text:
Rishabh Pant and Hanuma Vihari put themselves in the reckoning for next week's first Test with contrasting hundreds as India thoroughly dominated Australia A on Day 2 of the day-night practice match, in Sydney, on Saturday.
Needing 19 runs to reach his century, Pant clobbered Jack Wildermuth for 4, 4, 6, 4, 4 off the final over of the second day, to finish unbeaten on a blistering 103 off only 73 balls, inclusive of six sixes and nine fours.
At the other end, Vihari stroked a solid 104 off 194 balls as India reached 386 for four at stumps on the second days, for an overall lead of 472 runs.
Also staking a claim for selection is young Shubman Gill, with an elegant 65 off 78 balls, laced 10 sweetly-timed boundaries.
In the final session of play, Pant's aggressive approach paid dividends as he smashed the Australia A bowlers to all corners of the Sydney Cricket Ground, the southpaw making a strong case for himself for the wicketkeeper's job in Adelaide ahead of Test specialist Wriddhiman Saha.
It has been a superb turnaround from India, who were bowled out for 194 on Day 1, which would have been far less if not for pace spearhead Jasprit Bumrah's maiden first-class fifty, before the visitors staged a strong comeback with both bat and ball.
While Gill may have booked himself one of the opening slots with his dazzling strokes, Hanuma's effort might force the Indian team to play an additional batsman in the series opener.
Coming out to bat again in the beginning of the day's play, India lost Prithvi Shaw in the second over as the young right-hander perished for three.
If Shaw missed out on an opportunity to make a big score in good batting conditions, his contemporary Gill grabbed it with both hands on the way to reaching his half-century off 49 balls.
During his stay in the middle, Gill played some elegant drives and looked assured while going on to the backfoot, which seems to be his forte.
However, the 21-year-old got out in an unfortunate manner to leg-spinner Michell Swepson, giving caught off an inside edge by Sean Abbott at first slip, who dived full length to his length to take it inches from the ground.
TV replays were inconclusive and the absence of DRS and Snickometer in the practice game, a disappointed Gill had no option but to walk back to the dressing room as umpire's decision could not be challenged.
That ended a 104-run partnership for the second wicket between Gill and Agarwal, who was joined in by Vihari for another half-century stand.
Thereafter, the duo of Vihari and skipper Ajinkya Rahane was involved in a partnership of 78 runs for the fourth wicket as the Australian bowlers toiled hard for wickets.
There was a brief rain interruption after Pant walked in at the fall of Rahane's wicket but he straightaway played his shots to further unsettle the Australian bowlers.
Even as Vihari showed great composure and patience in collecting his runs, Pant was quite at ease while clearing the fence, reaching his fifty with a cracking square cut in just 43 balls.
Pant continued in same vein till the end of the day's play and hurtled towards his century with a flurry of big hits. While Vihari, in all, struck 13 boundaries.

domain: sports


text:
Roulette is one of the most critical and accessed casino game. It would be a table and cards game if we were to say it correctly. The players must guess the number and the color on which the ball will end up. This is not only a luck game. It's all about strategy and quick thinking.
What comes into your mind when thinking about Argentina? The lush green pampas fields? The wild horses? How about Evita Peron who fought tirelessly to rally for her husband election's victory. The Argentinians could enjoy Gratorama that is online gambling that promises punters 100% from the initial €200 bet money.

domain: game


text:
Well, we've been off to the races for a while now, and depression is not quite the right word, but I can't be the only one with less passion, focus and energy for this election than I had a couple of months ago. I'm sure part of it is simply a natural withdrawal from the drama of the primaries on both sides; part of it relief at the departure of the Clintons; part just exhaustion from a period of intense focus.
But something else hovers. In trying to tease out the roots of my own ennui, it occurred to me last night that one reason is that one key, expressive aspect of this election is already over. We will not elect another Bush, or his appointed successor, or someone closely allied to him in certain key areas - climate, torture, full-throated conservative Christianism, reckless war-making. The electorate has already purged this legacy from the system, in so far as it can with an incumbent still-president.
Among the Republicans, it is easy to forget that there were several viable candidates who were utterly unapologetic about the Iraq war, who favored torture and detention policies indistinguishable from Cheney-Bush (or worse), who intended to run either as an even less restrained executive (Romney, Giuliani), or as an even less moderate Christianist (Romney, Huckabee). On the Democratic side, the rejection of the Clintons, with all their baggage, all their capacity to jump-start the culture wars, and all their unending '90s psychodrama was also an enormous, and by no means inevitable, step forward - and away from the worst of the past.
