor to frustrating efforts to halt the virus epidemic. In this study, we aimed to investigate the genetic variability of HIV-1 strains among children and adolescents born from 1992 to 2009 in the state of Sao Paulo, Brazil.
Plasma and peripheral blood mononuclear cells (PBMC) were collected from 51 HIV-1-positive children and adolescents on ART followed between September 1992 and July 2009. After extraction, the genetic materials were used in a polymerase chain reaction (PCR) to amplify the viral near full length genomes (NFLGs) from 5 overlapped fragments. NFLGs and partial amplicons were directly sequenced and data were phylogenetically inferred.
Of the 51 samples studied, the NFLGs and partial fragments of HIV-1 from 42 PBMCs and 25 plasma were successfully subtyped. Results based on proviral DNA revealed that 22 (52.4%) patients were infected with subtype B, 16 (38.1%) were infected with BF1 mosaic variants and 4 (9.5%) were infected with sub-subtype F1. All the BF1 recombinants were unique and distinct from any previously identified unique or circulating recombinant forms in South America. Evidence of dual infections was detected in 3 patients coinfected with the same or distinct HIV-1 subtypes. Ten of the 31 (32.2%) and 12 of the 21 (57.1%) subjects with recovered proviral and plasma, respectively, protease sequences were infected with major mutants resistant to protease inhibitors. The V3 sequences of 14 patients with available sequences from PBMC/or plasma were predicted to be R5-tropic virus except for two patients who harbored an X4 strain.
The high proportion of HIV-1 BF1 recombinant, coinfection rate and vertical transmission in Brazil merits urgent attention and effective measures to reduce the transmission of HIV among spouses and sex partners.
The immunopathogenic mechanisms leading to psoriasis remain unresolved. CD57 is a marker of replicative inability and immunosenescence on CD8+ T cells and the proportion of CD57 expressing CD8+ T cells is increased in a number of inflammatory conditions.
We examined the expression of CD57 on T cells in the skin of patients affected with psoriasis, comparing lesional and unaffected skin. We also assessed functionality of the T cells by evaluating the secretion of several inflammatory cytokines (IL-17A, IFN-gamma, IL-2, IL-33, TNF-alpha, IL-21, IL-22, and IL-27), from cell-sorted purified CD4+ and CD8+ T cells isolated from lesional and unaffected skin biopsies of psoriasis patients.
We observed that the frequency of CD57+CD4+ and CD57+CD8+ T cells was significantly higher in unaffected skin of psoriasis patients compared to lesional skin. Sorted CD4+ T cells from psoriatic lesional skin produced higher levels of IL-17A, IL-22, and IFN-gamma compared to unaffected skin, while sorted CD8+ T cells from lesional skin produced higher levels of IL-17, IL-22, IFN-gamma, TNF-alpha, and IL-2 compared to unaffected skin.
These findings suggest that T cells in unaffected skin from psoriasis patients exhibit a phenotype compatible with replicative inability. As they have a lower replicative capacity, CD57+ T cells are less frequent in lesional tissue due to the high cellular turnover.
HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4+ T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. The CD39 ectonucleotidase receptor is expressed on CD4+ T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39+CD25+) and effector (CD39+CD25−) function. Here, we investigated the expression of CD39 on CD4+ T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. The frequency of CD39+ CD4+ T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39+CD25− CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39+CD25+ regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39−CD25+ T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4+ T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4+ T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of HAM/TSP.
Human T-lymphotropic virus type 1 (HTLV-1) has been estimated to infect 10–20 million worldwide. The majority of infected individuals are asymptomatic, however, 2% to 3% develop a neurodegenerative disorder called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The reasons why persons with HTLV-1 develop these complications appear to be multiple and complex. Cellular immune response has been implicated in the development of inflammatory alterations in these patients, however the pathogenic mechanisms for disease progression remain unclear. Regulatory CD4+ T cells (Treg) and Th17 cells derive from a common progenitor and conflicting results regarding frequency and function are found in the development of HAM/TSP. The expression of the CD39 ectoenzyme, a molecule that can mediate immunostimulatory and inhibitory effects, is useful to define IL-17 secreting cell populations, suppressive CD4+ T cells and CD4+ T cells with immunostimulatory properties. The interplay of these T-cell subsets may reveal important aspects of HAM/TSP pathogenesis. In this study, we performed an evaluation of the immunoregulatory CD4+ T-cell subsets defined by CD39 expression including Th17 cells. Our results present phenotypic and functional alterations in the CD4+ T cell profile that could account for the transition from asymptomatic status to HAM/TSP, predicting clinical disease risk and tracking disease progression.
An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial.
Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets.
Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.
HTLV-I; Human endogenous retrovirus; T-cells; HTLV-1-associated myelopathy/tropical spastic paraparesis
Previous genetic and functional studies have implicated the human endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1 locus in the MHC region as a candidate psoriasis gene. Here, we describe a variant discovery and case-control association study of HERV-K dUTPase variants in 708 psoriasis cases and 349 healthy controls. Five common HERV-K dUTPase variants were found to be highly associated with psoriasis, with the strongest association occurring at the missense SNP rs3134774 (K158R, p=3.28 × 10-15, OR=2.36 [1.91-2.92]). After adjusting the association of the HERV-K dUTPase variants for the potential confounding effects of HLA alleles associated with psoriasis, the HERV-K SNPs rs9264082 and rs3134774 remained significantly associated. Haplotype analysis revealed that HERV-K haplotypes containing the non-risk alleles for rs3134774 and rs9264082 significantly reduced the risk of psoriasis. Functional testing showed higher antibody responses against recombinant HERV-K dUTPase in psoriasis patients compared to controls (p<0.05), as well as higher T-cell responses against a single HERV-K dUTPase peptide (p<0.05). Our data support an independent role for the HERV-K dUTPase on psoriasis susceptibility, and suggest the need for additional studies to clarify the role of this dUTPase in the pathogenesis of psoriasis.


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I have a bit of an obsession:
Helping my clients to embody the authentic, unapologetic expression they were born with.
My other obsession?
Spreading Radical Voice Love -
AKA that fully embodied feeling that your voice is not only worthy of being heard it’s so so needed in the world (and using it is what truly makes you a Vocal Warrior).

domain: artistic


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I discover that at any time when I’m going on trip, as aware as I attempt to be with my meals decisions, I nonetheless can’t appear to have a traditional day and hold my blood sugars in vary. These rollercoaster days actually put a damper on my time away. Why do they occur? For fairly a number of causes, a few of which might have been prevented, and others which are mysterious.
You already know all the apparent causes for our blood sugar spiking, equivalent to a high-carb meal, skipping medicine, or not taking sufficient insulin. But there are so many factors that affect blood sugar, a few of which come into play on trip greater than you would possibly anticipate.
Here are some shocking causes for erratic blood sugars and what you are able to do about it.
Did you understand accommodations and eating places add pancake batter to their scrambled eggs?
I’ll always remember my first diabetes journey, Bolus & Barbells, the place a bunch of like-minded folks residing with kind 1 diabetes bought collectively for a weekend of studying, lifting, and plenty of laughs! It was surreal to see so many individuals sporting gadgets, taking pictures, and listening to Dexcom alarms that didn’t belong to me. One factor all of us observed: regardless of our efforts to eat a low-carb breakfast, our blood sugars stored on rising. After talking to the resort supervisor, we realized it’s commonplace so as to add pancake batter to scrambled eggs. Apparently, it helps with the construction, consistency, and style.
Opt for freshly cooked eggs if it’s an possibility, and relaxation assured they don’t seem to be including any secret carbohydrates.
If the bacon is additional candy, it’s doused in sugar!
Bacon is a scrumptious, low-carb, and high-protein meals that shouldn’t increase your blood sugars. However, when bacon is cured with salt it must be offset with some sugar, which additionally helps add some taste. Some eating places and accommodations use sugar extra liberally than others. If your bacon tastes additional candy and succulent, that is in all probability why! Not certain about your bacon? Make certain to ask.
Climate can have an effect on blood sugars, alter accordingly!
Extreme temperatures in both course can play a significant position in how your blood sugar behaves. Ben Tzeel, a registered dietician and founding father of (*5*), explains: “In cold weather, some people experience a drop in insulin sensitivity, so their numbers may run higher. Many also experience a greater number of lows when they’re active in the cold since their bodies have to work harder to keep them warm and provide fuel for activity.”
Hot climate can have the same unpredictable effect: blood sugar can spike, particularly in the event you’re dehydrated, however it could additionally plummet if the warmth will increase your pace of insulin absorption.
Whether you’re snowboarding within the French Alps or mendacity on a seashore in Tahiti, you ought to be conscious of the attainable fluctuations and alter your medicine and/or insulin accordingly.
Hydration is vital
It’s arduous sufficient to recollect to drink sufficient water once we are house and in our routines, not to mention once we are away and distracted. On trip, you might be strolling extra, sitting within the solar, and in addition take pleasure in a number of extra alcoholic drinks than regular, all of which might result in additional dehydration. When we’re dehydrated, the sugar in our blood turns into extra concentrated and might trigger excessive blood sugars. Dr. Mike Natter, MD, recommends “stay well hydrated and consider basal and insulin-to-carb ratio adjustments in conjunction with your doctor.”
Try and keep in mind to remain hydrated – it could aid you keep away from elevated numbers, and also you’ll really feel higher too!
Stick to your schedule
Vacation means a break from the routines you rely on to make healthful selections. For me, my final journey had me up at 4:00 am, which is three hours earlier than I normally take my long-lasting insulin. Oops! I fully forgot my morning dose, and it was one other 5 hours earlier than I spotted it. Had I set a reminder, I’d have prevented a gradual blood sugar climb, and the annoying troubleshooting I needed to do throughout the airplane trip. Also, be aware of time zone adjustments and attempt to take all medicine and insulin concurrently regular.
Vacation is meant to be a time to chill out and go away your worries behind. Unfortunately, we by no means get a break from managing our diabetes. But in the event you stay vigilant you may keep away from a number of the blood sugar spikes and drops, permitting you to be current and benefit from the second!
Read extra about Dexcom, insulin, Intensive administration, low-carb food plan, trip.

domain: medical


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Play Free Mobile Games on 2FlashGames.Com
Play most popular mobile games, anytime, anywhere on your mobile devices
The little aliens' flying saucer ran out of fuel and in an attempted emergency landing it came crashing down right into a barn here on earth. Now the aliens have to escape from the barn and find new fuel to continue on the their journey to the stars. Luckily they are able to alter their form which enables them to overcome all the obstacles in their way. In this fun and free brain teasing game it is you objective to smooth the way out of each level for the aliens by using their shape shifting abilities. With good timing and clever use of the environment you will succeed. Play now!
Language: deutsch, english, français, italiano, português, Русский язык, español, Türkçe
Rating: 4 out of 5
2020 Connect Deluxe
2020 Connect Deluxe , the most addictive logic puzzle game is back in a definitive edition that is even more fun! The player’s task is to place at least four blocks with the same number on it next to each other so they get merged. 2020 Connect Deluxe takes the best ideas of games like Merged and 2048 and turns it into a total blast. Merging more than four blocks will reward you with coins that later can be spend to purchase cool boosters. Take your time, plan ahead and think for a long as you need to, there is no hurry. Play 2020 Connect Deluxe now for free! How far can you make it? Will you be able to get the legendary 8192 blocks to merge?
Puzzle Games, Board Games
Try to create a chain reaction that pops all of the flowers But be careful, as you only have a few clicks available to clear the level, so dont waste any.
Puzzle Games, Skill
Valiant Knight - STP
The Valiant Knight is back in this brand new platform style adventure! Vicious orcs have abducted his beloved wife the princess and now they demand staggeringly high ransom. The chronically broke king once again sends our hero out on a dangerous journey to save his daughter and of course to collect some gold. On his way the Valiant Knight has to solve puzzles and face dangers beyond belief, so it is once again your turn to take good care of the Valiant Knight and save him from any harm. With a single tap or click you can change the direction, the brave knight is taking. If you click or press a bit longer, the knight starts a sprint that enables him to overcome obstacles, run from enemies and avoid traps. Play now for free!
Puzzle Games, Classic Games, Skill, Jump 'N' Run Games, Action Games

domain: entertainment


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Cote d’Azur and the Italian Riviera
From Monaco’s spectacular marina and designer boutiques to the Italian Riviera’s elite yachting capital of Portofino, the Cote d’Azur and Italian Riviera offer magnificent countryside, secluded beaches and a bustling nightlife.
Fire and Ice Sunseeker 90 Superyacht
Enjoy a romantic break onboard superyacht Fire and Ice. She is available for charter for £33,000 GBP, for four days and three nights.
From Antibes, cruise to the sophisticated principality of Monaco for the night. Enjoy dinner at L’Hermitage before heading to Monaco's famous casinos.
Cruise to the picture-perfect hideaway of Portofino and dine onboard your exclusive private charter yacht.
Cruise to the Cinque Terre, exploring the rugged coast of the Italian Riviera, and return to Portofino to enjoy dinner at the Splendido. Guests also have the option of soaking up Porofiono’s bustling nightlife at the ‘Covo’ nightclub.
Return to Antibes for departure.
RE1 Sunseeker Predator 92 Superyacht
Indulge in Michelin Star Dining onboard High Energy; the superyacht is available for charter for €44,000 EUR, for four days and three nights.
Embark at the picturesque town of Portofino after a night’s stay at Hotel Splendido. Cruise to Villefranche Sur Mer for the day and enjoy dinner at La Mere Germaine.
Cruise to the beautiful and secluded Porquerolle Island. Beyond its rocky shores the island offers long, sandy beaches and unspoiled natural beauty. After a day of utter relaxation, dinner is served under the stars onboard High Energy.
From Porquerolle Island, cruise to the bustling port of St Tropez; an elegant seaide town boasting private beaches, and prestigious clubs and restaurants. Enjoy dinner at Spoon, Hotel Byblos before heading on to the sister nightclub Caves du Roy.
Cruise to Portofino for departure.
For inspiration for your next charter holiday destination, browse the Superyachts.com Destination Guide.