So in many respects, the vital expressive work of this election is already done; and the electorate has already spoken. By nominating Obama - the antithesis of Bush - and McCain - Bush's former defeated rival, the Bush-Rove era is already over in the deepest sense. If we had an incumbent Bush vice-president - or a Romney or Giuliani on the ticket - it would feel a lot different. Now, we have the more palatable choice of the post-Bush or the really un-Bush. No wonder a sense of relative relief.
The big gap in this argument, of course, is the war.
The greatest question in my mind is whether McCain is actually even more interventionist and neoconservative than Bush - just more focused on competent execution and moral decency - or whether he is a more realist and responsible commander-in-chief than the one we now have. Does he still see Iraq as a beach-head for the new American century, or does he really want to get us out of there as soon as he can? I see signs of both, but mostly, recently, of the former. When you're this close to Lieberman, have neocon fanatics like Michael Goldfarb as a spokesman, and speak in the Bushian bromides of "victory" and "surrender", it's hard to feel reassured that the worst pathologies of the last seven years have been driven from the system. McCain in this sense represents a lingering and deluded notion that the war in Iraq was worth it - or will be worth it, once the execution is improved, and the original concept rescued and vindicated. Obama represents a more decisive rejection of the whole argument for the war, with its notion of constantly expanding American control of the planet as a solution to terror, adoption of pre-emptive conflict, and long-term occupation of and enmeshment with the Arab Middle East.
The other less gripping question is the economy, where McCain's commitment to the permanence of Bush's tax cuts does indeed represent a third term - especially without any serious attempts to cut entitlements or defense. (The pork-buster routine is a trivial side-show in terms of real government spending.) But, to me at least, there's almost as much economic risk in Obama's tax hikes and expensive healthcare plan. I say almost because at this point in our indebtedness, the candidate who deepens the deficit less should get the benefit of the doubt. So far, that looks like Obama.
This is a real choice, then, between a reconstructed Bushism and a thorough rejection of it. But it is not the choice the electorate had four years ago, or even two years ago. That threat has receded. For which we can give a certain amount of thanks to the wisdom of the voters so far.
(Photo: Peter McDiarmid/Getty.)
We want to hear what you think about this article. Submit a letter to the editor or write to firstname.lastname@example.org.

domain: politics


Results tagged “Afghanistan”
Would you like to limit the tag results display to a specific section?
If you do, then pick any of the sections below:
Or simply go to the aggregated tag results from:
The Taliban killed seven children in an IED attack in Paktika and four civilians in bombings in Zabul and Kandahar. Security forces killed 10 Taliban fighters. The Afghan government is reportedly still balking over the language of the Bilateral Security Agreement with the US.
A suicide bomber killed two policemen in an attack on a checkpoint in Ghazni. The Taliban killed two more civilians in an IED attack in Helmand. Jalaluddin Haqqani eulogized his son, Nasiruddin. The US canceled a purchase of Russian helicopters for the Afghan Air Force.
The Taliban killed three students in a bombing in Farah and an ISAF soldier in an IED attack in the south. The US transferred FOB Salerno in Khost to Afghan forces. The UN said the poppy harvest has increased by 36% since last year.
Nasiruddin Haqqani, a top leader in the Haqqani Network, was gunned down in Islamabad, Pakistan. The Ministry of Interior claimed that 28 Taliban fighters were killed during operations throughout the country. Tribal leaders and clerics oppose the Bilateral Security Agreement with the US.
Security forces killed 18 "rebels" in airstrikes in Zabul, five more in Helmand. The Ministry of Defense rejected a US military report that claimed casualties suffered by Afghan National Security Forces have risen by 79% over the past year.


Say hello to the airbrushed version of you. Perfect for hot studios, hard classes & everywhere else! Made with a second-skin fit & feel, Airlift fabric sculpts and lifts like no other. You'll love them and live in them. Plus, a higher waistband is shaping and pairs well with cropped tops & cute bras.
- Lifts & sculpts!
- Breathable & moisture-wicking — a hot yoga fave!
- Designed & uniquely fit to flatter every size
- Signature, micro-performance, double-knit Airlift fabric
- 4-Way stretch for a move-with-you feel
- Front-smoothing panel for commando comfort
- Wash separately, by hand, in cold water. Lay flat to dry. Low iron. Do not dry clean.