domain: travel


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They are simple but the design is definitely one that cannot just be ignored. It has a slender and straight trunk and right on top is a thick glass lamp that resembles an empty glass of water. The Siblings looks ultra-modern and chic, but still neutral and simple enough to be a flexible piece of light decoration. Thus, you can place them in different locations, without worry that they might not fit in or stand out enough. The Siblings will definitely belong with ease and style.
This specie of The Siblings is the table lamp. The colors are available in Oak, RAL 9005, and RAL 9010. That means you have a selection colors you can choose from to suit your needs and personal preferences. They are also made for indoor use only.
The materials used for this exceptional piece are guaranteed to be of high quality and standard. It has a wooden base, borosilicate glass for the lamp, and LED for lighting. The finishes for the trunk are natural oiled, tainted black, or white oak depending on the color, while the lamp is a tough clear glass.
The Siblings is just one of the lamps belonging in the amazing and unique modern collection of PER/USE, a Belgian company that brings high quality lighting to our homes and buildings. The design was made out of Frederik Delbart’s passionate labor and creative thinking.


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Home › John Gleisner review of A Certain Grace › John Gleisner review of A Certain Grace
John Gleisner review of A Certain Grace
"A Certain Grace" by Tony Maturin, 2006
A review by John Gleisner
A Certain Grace, Anthony Maturin, 2006
Price NZ$70 (discount for Friends). All profits from sales are going to some small NGOs working to alleviate poverty on the rural fringes of society in Cambodia.
Available at some bookshops, or email the author, or write to 4 Hoggard Street, Vogeltown, Wellington 6021.
Readers of the Newsletter may recall Tony Maturin’s piece ‘Beethoven in Cambodia’, some reflections on preparing this book. Tony recently spent 2 years in Cambodia together with his wife Sandra who was working as Research Advisor to the Buddhist Institute. Both were supported by VSA New Zealand. Tony is a seasoned overseas volunteer having previously served in Vanuatu, Central America and Iraq. On this occasion he concentrated on photographing the most disadvantaged people in Cambodia. He was assisted by an interpreter and was able to visit a dozen or so NGO’s in and around Phnom Penh but also went to Battambang and Sihanoukville, towns further away.
The result is a remarkable collection of photographs, beautifully displayed with an accompanying commentary. Presented in sepia they reminded me of the iconic works of Sebastio Selgado. Almost all the photos are of people and Tony has the skill of capturing his subjects in beautifully relaxed and natural settings. As with Selgado’s pictures, though all these are from Cambodia, they are universal: they represent mankind’s poorest and most destitute. That the photographs are beautiful does not distract from their haunting appeal: "we too are people who share this earth with you". Photographs of street children, garbage collectors, prostitutes, victims of the genocide, AIDS sufferers and drug addicts.
Tony says in the introduction that his purpose was not just to show the terrible damage people are suffering but also to emphasize the amazing spirit of resilience, courage, dignity and even triumph he discovered. Yet even these attributes cannot take away the fact that in sum these people are the expression of a world full of injustice.
Tony is to be congratulated on this wonderful book. Treat yourself! You will not be disappointed. Or urge your librarian to buy a copy.
A comment by Rae Julian, Council for International Development
All those who have worked, lived or travelled in Cambodia cannot help but be entranced by this book. It is the record of two years of Tony Maturin’s life when he accompanied his wife, Sandra Jones on a VSA assignment in Phnom Penh. Rather than just provide household support, Tony embarked on his own journey to explore the culture of the Khmer, with assistance from a wide range of Cambodian individuals and NGOs. The result is a comprehensively sepia-illustrated book that discusses a range of themes chosen to tell the stories of the people and their spirit; how they came out of over 30 years of war or conflict to turn their tragedy into survival and, for many, triumph.
I found that reading this book took me back to my years in Cambodia. It is profoundly moving and reinforces my memories of the strength and endurance of the Khmer people.

domain: literature


This Windows laptop was rolled out in 2017 with college students as its target market. Surface Laptop offers a touch-screen display and an Alcantara-fabric-covered keyboard. It’s interesting to note that the screen is not detachable from the keyboard. Still, the touch screen, trackpad, and stylus pen provide a range of motions for the laptop.
For its CPU, Surface Laptop utilizes Intel®’s seventh-generation Kaby Lake Core i5 and i7 processors. The basic configuration features a Core m3 processor, a 4 GB RAM, and a 128 GB internal storage.
Surface Laptop initially ran on Windows 10 S, which was replaced with Windows 10 in S Mode or upgradeable to Windows 10 Pro. One can sign in through Windows Hello face-recognition camera.


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Daily Energy Shift: Rise up! Have you been focusing on lower energies? Feeling tired and run down? RISE UP! Get your mind focused on the light, on God, on love. Raise your energy, raise your thoughts, raise yourself up from the darkness, shadow self. Rise up!
Sign Up For A Free 15-Minute Energy Scan and Coaching Session And Receive The Video Course: 3 Steps To Shift Your Energy
“Gabrielle is an excellent coach. Her straight forward, patient, honest, approach made me feel comfortable on more than one occasion. This was especially beneficial when I was having difficulty deciding on a goal and feeling very bewildered about it. The questions that she asked me helped me to get clear on what I really wanted to do and what was really the best option for me at a time. She listened and understood that I needed to feel less overwhelmed and frustrated by competing priorities and life stressors so that I could move forward. As a result of receiving coaching from Gabrielle, I was able to put some activities in motion and make meaningful progress. She even gave me valuable feedback that helped with the building of my website and creating clarity in the messages I wanted to share.”

domain: psychology


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These are some pictures I took to showcase some outfits that I have put together since moving to Montreal. I really wanted to experiment with my surroundings and capture different parts of the city.
This outfit Picture was taken in front of one of the many beautiful brick walls in Montreal.
The next series of outfit pictures were taken in an alley way in Plateau Mont-Royal. This alley way was filled with so much character and some amazing graffiti.