- High rise & hits at mid-calf
- Model 1 is 5’10”, with a 24” waist & 34.5” hips — she wears size XS. Model 2 is 5’9”, with a 34” waist & 43” hips — she wears size L.


text:
Funder Spotlight: BD Joins the Road for Good Health
Global medical technology company BD has long included Zufall Health in its philanthropic endeavors. In its most recent contribution, BD has committed $150,000 in funding to Zufall’s mobile medical unit replacement campaign.
SVP of External Affairs and Zufall Health Foundation Director Shade Cronan expressed gratitude: “We appreciate BD for bringing us closer to securing a new mobile medical unit. BD’s generosity is critical to breaking barriers in health care access and transforming lives, particularly for people who cannot easily reach a Zufall site.”
Cronan added that the new vehicle’s exterior will feature BD branding. “The new mobile unit, like the existing one, will regularly visit schools, farms, senior residences, food banks, and other community spaces. The BD name and logo will be visible on the outside of this doctor’s office on wheels.”
Zufall’s relationship with BD dates to its receipt of the inaugural “BD Helping Build Healthy Communities Award” award in 2013. This game-changing donation from BD not only elevated Zufall’s capabilities in diabetes care but helped the health center engage on the national level.
BD has also provided significant funding to ÁNDALE, Zufall’s nutrition and fitness program for children with obesity, among other initiatives. Given BD’s history of thoughtful and generous support for innovative patient programs, asking BD to take a lead philanthropic role in the mobile unit’s replacement made sense, Cronan said.
BD is enthusiastic about the vehicle as the latest development in its partnership with Zufall. Sien Avalos, Director, Social Investing & Vice President for the BD Foundation, said, “BD is proud to support Zufall Health in their mission to provide access to quality, affordable health care to people and communities who experience barriers to care. Our pledge supports a new mobile medical unit that delivers care to our New Jersey neighbors and furthers our company’s driving purpose which is to advance the world of health. We congratulate Zufall Health on their innovative approach to expand access to those patients who need it most.”

domain: news


The Blue Bulls Women got their SA Rugby Women’s Premier Division campaign off to a flying start as they defeated defending champions, Border Women, 12-0 at Loftus Versfeld on Saturday.
It was always going to be a tough match between two quality sides, and the match lived up to expectation as both teams gave as good as they got from early on in the match with both defences keeping strong.
It was the home side that got the first points of the day when winger Lynn Subke barged her way over the try line in the 10th minute of the match. Flyhalf, Elizabeth Janse van Rensburg, added two points with the conversion, and this was enough to give the Blue Bulls Women a 7-0 lead at the halfway mark.
Once again, the home side started well in the second half with Subke again crossing over the tryline in the 45th minute.
Janse van Rensburg then added another three points when she kicked over a penalty in the 51st minute of the game.
The Blue Bulls Women held on to their 12-0 lead until the final whistle to claim a victory in their season-opening match.
The Tshwane-based side will next face the Eastern Province Queens in a clash in the coastal town of Port Elizabeth on May 7.
Blue Bulls Women (7) 12
TRIES: Lynn Subke (2)
CONVERSION: Elizabeth Janse van Rensburg
PENALTY: Janse van Rensburg
Border Women (0) 0


text:
Targeting of the AXL receptor tyrosine kinase by small molecule inhibitor leads to AXL cell surface accumulation by impairing the ubiquitin-dependent receptor degradation
Overexpression of AXL receptor tyrosine kinase (AXL) in various human cancers correlates with reduced patients overall survival and resistance to first line therapies. Therefore, several AXL tyrosine kinase inhibitors (TKIs) are currently under clinical evaluation.
AXL TKI BMS777607 treatment increased AXL protein levels after 24 h as observed by Western blot and flow cytometry analysis. Mechanistically, this inhibition-induced AXL cell surface accumulation was neither associated with epigenetic modifications, nor altered transcriptional and translational regulation. Further, we saw no impact on glycosylation and receptor shedding by α-secretases. However, we observed that BMS777607 increased the glycosylated 140 kDa AXL protein abundance, which was impaired in the kinase dead mutant AXL (K567R). We demonstrated that AXL kinase activity and subsequent kinase phosphorylation is necessary for GAS6-dependent receptor internalization and degradation. Blocking of kinase function by BMS777607 resulted in ubiquitination prohibition, impaired internalization and subsequent cell surface accumulation. Subsequently, AXL cell surface accumulation was accompanied by increased proliferation of 3D-Speroids induced by low μM levels of BMS777607 treatment.