domain: geography


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WOOD COUNTY, WV (WOWK) – A man has died after a head-on crash in Wood County involving a motorcycle.
According to the Wood County Sheriff’s Office, the two-vehicle crash happened around 5 p.m. Saturday, Oct. 21, at the intersection of Staunton Turnpike and Leechtown Lane. Deputies say the motorcycle was traveling west, allegedly at “an extremely high rate of speed,” when it went left of center, striking a car that was traveling east.
The Wood County Sheriff’s Office says the motorcyclist died due to the injuries he sustained in the crash. Deputies say he was identified as 20-year-old William Mchenry.
The driver of the car was taken to the hospital to be treated for minor injuries, according to deputies.
According to the sheriff’s office, during the investigation, deputies learned Mchenry was allegedly traveling at speeds of over 100 mph at the time of the crash.
The Wood County Sheriff’s Office, Wood County Crash Team, Parkersburg Police Department, Eastwood Volunteer Fire Department, Camden Clark Ambulance Service and Saint Joe Ambulance Service responded to the scene.

domain: news


High Reliability (Defense)
Military and aerospace applications require components with higher reliability than commerical applications.
These devices are specially designed to be robust in mission-critical applications, where commerical grade components may fail. “High-rel” components operate in harsh conditions such as high shock, high vibration, high moisture and extreme temperatures.
Thursday, July 23rd, 2015


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Edmund Searles writes that his conversion experience, from skeptic to faithful Christian, allowed him to appreciate the spirituality of the Baffin Island Inuit. His very personal religious odyssey started while he was doing field work for his dissertation in Iqaluit, Nunavut.
He and his then fiancé, now his wife, Mary Ellen Thomas, were living with an Inuit family. One day, the couple offered to take the three children of their hosts to a community swimming pool, as a way of showing their gratitude for their hospitality. The outing went awry, however. The author discovered that the young son of the family was scared, and was only willing to stand in the shallow end of the pool. He was afraid to get his face in the water. The author suggested that if the boy would cling to his back, he would swim around the pool and the child could ride around, safe from the water.
However, the boy became terrified when his face got dunked in the water, and he dug his fingers into Searles’ neck. The author immediately returned to the shallow water so the child could stand on his own and recover. Months later, after several additional outings to the pool, the author was discussing the boy’s phobia toward water with his mother. She mentioned that it was caused by the fact that he was named after the son of another Inuit who had drowned a year before he was born.
The author didn’t adequately follow up on the observation by the mother. He continued to analyze the boy’s fear in terms of the psychology of emotions and memories, and he mostly dismissed the mother’s ideas as so much folk theory. The notion that name-souls could move from one generation to another and carry their fears with them was alien.
But he describes, in this very personal narrative, how his fiancé, raised in a far more devout family than he was, completely accepted her Roman Catholic heritage. A budding anthropologist with a focus on the varieties of religious experiences, she decided to do her field work studying initiation rites among the Mandinga people of Guinea-Bissau. Searles went with her.
As he and his wife learned the local languages, they were exposed to people who were devoted to their Muslim faith, but who also believed in the presence of evil spirits, in the power of amulets to protect people against others, and in various initiation rites for children. They heard about shape shifters, about witches who ate souls, and about snake children who slithered in the forest. Their intense emotional experiences, and the faith of his wife, began to weaken his conviction that Christian faith is necessarily deviant.
He returned to the Episcopal church of his childhood and became much more open to the possibility that many puzzling aspects of the world cannot necessarily be analyzed solely in the context of materialistic forces or cognitive processes. His experiences in Guinea-Bissau enabled him, he explains, “to step outside my taken-for-granted view of the world and to learn why I refused to explore episodes of sorcery, prophecy, and reincarnation in the Arctic …” (p.171).
While he was in Nunavut, he had rejected the idea that the boy’s fear of water was due to his being reincarnated. The phobia should be explained in more rational terms. Now he was more willing to consider the possibility of such explanations.
Searles continues his essay by exploring the literature of naming practices among the Inuit. They believe that the souls of animals and people have three different parts. The tarniq is the part that gives health and life to the living animal. It can be persuaded to leave individuals by shamans. The loss of the tarniq results in death. When an individual dies, the tarniq leaves the body after a few days and may be reincarnated into another person. That is what may have happened when the other child died—his tarniq, along with the idiosyncrasies and memories of a fear of water, transferred to the newborn.
Another part of the soul is the inuusia, which provides breath and warmth to the person. The third spiritual entity, the inua, is the owner of objects. It is a spirit that controls the object’s destiny. The hunter is only successful if the inua of the prey is complicit in the act of hunting. If a hunter offends the inua of an animal he hunts through his inappropriate or deviant behavior, it will not cooperate and he will be unsuccessful.
These various spiritual entities tie the Inuit mystically to their past, present, and future, and they link them to their ancestors. The Inuit live in accord with the will of any inua that they may encounter, and they are bound by the name-souls that they are incarnated with. Inuit can be baptized into a Christian faith and still accept that they have name-souls. They may be connected with others through their own name-souls, but at the same time they accept the sacraments of their churches and a belief in Christianity.
The Inuit acceptance of name-souls and the reincarnation of deceased family members prompts them to be highly permissive parents. Adults rarely punish or even admonish their children—they believe that children are born with knowledge and characteristics that will gradually be revealed as they grow and develop. It would have been completely wrong for the family of the little boy with the fear of water to try and teach him to overcome his fears. His traits should be tolerated, perhaps valued, but certainly not judged based on psychological criteria developed by outsiders.
Searles closes his personal journey, cum explanation of Inuit name-souls, with the opinion that openness to varieties of religious beliefs and faith experiences can improve and illuminate anthropology.
Searles, Edmund. 2007. “Prophecy, Sorcery, and Reincarnation: Inuit Spirituality in the Age of Skepticism.” In Extraordinary Anthropology: Transformations in the Field, Edited by Jean-Guy A. Goulet and Bruce Granville Miller, p.158-182. Lincoln: University of Nebraska Press

domain: library


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Freeze Dried Chicken Liver
$11.88 Including GST
Made from 100% Australian Chicken Livers.
Liver is so beneficial for your furry friend. Having low calories and being high in protein.
Liver is a great source of protein and essential amino acids. A high-protein diet is important
for cats and dogs because they’re designed to burn protein as their main source of energy.
|24 × 16 × 3.3 cm

domain: pet


Welcome to Project Jacquard
Publication/Creation DateMay 29 2015
DescriptionProject Jacquard is a new system for weaving technology into fabric, transforming everyday objects, like clothes, into interactive surfaces. Project Jacquard will allow designers and developers to build connected, touch-sensitive textiles into their own products. This is just the beginning, and we're very excited to see what people will do with it.
Date archivedJune 1 2015
Last editedJuly 5 2021


More electrified than ever, Automobile Barcelona does not renounce passion and also allows you to look closely and admire some cars related to the world of competition. It should not be forgotten that the races, in their different modalities, are always excellent testing and research fields to subsequently apply improvements to street cars.
Cupra is a leading brand in this edition of Automobile Barcelona. The Tavascan and the Raval have taken center stage, but their two competition models are also on display. Designed for the racetrack, the UrbanRevel Racing Concept is a 100% electric vehicle that has racing in its genes. Its 100% electric propulsion system delivers 340 CV (250 kW) of continuous power and reaches a maximum power peak of 435 CV (320 kW). It accelerates from 0 to 100 km/h in 3.2 seconds.
The representation of Cupra among the competition cars is led by the spectacular single-seater that represents the Spanish brand in the Formula E ABB FIA World Championship. The ABT Cupra team competes in this benchmark electric competition, with two drivers, the Dutchman Robin Frijns and the Swiss Nico Müller.
One of the great attractions of Automobile Barcelona for rally fans is the presence of the QEV Zeroid X1: the model developed by the company QEV Technologies for the World Rally Championship in the electric RX2e category.
To verify its extraordinary performance, visitors can watch displays by professional drivers such as Pablo Suárez, official driver of the RX2e Championship with the Zeroid X1.
Ebro exhibits a 100% electric prototype, a light SUV with which it participated as a "zero car" in the 2022 edition of the Dakar Rally. Refounded as Ebro Automotive Corporation, Ebro returns to the market with a spectacular pick-up and the legendary Spanish brand does not hide its passion for competition.
Baptized as the Ebro SxS Dakar, it is a competition side-by-side format vehicle, it has a power of 150 kW (201 CV) and 390 Nm of maximum torque, with a range of 200 km, which is why Halfway through each stage, he had to change his batteries to complete the course.
Returning to the exciting rallies, Hyundai shows its weapons in the Superchampionship of Spain of the specialty. The Korean brand has a powerful team that participates behind the wheel of the spectacular Hyundai i20 N Rally2.
This vehicle is equipped with a 1.6-liter turbocharged engine combined with a five-speed sequential gearbox, this car has a power of the roads has a power close to 300 HP. Hyundai fights for victories and podiums in all the races and is currently the Spanish champion in the specialty, thanks to the team made up of Pepe López and Borja Rozada
Far from eradicating high-performance proposals, the irruption of electric cars creates the possibility of enjoying very powerful street cars. At Automobile Barcelona it is possible to see in detail a couple of high-performance models, such as the Baltasar Revolt, the BYD Seal and the Kia EV6 GT.
The Baltasar Revolt is the first model of the Barcelona company Baltasar Cars. It is a two-seater sports car with a totally radical approach. Made with ultralight materials, its total weight is 770 kg, its mechanics yield 500 CV of power and 1,000 Nm of torque and it is capable of accelerating from 0 to 100 km/h in 2.5 seconds. Its price is also exclusive, around 230,000 euros.
The BYD Seal is a 100% electric sedan that has a version equipped with two electric motors, one per axle, capable of offering a total combined power of 530 CV. Its acceleration capacity is enormous, going from 0 to 100 km/h in 3.8 seconds. This vehicle is equipped with a battery with a capacity of 82 kWh.
Another of the most surprising models, in terms of performance, is the new GT version of the Kia EV6 crossover. The propulsion system combines a shaft motor to achieve a combined power of 585 PS and a torque of 740 Nm. Its acceleration capacity is very brilliant, with a record from 0 to 100 km/h in 3.5 seconds and a top speed of 260 km/h.


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In addition to electing a new board of directors, the Council of Institutional Investors (CII) has named Florida State Board of Administration (SBA) Executive Director and CIO Ashbel “Ash” Williams as board chairman.
Williams, who has been with the $195.9 billion SBA since the late 2000s, was elected chair by the CII’s public fund members, as per association bylaws.
Board officers were also elected by CII, including co-chairs Mary Francis, who is corporate secretary and chief governance officer for Chevron Corp., and John Keenan, corporate governance analyst for the AFSCME Employees Pension Plan. Scott Zdrazil, senior investment officer—corporate governance, for the Los Angeles County Employees Retirement Association, is the treasurer. Cambria Allen, corporate governance director, UAW Retiree Medical Benefits Trust, was named secretary.
Francis and Zdrazil join Jerry Albright, CIO, Teacher Retirement System of Texas; Ron Baker, interim executive director, Colorado Public Employees’ Retirement Association; Renaye Manley, deputy director, strategic initiatives department, Service Employees International Union (SEIU); Thomas McIntyre, international representative, International Union of Bricklayers and Allied Craftworkers; Hope Mehlman, chief governance officer and assistant corporate secretary, Regions Financial; and Jennifer Peet, corporate governance director, Office of the Oregon Treasurer and Oregon Public Employees Retirement Fund, as new members of the CII board.
Existing board members Mary Collins, trustee, District of Columbia Retirement Board; Michael Garland, assistant comptroller, corporate governance and responsible investment, New York City Pension Funds; Aeisha Mastagni, portfolio manager, California State Teachers’ Retirement System (CalSTRS); and TerriJo Saarela, corporate governance director, State of Wisconsin Investment Board, have been elected as CII directors for the 2018-19 interim.
Last December, Williams was the honoree of CIO’s Industry Innovation Awards, where he received the Lifetime Achievement Award.
“If the team, culture, processes, and resources are right, the probability of investment outcomes that earn trust, enhance reputation, and build brand value is vastly enhanced,” he told CIO in December.
Williams could not be reached for comment.


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This is an elaborate treat that snuck past a lot of critics and potential audience when it was released back in 1995. The packaging for the CD came with some serious multimedia perks; certainly ahead of its time. The built-in CD-ROM features allow the listener/viewer the option of going through the whole disc with its own CD player software, occasionally alerting the viewer to videos where applicable. There are three altogether, but always available are some basic television images flashing on the computer screen plus controls to modify them (fast, slow, distorted, etc.). Lyrics are available to scroll down for each track, plus tour and contact information. Also present is a quick showcase of EBN's equipment, such as their impressive video image sampler as well as a demonstration of their absurd and amusing golf-bag rocket launcher. For buyers who didn't have a CD-ROM drive, never fear -- a floppy disc is also included in the sleeve to provide some basic multimedia wall of sound eye candy. But all of this is just visual. As for the music, this is a tremendously ambitious side project for Meat Beat Manifesto's frontman Jack Dangers, who seems like an ideal producer for this album, one that is so deeply rooted in found samples, TV clips, and soundbites. Using existing media as a prime source of material for much of this album, there are hardly any formal musicians in Emergency Broadcast Network, but rather a collective of producers, programmers, and audio/visual operators that create new works by utilizing a musicians' ear, if not a musical instrument. Two tracks feature a slightly more traditional approach: First visiting producer Brian Eno gives a little creepy breathing room for the track "Homicidal Schizophrenic," with guest guitarist Jamie West-Oram, ex-member of The Fixx. Also on the guest list is the ever-prolific Bill Laswell, who puts in his two cents for the track "Shoot the Mac-10," an inner-city tribute to a lightweight automatic weapon that features the surprisingly gritty rap skills of '80s legend Grandmaster Melle Mel, whose teeth have only sharpened over the years. As for the rest of the album, Dangers typically likes to stuff a record to the seams with soundbites and audio clips, and here he also adds commercial interruptions between several tracks. Telecommunication Breakdown is an almost overindulgent showcase for his style, but, due to the nature of this concept album, its excessiveness is what gives this album its wings. Not to be missed.
Emergency Broadcast Network
Telecommunication Breakdown Review
by Keir Langley