Our data suggest a re-evaluation of anti-AXL clinical protocols due to possible feedback loops and resistance formation to targeted AXL therapy. An alternative strategy to circumvent feedback loops for AXL targeting therapies may exist in linkage of AXL TKIs to a degradation machinery recruiting unit, as already demonstrated with PROTACs for EGFR, HER2, and c-Met. This might result in a sustained inhibition and depletion of the AXL from tumor cell surface and enhance the efficacy of targeted anti-AXL therapies in the clinic.
KeywordsRTK AXL TKI Ubiquitin Degradation 3D spheroid
A Disintegrin and Metalloproteinase Domain
RAC-α serine/threonine protein kinase
AP-1 transcription factor subunit
AXL receptor tyrosine kinase
- BMS (BMS777607)
Castias B-lineage lymphoma
MET proto-oncogene, receptor tyrosine kinase
N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester
Epidermal growth factor receptor
eukaryotic translation initiation factor 4B
eukaryotic translation initiation factor 4E
Extracellular signal-regulated kinase
Fetal calf serum
Growth arrest specific gene 6
Growth factor receptor bound protein 2
erb-b2 receptor tyrosine kinase
Hypoxia inducible factor 1 subunit alpha
the nuclear factor-kappa B
p38 mitogen-activated protein kinase
Proteolysis targeting chimera
Receptor tyrosine kinase
Reverse transcription-quantitative PCR
Standard error of the mean
Sp1 transcription factor
Signal transducer and activator of transcription signaling
Tyrosine kinase inhibitors
Deregulated oncogenic activity of the AXL receptor tyrosine kinase (AXL) and elevated levels of its ligand GAS6 (growth arrest specific gene 6) are found in numerous types of human cancer and are directly correlated with diverse aspects of cancer pathogenesis . AXL up-regulation has also been described in cisplatin-resistant ovarian cancer, doxorubicin-resistant acute myeloid leukemia, lapatinib-resistant breast cancer, imatinib-resistant gastrointestinal stromal tumors, and imatinib-resistant chronic myeloid leukemia. Recently, AXL activation has been reported as a cause of resistance to epidermal growth factor receptor (EGFR)-targeted therapy in non–small cell lung cancers [2, 3].
AXL expression is regulated via various mechanisms. It is subject to epigenetic modifications, i.e. DNA methylation and histone acetylation . Hypomethylation of the AXL gene has been associated with high expression in different cancer entities. Multiple transcription factors, including SP1, AP-1 and HIFα, can induce AXL transcription [5, 6]. Expression of splice variants is regulated post-transcriptionally and by translation initiation factors, e.g. eIF4E and eIF4B . AXL undergoes either N-linked or O-linked glycosylation in the Golgi apparatus before it is properly recruited to the membrane [8, 9]. AXL kinase activity is increased after GAS6 binding leading to activation of downstream signaling cascades . AXL signaling stimulates phosphatidylinositide 3-kinase/RAC-α serine/threonine protein kinase (PI3K/AKT), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase cascades (MAPK), the nuclear factor-kappa B (NF-κB) pathway as well as signal transducer and activator of transcription signaling (STAT) . Therefore, biological processes including invasion, angiogenesis, resistance to chemotherapeutics and targeted drugs, survival, and proliferation, as well as receptor downregulation are tightly regulated. Phosphorylated AXL is internalized for subsequent degradation or recycling via proteasomal, lysosomal or endosomal pathways [11, 12, 13]. Since deregulated AXL expression is associated with cancer and other pathological conditions, a better understanding of AXL regulation is critical for AXL-targeted treatment approaches. A complex of γ-carboxylated GAS6 Ca2+-dependently bound to phospholipid PtdSer causes homo-dimerization of the receptor, leading to the optimal activation of AXL kinase by phosphorylation of tyrosine residues at the receptor C-terminal kinase domain. This phosphorylation event creates docking sites for AXL downstream signaling molecules [14, 15]. In parallel, AXL phosphorylation leads to recruitment of the GRB2 adaptor protein, which recruits the E3 ubiquitin-protein ligase CBL in similar fashion as shown for c-MET [16, 17]. An additional mechanism is the direct recruitment and