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CDC Admits as Many as 30 Million Americans Could be at Risk for Cancer Due to Polio Vaccine
Do vaccines cause cancer? Well Straight from the horses mouth, The CDC says it just may be so … but after 50 years they state more studies are needed (REALLY?).
The Centers for Disease Control and Prevention (CDC) posts on its own website the concern that as many as 30 million Americans could be at risk for cancer after receiving a Polio vaccination during the 1955 – 1963 time frame. This possibility exists because the vaccine in question was found to be contaminated with the SV40 virus. Most Americans received multiple doses of this vaccine that was administered to almost 100 million people.
Frequently Asked Questions about Cancer, Simian Virus 40 (SV40), and Polio Vaccine
SV40 is a virus found in some species of monkey. Soon after its discovery in 1960, SV40 was found in polio vaccine. More than 98 million Americans received one or more doses of polio vaccine during the period (1955–1963) when some of the vaccine was contaminated with SV40. SV40 has been found in certain types of human cancers, but it has not been determined that SV40 causes these cancers. The majority of evidence suggests there is no causal relationship between receipt of SV40-contaminated vaccine and cancer; however, some research results are conflicting and more studies are needed. For more information, see the fact sheet.
•What is SV40?
•Why is there so much interest in SV40?
•Does polio vaccine being given in the U.S. today contain SV40?
•What about concerns that the testing methods used to screen oral polio vaccines could have missed certain strains of SV40?
•Who received SV40-contaminated polio vaccine?
10–30 million of the 98 million people who received a polio shot actually received a vaccine that contained SV40
•Were any other people in the U.S. possibly exposed to SV40-contaminated vaccines?
•Is receiving contaminated vaccine the only way to become infected with SV40?
•SV40 is known to cause tumors in rodents. Have research studies found an association between SV40 and cancer in humans?
Yes. An association has been found between SV40 and certain types of cancer in humans.
•What steps have been taken by the government to see if SV40-contaminated vaccines affected people’s health?
•What has research found regarding the health effects of receiving SV40-contaminated vaccine?
•Have research studies looked at the risk of cancer in children whose mothers received SV40-contaminated polio vaccine?
•If I have one of these cancers, does it mean that SV40 caused it?
•Can I obtain a test to see if I am infected with SV40?
•What should I do if I received polio vaccine during 1955–1963?
•Where can I get more information about SV40?


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I will stop drinking and smoking – Peruzzi mourns Obama DMW, narrates his last moments before death (Photo)
The death of one of Davido’s aides, Habeeb Uthman (popularly known as Obama DMW) has sent jitters down the spines of the singer’s fans and concerned Nigerians.
Obama DMW reportedly died, June 29, at Ever-care hospital in Admiralty Way, Lagos. It was also reported that he was hale and hearty in the last moments before his death as he drove himself to get medical attention after experiencing breathing difficulties.
In a screenshot of a conversation between DMW act, Perruzi, and an unknown person, it was noted that Obama DMW was in the company of other crew members hanging out with Davido in the studio before his scheduled travel out of the country.
Peruzzi who was clearly in a state of utter shock made it known that Obama’s probable cause of death was the unsavoury lifestyle of smoking and drinking which he vowed to stop taking.
See the chat below:
Davido, however, is yet to react to the sad news as his last social media post was made 14hrs ago, showing him on a flight to an unknown location.


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Separate names with a comma.
Discussion in 'Pennsylvania' started by 6922design, May 9, 2014.
Picked 7 dog peckers in York County last night. Cant wait to find more tonight and this weekend!
Hi im new to hunting and im in York County in the Red Lion /Windsor area can you give me any hunting tips and good areas to start hunting . My mom loves them and I wold love to find her some . Thanks for any help you can give .

domain: hobby


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EXPO AND KOSHER FOOD: BUSINESS OPPORTUNITIES
- Published: Friday, 29 May 2015 11:51
Remy Cohen participated at the intenational conference on the kosher food and business opportunities arising from the Milan Expo 2015. The main focus was the issue of certification in food processing and transparency of public works.
Read the full article

domain: food


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Remonte is the sister company of the Rieker group.
With a history dating back more than a century, the Swiss-German Remonte footwear company remains a leading producer of uniquely comfortable and glamorous women's shoes, sandals and boots. Holding true to the company principles of quality craftsmanship and great value, Remonte clearly show why high-caliber materials and foot supporting construction form a priceless combination.
The characteristics and components that go into the manufacturing of the Remonte footwear are the same as sister company Rieker.
1. A unique construction method involving specially designed components gives the footwear a light feel.
2. The last shapes help to prevent forward moving of the foot which gives your feet freedom during the day.
A Selection of our Spring/Summer Styles

domain: design


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Encouraged by the wind forecast for the second day of the Rollei Summer Openings presented by Volkswagen Nutzfahrzeuge, the many visitors and participants anticipated a spectacular slalom day. In bright sunshine, tens of thousands of windsurfing enthusiasts gathered on the promenade of Westerland. Unfortunately, the wind did not live up to its promise and forced the windsurfing elite again to be on hold.
Around 10:00 clock, whilst the wind was still at its best, the Race Committee prepared for the slalom discipline. But after the first heat the competitors were sent ashore. Heavy sea fog affected visibility for sailors and racing crew so badly that for security reasons racing had to be stopped, and then the wind fell under the minimum required for slalom.
After a short break to re-organise themselves, the race committee moved to the light wind discipline of racing (Formula Windsurfing). Equipped with sails up to 12 square meters, the racers gathered at the starting line, only to be thwarted by this fickle wind as the race was abandoned. Thus, the second day of competition saw no contest.
While the 63 participants used the forced break for intensive discussion of interesting subjects such as new equipment and past training sessions, the numerous visitors, meanwhile, enjoyed the sun and the rich offerings of the food outlets and the shopping district of Westerland Promenade.
The wind and weather forecast for Friday's race day shows wind speeds force 6-7 and thus ideal conditions for the slalom discipline. So then the first rounds of the slalom World Cup can be completed hopefully.
Maybe it's enough for the wave riding discipline? The first race expected to be launched Friday at 10.15.