activation of CBL through the CBL tyrosine kinase binding (TKB) domain. Upon binding and activation of CBL, AXL is ubiquitinated . This posttranslational modification is required for efficient AXL degradation in the lysosome . An alternative pathway of AXL degradation is the proteolytic shedding by ADAM10 and ADAM17, as described by Miller et al., releasing a soluble 85 kDa N-terminal fragment (sAXL) and a short intracellular 55 kDa C-terminal fragment . This soluble sAXL receptor can be used as a biomarker and companion diagnostic tool as shown for hepatocellular carcinoma (HCC) and malignant peripheral nerve sheath tumors (MPNST) [20, 21]. Because AXL is considered an important molecular target in cancer therapy, various strategies, like sAXL decoy receptor (GL2I.T and MYD1–72) and antagonistic monoclonal antibody targeting AXL (YW327.6S2 and 20G7-D9) are currently in preclinical development. Other applications have already proceeded to clinical trials . Among the most promising AXL-inhibitory approaches are small molecule tyrosine kinase inhibitors (TKIs). In the present study we used the preclinical AXL/MET small molecule inhibitor BMS777607 (BMS) . Here we show that AXL inhibition by BMS causes accumulation of the AXL receptor on the cellular surface due to impaired receptor downregulation. We propose that inhibition of AXL kinase phosphorylation by the small molecule inhibitors causes reduced ubiquitination of AXL leading to reduced lysosomal degradation. This might be linked to therapy resistance displaying a major problem of targeted cancer therapies in the clinic. This study elucidates the complex regulation of AXL expression.
Cells were cultured in a humidified incubator with 5% CO2 at 37 °C. MDA-MB231 was maintained in DMEM supplemented with 1% sodium pyruvate and 10% FCS. MDA-MB231-D3H2LN (Caliper)  was grown in MEM supplemented with 1% sodium pyruvate, 1% GlutaMAX, 1% nonessential amino acids, and 10% FCS. Hs578T and NCI-H292 (H292) and NCI -1792 (H1792) were cultured in RPMI 1640 medium with 1% GlutaMAX and 10% FCS. Cell culture media and supplements were purchased from Gibco (Thermo Fisher Scientific, Darmstadt, Germany).
Three-dimensional (3D) spheroid culture and cell viability
Matrigel basement membrane matrix (BD Biosciences—Corning, No. 354234; Kaiserslautern, Germany) was diluted to a concentration of 3 mg·mL− 1 in cell line-corresponding serum-free medium. 7000 cells were seeded on top of the solid Matrigel in each well (96-well plate). Viability of cells was determined by ATP quantification using CellTiter-Glo Luminescent Cell Viability Assay (Promega, Mannheim, Germany). The luminescence signal was measured by Clariostar multimode microplate reader (BMG Labtech, Ortenberg, Germany).
Tyrosine kinase inhibitors and cell treatment
BMS777607 was purchased from ShangHai Biochempartner Co., Limited, Wuhan, China (Cas No.:1196681–44-3) with a purity > 98%. Chloroquine Phosphate (CQ, No.S4157 in H2O 10 mg/ml) and DAPT were purchased from Seleckchem (No. S2215, BIOZOL GmbH, Eching, Germany). BB94/batimastat (BB94, No. 2961) and human recombinant GAS6 (#885-GSB-050) were purchased from R&D Systems GmbH. Cycloheximide (No. C1988) was purchased from Sigma Aldrich. All inhibitors were dissolved in DMSO (Sigma Aldrich, Taufkirchen, Germany), except CQ, and stored at room temperature in 10 mM stock solutions.
Reverse transcription-quantitative PCR (RT-qPCR)
Gene expression was analyzed following the isolation of total RNA using the RNeasy minikit (Qiagen, Hilden, Germany) and cDNA using random hexamers and Verso cDNA synthesis kit (Thermo Fisher Scientific, Darmstadt, Germany) according to the manufacturer’s instructions. RT-qPCR was performed with DyNAmo ColorFlash SYBR green qPCR kit (Thermo Fisher Scientific, Darmstadt, Germany) using a LightCycler 480 II (Roche, Mannheim, Germany). Relative gene expression levels were calculated according to the 1.9 -Δ(CT(housekeeping)-CT(gene of interest). Primer sequences: ALAS1, forward: 5′-CTGCAAAGATCTGACCCCTC-3′, reverse: 5′-CCTCATCCACGAAGGTGATT-3′, Human GAPDH, forward: 5′-ACCCAGAAGACTGTGGATGG-3′, reverse: 5′-TTCTAGACGGCAGGTCAGGT-3′, AXL P3. forward: 5′-GAGGGAGAGTTTGGAGCTGT-3′, reverse: 5′-TCATGACGTTGGGATGGTCA-3′, AXL PB, forward: 5′-CAGCTTCGGCTAGGCAG-3′, reverse: 5′-TCCGCGTAGCACTAATGTTCT-3′.