domain: sports


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I made this functional wine barrel costume for halloween 2012. Wine is gravity fed from a camelbak out the spigot in front.
- Camelbak + backpack (reusable after)
- faux-wood flooring
- Thin wood strips (mine were ~1x0.25)
- Small pieces of wood quarter round
- Metal strapping with holes
- Small bolts and nuts
- Vinyl tubing (sized to fit tightly over your camelbak hose)
- Barbed to NPT adapter
- 90 degree female-female NPT
- Small NPT spigot with male NPT end
- Large washer (should fit over the male end of the spigot but not past it)
- 1/4" rope
- Drill + bits
- Wood glue
- Small crescent wrench
- Normal crescent wrench
- Teflon pipe tape
- Exacto knife
- Spray Paint
- Duct tape
Step 1: Inner Frame
Determine the the size of the frame for your barrel (this will define the diameter). The frame should be a rectangle slightly larger than your torso as measure from a few inches under your armpits. Make sure the frame is large enough that it will slide down over your body with your arms above your head (at the diagonal).
Cut your thin strips of wood to size. Cut small pieces of quarter round (or similar) to act as corner braces. Assemble the frame using glue and carefully staple the corners for extra strength. You will need to use clamps to hold the frame tight while the glue dries. It's challenging to get the frame to hold a nice rectangle under clamping force. I found it helpful to form two "L" shaped sections, let them dry, and then assemble into the rectangle.


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Boost of £2million for youth mental health services in Suffolk
- Credit: PA
Mental health services for children and young people in Suffolk have received a financial boost of £2million.
The governing bodies of NHS Ipswich and East Suffolk and NHS West Suffolk clinical commissioning groups (CCGs) have decided to increase funding following a rise in demand for mental health services in the region.
Money will be used to recruit additional mental health professionals to improve waiting times, access to treatment and ongoing support.
The Children and Adolescent Mental Health Service will be expanded with more clinical staff offering a broader range of mental health expertise and support for evidence-based interventions and treatment.
Services for those who are known to social care, more likely to present themselves for care at hospitals and are more likely to be involved in the social justice system will also be bolstered.
Chief executive of Norfolk and Suffolk NHS Foundation Trust, Stuart Richardson said: "We welcome this additional investment, which recognises that these vital services require further support in order to provide the best possible care for children and young people."


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Germany has tightened the mask regulations on COVID
On Wednesday in Berlin, the cabinet of German Chancellor Olaf Schulz passed legislation to ensure that the fundamental safeguards against the coronavirus pandemic will remain in place during the fall and winter, when it is anticipated that there will be an increase in the number of cases of the virus.
In accordance with the new regulations, passengers on long-distance transportation by train, automobile, or airplane are now required to wear N95 respirators. During this time, photographs were published showing German Chancellor Angela Merkel and Economy Minister Robert Habeck travelling to Canada without wearing face masks earlier this week.
How to Put On A N95 Mask Properly? The CDC recommends, when particulate respirators are needed, that one of the following NIOSH-approved particulate respirators be worn: N95, N100, R100, or P100 (Note that the R designation does not mean respirator. These particulate respirators are called R series to designate their filter class and not because they are respirator types of respirators.)
When it comes to keeping yourself and your family safe during flu season, N95 masks are your first line of defense. These masks are designed to prevent the spread of germs like the influenza virus by preventing them from getting into your body through your mouth or nose. However, these masks only work when you put them on correctly, which means it’s important to know how to put on an N95 mask properly so that you can ensure maximum protection from the flu season ahead. Check out this article from Brianne Smith to learn how to put on an N95 mask properly and keep yourself protected this winter!
Filtering N95 Masks Harley L-188 Respirator – N95 Face Masks (n95-face-mask.com)
11 thoughts on “Germany has tightened the mask regulations on COVID for travel throughout the fall and winter seasons.”
Wow, this was much cooler than I expected it to be! Big props.
This is an awesome article. really well done. Remember P100 masks are over 166 times better than N95. Why healthcare authorities never talk about P100 respirators
I hope this is working lol
I really find this thorough and informative, but I have a question because of another post I have seen from an OSHA 10&30 certified person. Whether that is true or not, they brought up that N95 masks are originally made to wear in a contaminated environment
fascinating!! thanks for all the hardwork put into researching, writing this!
Very thorough, scientific information, good close ups, and real use feedback.
Thanks for taking the time to post this article.
Thank you for such an amazing explanations
Best explanation ive gotten about n95 for now thanks so much
Technically, you could cycle between 3 to 4 masks for Covid proof re-usability. Although healthcare workers might also need to change masks more frequently. Brilliant article as always!
Extremely valuable information. Thank You.