Western blot analysis
Standard mini gel electrophoresis and blotting system was used (Bio-Rad Laboratories GmbH, München, Germany). Proteins were transferred to PVDF membranes and incubated overnight at 4 °C with the primary antibody. Anti- HA-Tag (No.3724), GAPDH (No.5174), AXL (No.8661) were purchased from Cell Signalling Technonoly (New England Biolabs GmbH, Frankfurt am Main, Germany), and AXL H-3 (No.sc-166,269) from Santa Cruz Biotechnology as well as β-ACTIN from Sigma. Species corresponding fluorophore-labeled secondary antibodies (Li-Cor, Lincoln, NE) were incubated for 1 h at room temperature. The fluorescence signals were detected with an Odyssey CLx system and quantified by Image Studio software (Li-Cor). All bands were normalized as described to ACTIN or GAPDH as loading control.
Immunoprecipitation was performed as previously described . The FK-2 antibody (No. BML-PW8810–0100, Enzo Life Sciences GmbH, Lörrach, Germany) was used for ubiquitin precipitation in the concentration of 1 μg per 750 μg lysate. Subsequently, the AXL antibody (No.8661, Cell Signaling, New England Biolabs GmbH, Frankfurt am Main, Germany) was used for western blot analysis.
Cells were detached with Accutase (No. A1110501, Thermo Fisher Scientific, Darmstadt, Germany). Centrifugation was performed at 300 g for 3 min. Cells were fixed with 3.7% PFA at 37 °C for 10 min and permeabilized with − 20 °C methanol for 5 min. Primary antibody Ab 154 (MAB154, R&D Systems GmbH) or Ab 259/2 homemade antibody (clone 259/2, IgG1 isotype) was incubated for 1 h and subsequently incubated for 30 min at 37 °C with Alexa Fluor 488-conjugated secondary antibody (Jackson ImmunoResearch Europe Ltd., Cambridgeshire, UK). Fluorescence intensity was measured using a BD Acccuri Flow Cytometer (BD, Heidelberg, Germany).
SOMA (single oligonucleotide mutagenesis and cloning approach)
Plasmid for AXL wildtype overexpression with HA-Tag was purchased at Sino Biological (Cat: HG10279-CY). Primer for K567R mutation (GTGGCCCTGGGGAGGACTCTGGGAGAG). SOMA was performed according to Pfirrmann et al. with the following modifications: Q5-polymerase was used in combination with standard PCR protocol [30 cycles 1 min per kb elongation]. DNA was isolated using Qiagen PCR purification kit (Qiagen, Hilden, Germany) . DH5α competent E. coli were used for plasmid amplification.
Statistical data analysis
Mean values and SEM are shown. The statistical analysis was performed by the application of an two-way ANOVA in combination with Bonferroni multiple comparison post-test using GraphPad prism 7 (GraphPad Software, Inc., La Jolla, CA, USA). Differences with *P < 0.05 were considered as statistically significant.
Increased AXL protein level after 24 h of low μM treatment with selective AXL TKI BMS777607
Increased viability of tumor spheroids upon low μM treatment with BMS777607
We performed ATP measurements after 72 h of treatment with increasing concentrations of BMS (0.197 μM up to 12.5 μM), to evaluate the impact of increased AXL protein levels on cell viability of 3D-spheroids. Hs578T, MDA-MB231, Caliper, H1792 and H292 were used for spheroid formation and subsequent ATP measurement. Three different cell viability phenotypes were observed. Hs578T cells displayed a concentration-dependent decrease of cell viability. In contrast, H1792 cells showed a concentration-dependent increase of cell viability. The third phenotype was observed in MDA-MB231, Caliper and H292 cell lines, where BMS concentrations higher than 5 μM caused reduced cell viability, whereas concentrations lower than 1 μM led to increased cell viability compared to DMSO- controls, as shown in Fig. 1d. The elevated AXL protein levels correlated with increased cell viability in MDA-MB231, Caliper, H1792 and H292 cell line which might indicate that AXL protein upregulation is part of AXL TKI resistance or feedback mechanism.
Transcription of AXL mRNA was not affected by low μM treatment with BMS777607
The major mechanism that increases protein concentrations is the transcription of coding mRNA. Therefore, we evaluated the transcription of AXL mRNA in Hs578T, H292 and H1792 cells by RT-qPCR after 0.25, 0.5, 1, 2 and 4 h of treatment with 0.5 μM BMS compared to DMSO control. We observed no significant changes of mRNA levels within 4 h of treatment with BMS (Fig. 1e-g), although a 1.3-fold increase of AXL protein levels was evident already after 3 hours of BMS treatment in H292 cells (Fig. 3e). Based on these results we conclude that low μM BMS treatment does not influence AXL mRNA level. AXL mRNA quantity did not change after 24 h as well (data not shown).
The significant increase of AXL protein levels by 0.5 μM BMS777607 treatment is depending on culture conditions
GAS6 mRNA levels were significantly different in Hs578T, H292 and H1792 cell lines. H1792 cells showed significant induction by serum deprivation
GAS6-dependent degradation of AXL was prevented by BMS777607 treatment
BMS777607 impaired GAS6-dependent internalization of AXL leading to cell surface accumulation of AXL protein
BMS777607 prevented ubiquitination of AXL after GAS6 stimulation
K567R gate keeper mutation prohibited the phosphorylation-dependent ubiquitination and subsequent internalization of AXL
BMS is an efficient AXL TKI, prohibiting AXL kinase phosphorylation [23, 25]. Finally, we investigated, if ubiquitin-dependent AXL internalization and subsequent lysosomal degradation depends on AXL kinase activity. Therefore, we introduced HA-tagged AXL gatekeeper mutants into Hs578T (Fig. 6c) and H292 cells (Fig. 6d). The K567R gate keeper mutation prohibits the binding of ATP to the hinge region of the kinase domain, which completely abolished the AXL phosphorylation. Analogous to previous experiments we analyzed the effect of 0.5 μM BMS on AXL abundance after 24 h of treatment . The fully glycosylated 140 kDa AXL is localized at the cell surface and thereby accessible to GAS6. Consequently, only this 140 kDa AXL protein can be protected from GAS6-dependent degradation by BMS (Fig. 6e). We used the 120 kDa AXL protein as a normalization control for transfection efficacy in Hs587T and H292 cells (Fig. 6c-d). We observed that BMS increased the fully glycosylated 140 kDa AXL protein abundance in wildtype AXL transfected cells in similar fashion as the K567R gate keeper mutation. BMS treatment displayed no additional impact on the 140/120 kDa ratio in K567R gate keeper mutants. Consequently, we assume that AXL kinase activity and subsequent RTK phosphorylation is necessary for ligand-dependent receptor internalization and degradation. Blocking of kinase function by BMS resulted in phosphorylation prohibition, impaired internalization and subsequent cell surface accumulation, as observed in Fig. 1a-c. By using a plasmid based overexpression system without 3’and 5’UTR regions, we additionally excluded the impact of BMS on posttranscriptional regulation by miRNAs potentially binding to AXL mRNA untranslated regions.
In summary, we postulate that phosphorylation of AXL is a prerequisite of ubiquitin-dependent internalization and lysosomal degradation, which is completely abolished by BMS. The inhibition of AXL phosphorylation subsequently prevents ubiquitination and results in the accumulation of cell surface AXL via impaired internalization after GAS6 binding.