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Is it time for Nationals to panic?
You know what they say about the definition of insanity: it’s creating a weekly sports-radio segment featuring a second-or-possibly-third-string NFL quarterback in a major media market.
No wait! That’s not it! Insanity, they say, is watching your powerhouse baseball team struggle for a solid month, fall out of first place, and teeter on the edge of disaster without reckoning that a few changes — or at least raised voices — might be in order.
“What do you do? You move on,” Nats Manager Matt Williams placidly told the Junkies this week, when discussing his flailing team, now 10-16 since the all-star break, the sixth-worst mark in the league.
“We have to be positive and move forward,” Williams also said. “It hasn’t worked out since the break the way we wanted it to, but that doesn’t mean it can’t turn.”
Look, he’s probably correct. If Williams panicked and started mashing buttons — Ryan Zimmerman to the leadoff spot! Joe Ross to the bullpen! Calvin Coolidge to the President’s Race! — critics would slam him for freaking out, for flailing, for losing control, for not trusting that his talent will win out in the end.
Still, it’s kind of unsettling when the public stance of leadership remains stately reserve, even as the peasants are lighting their clothes on fire and beheading their chickens (and their chia pets).
“I feel like y’all are the only ones worried about us,” Anthony Rendon told reporters early Wednesday morning, apparently having boycotted Twitter, Facebook, sports radio, the office cooler, the Nats Journal comment section and the “playoff odds” section of every baseball site. “Don’t worry about us. Y’all worry about y’all selves.”
“I don’t mind being in stalking position,” Jayson Werth told Yahoo’s Tim Brown this week, essentially advocating for second place over first. “When you make the run at it down the stretch, it’s easier to chase than to be chased.”
Well, maybe. But even if it’s just for show, it feels like some changes might be reassuring, before “stalking position” becomes “prone and lifeless position.” Herewith, a few suggestions.
1. Move Werth down: Werth increasingly reminds me of my favorite 19th century Russian novelists, and not just because of his Dostoevskian beard: they’re depressing, they offer constant reminders of our own mortality, and yet they remain wildly popular.
Werth’s OPS is now .535. Of the 299 Major League players with at least 175 plate appearances this season, that ranks 297th. That’s bad for a reserve; it’s catastrophic for an everyday, middle-of-the-lineup bat.
My Internet pal Harper Gordek — the Boswell of Nats bloggers, except with skepticism instead of optimism — just wrote the definitive piece on the Werth Question. You probably can’t bench him — because of his contract, his leadership role and the fact that a true Werth resurgence would be far more valuable than whatever you can hope for from Clint Robinson. But that doesn’t mean he needs to bat fifth.
“If you truly think he needs to work his way back and that’s all, it shouldn’t matter if he’s batting 4th or 5th or 9th,” Gordek wrote. “It’ll happen. In the meantime, if it’s not happening, he’s not stranding runners again and again.”
2. Start treating big games like big games: Remember when the Nats played six games against the Mets and Max Scherzer didn’t pitch at all?
“We saw all three of their horses twice in the matter of two weeks,” Bryce Harper said then. “They haven’t seen Scherzer since Day 1.”
This was true. But the thing is, the Nats pitching rotation wasn’t being decided by a mindless flesh-eating demonic overlord. It was being set by Williams, the manager, who rather easily could have jiggled the rotation around the all-star break to ensure at least one Scherzer appearance against the Mets. And that’s not even mentioning the way Drew Storen and Jonathan Papelbon sat out the second series with the Mets, a three-game sweep that set the stage for the current problems.
Is there an element of panic when you mess with your rotation to match up with a division rival in August or even July? Sure. Is it worth it to make sure your best players are actually on the field for your most important games during a divisional race in a crucial season? Yeah, probably.
“Williams declined to line up his rotation so that Max Scherzer would face the Mets in either of two series after the break, then failed to use either of his top two relievers, Drew Storen and Jonathan Papelbon, while getting swept in a closely contested three-game series at Citi Field,” Ken Rosenthal noted this week. “Greater urgency seemed warranted.”
That’s one way of putting it. The Nats have six games left against the Mets, games that figure to virtually decide the division race. It’d be nice to see Scherzer, Storen and Papelbon on the mound during those games.
3. Get flexible in the bullpen: Eighth-inning man Storen’s recent struggles in the eighth inning provide an opening for Williams to take a few more liberties with his bullpen, using his best pitchers in the most important spots, and therefore not saving Papelbon exclusively for save opportunities.
As I write this, Papelbon has pitched three innings in the month of August. That’s less work than Matt Thornton, about the same amount of work as Casey Janssen, and far less work than Storen.
Papelbon was the big July acquisition, the last piece to push this team over the edge. He can’t push from the bench.
And for all we’ve heard about relief pitchers doing best when they know their role, Storen knowing he will appear in the eighth hasn’t prevented his recent problems. So maybe don’t worry as much about who has which role moving forward.
4. Panic!: OK, not really. This last thing is purely superficial, and possibly unfair. But that urgency Rosenthal is looking for could maybe translate into a new vocabulary, reflecting the fact that one of the preseason World Series favorites is now in a battle just to remain within striking distance of the playoffs.
We’ve already heard “Where’s my ring?” and “how can we lose?” and “the best team in baseball” and “it’s our division to lose.” Maybe it’s time for some similarly memorable quotes about the seriousness of Washington’s current predicament, or a few smashed clubhouse fruit trays, anyhow.
Ripping out your chest hair won’t help in the standings. But it wouldn’t be the most insane thing in the world.


The Autonomous Bougainville Government is set to trial a new mobile phone awareness platform to provide people up to date information on the referendum and Peace Agreement.
For eight weeks starting September 22nd, Digicel users across Bougainville will receive an automated call from the ABG BPA Hotline with a recorded message from the ABG President, Chief Dr John Momis.
A number will then be provided for people to call and hear pre-recorded audio messages – and it is free.
Acting Chief Secretary Thomas Raivet said people have told government that they want information to be given out through their mobile phones.
“A recent Bougainville audience survey found that more people have access to a mobile phone than radio, newspaper or TV. That’s why we are trialling this new mobile phone awareness to prepare our people for referendum and beyond,” said Raivet.
ABG Media and Communications Director, Adriana Schmidt, said the service is being trialled for the first time in Bougainville and urged all who have access to mobile phones to utilise this free information service.
“Calling this number is free, and will give you a choice of four different audio messages on Peacebuilding, Autonomy, Weapons Disposal and Referendum. We want to ensure people have access to approved government information,” she said.
The information is based on the Joint Referendum Key Messages agreed to by both governments in June 2018.
The recent Bougainville Audience Study found that across Bougainville, three out of every four adults had access to a mobile phone, with equal numbers in north, central and south regions. However, credit was a key issue for phone users and so with the support of development partners, the ABG is making the ABG BPA Hotline a free service.
The referendum awareness initiative is supported by the Australian and New Zealand governments in partnership with the Autonomous Bougainville Government and the Government of Papua New Guinea.


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You’ve got to love anyone who, for her birthday, give you a gift. Say Happy Birthday to J.C. Hannigan and get her books for free or on the cheap.
❣ COLLIDE SERIES SALE! ❣
The entire COLLIDE series is on sale! Grab all three books for under $2!
“I am so in love with this series. I have become emotionally attached to Harlow, Jax, Iain, Jenna, and Crimson. This is one of those series that just stays with you.” – Reviews By Reds (Dusty)
✴ COLLIDE (The Collide Series Book 1) ✴
🌠 🌠 🌠 #FREE! 🌠 🌠 🌠
Harlow Jones has a troubled past, and a questionable future. Surrounded by death, tragedy, and intrigue, she is forced to mature long before her time. Plagued by anxiety and depression, she hides her inner turmoil with spite and sarcasm. Her thick skin is impenetrable…or so she thought. Until she becomes involved with her grade twelve English teacher. In this exclusive entry into the new adult genre, with raw style that is as dark as it is poignant, Collide presents the ultimate choice: forbidden love or doing the right thing.
✴ CONSUMED (The Collide Series Book 2) ✴
🌠 🌠 🌠 #99cents! 🌠 🌠 🌠
Jax Walker is a hard man to resist. He’s tall, dark, and delicious. Harlow didn’t plan on falling for another, with her heart still stuck on Iain. But it’s so hard with him gone. And she’s been aching since they last touched. Two whole years of silent wondering; of desperate sleepless longing. Fate, however, may have other plans. Just as Harlow’s ready to open herself to new love, her whole world is pulled into a twisting and painful spiral.
In this new adult novel, readers are consumed by the collision of past and present. Raw and dark, this emotional minefield is the perfect second book in the continuing story of Harlow Jones.
✴ COLLATERAL (The Collide Series Book 3) ✴
🌠 🌠 🌠 #99cents! 🌠 🌠 🌠
As the scars on Harlow’s body slowly fade, the ones etched into her soul take longer to heal. Harlow faces her biggest challenges yet, as she navigates the trauma of being attacked in her home, the struggle of trying to move on with her love life, and a dark secret that could destroy her most enduring friendship.
This new adult novel is the darkly satisfying third installment of the Collide series. Here, Harlow Jones is at her most raw, as she finally faces her demons, and Iain Bentley, head on.