Our study identified elevated AXL cell surface expression after 24 h of BMS777607 AXL TKI treatment. The complex AXL RTK biology requires a better understanding of the underling mechanism for successful implementation of AXL targeting therapeutics, as therapy resistance still remains the major problem for targeted therapies. Therefore, we focused on mechanisms, by which AXL protein quantity is regulated, starting with transcriptional regulation [28, 29]. AXL expression is controlled by DNA methylation, histone acetylation and transcription factors, including SP1, AP-1 and HIFα, as reviewed by Gay et al. . We excluded the impact of these transcriptional regulators on AXL protein abundance caused by BMS treatment as this would necessarily be caused by increased mRNA levels which could not be observed in our study (Fig. 1e-g). AXL expression is further regulated by post-transcriptional modifications. In dendritic cells, AXL expression is abundant, and in bone marrow-derived macrophages, AXL expression is minimal; however, there is essentially no difference in AXL mRNA copy number in these cells, suggesting a significant role for post-transcriptional or post-translational regulatory mechanisms of AXL expression . Other studies have identified target sequences for microRNA (miRs) including miR-34 and miR-199a/b in the AXL 3′ untranslated region, with correlative findings confirming the effects of miRs on AXL expression [31, 32]. In our study we show that low μM BMS treatment does not influence AXL mRNA level. This was interesting, as we observed a minor increase of AXL protein levels already after 3 hours of BMS treatment in H292 cells (Fig. 3e-f). Using a plasmid based overexpression system without 3′ and 5′ UTR regions we exclude the impact of BMS on posttranscriptional regulation by miRNAs, potentially binding to AXL untranslated mRNA regions (Fig. 6c-d). Alternative splicing events have not been analyzed in this study, although three different splicing variants were described for the axl gene . We haven’t observed a dramatic shift in AXL protein in western blot analysis after BMS treatment, but we cannot exclude a splice variant shift on mRNA level. Translational regulation of oncogenes play an important role in carcinogenesis . Emerging evidence indicates that AXL expression may also be regulated at the translational level. A critical protein for translation initiation is eIF4E, which binds to the 5′ m7G cap of mRNA molecules and thus facilitates ribosomal recruitment . In preliminary experiments we saw a slight, but significant, increase of eIF4B S422 phosphorylation in MDA-MB231 cells and increased ribosome-bound nascent chain puromycinylation in Hs578T and H292 cells after 24 h of low μM BMS treatment (data not shown). In contrast to that result we failed to validate a significant impact on translation by polysome-fractionation and subsequent RT-qPCR of bound AXL mRNA. Therefore, we cannot draw a clear picture, whether the translational machinery is significantly affected by BMS treatment leading to enhanced AXL protein enrichment. To become a functionally mature protein, important posttranscriptional modifications, including glycosylation and signal peptide cleavage, need to occur. Another type of AXL cleavage is commonly referred to as ‘ectodomain shedding’, in which the extracellular domain is cleaved from the cell membrane through actions of various matrix metalloproteinases and A Disintegrin and Metalloproteinase Domain (ADAM) family members, e.g. ADAM10 and ADAM17 . We analyzed the impact of α-secretases and γ-secretases by combinatorial treatments of BMS or BB94 together with DAPT. BB94 blocks α-secretase activity and DAPT is a known inhibitor of γ –secretases. When taking reduction of receptor ectodomain shedding as a potential mechanism for 140 kDa AXL cell surface accumulation, then α-secretases have to be inhibited. Blocking of γ-secretases by DAPT treatment leads to the stabilization of the 55 kDa C-terminal fragment of AXL and causes no accumulation of the 140 kDa AXL protein. We could not prove an impact of BMS on the activity of α- secretases as shown in Fig. 4. Glycosylation is essential for maturation and function of membrane proteins regulating their routing, conformation and ligand binding. For example, inhibition of glycosylation sensitizes cancer cells that are resistant to EGFR targeted therapy to radiation. Tunicamycin inhibits N-acetylglucosamine (GlcNAc) transferase, which catalyzes the first step of protein N-glycosylation in the endoplasmic reticulum. Krishnamoorthy et al., 2013 could show that tunicamycin treatment of CAL62 cells led to AXL protein accumulation as a 100 Da protein in western blot, representing the core polypeptide, whereas the 140 and 120 kDa bands disappeared, indicating that both were N-glycosylated isoforms of AXL . We have not focused on this aspect of posttranslational modification in the present study, but it is unlikely that glycosylation is impaired by BMS treatment as we could even observe an increase of the fully glycosylated 140 kD. Only exogenous over-expression of Ha-tagged-AXL showed the appearance of a potential non-glycosylated AXL protein at 110 kDa in western blot. Neither the 110 kDa band nor the 120 kDa band was significantly regulated by BMS treatment in contrast to the fully glycosylated 140 kDa band (Fig. 6e). This glycosylation of the endogenous or exogenous 140 kDa AXL protein is necessary for ligand accessibility and subsequent full activation of the kinase function . Like for other RTKs, phosphorylation plays an essential role governing the activity and the fate of AXL. Upon GAS6 binding, AXL undergoes dimerization and Y698, Y702 and Y703 phosphorylation. Subsequently, three adjacent residues (Y779 and 821 and Y866) are phosphorylated, representing active docking sites for signal transduction. ATP binding is prohibited by a K567R gate keeper mutation resulting in an inactive kinase domain with loss of binding capability to adaptor proteins, like PI3K subunit p85 [16, 36]. Upon GAS6 binding AXL is activated, internalized and sorted to endosomes through endocytosis, which is clathrin- and dynamin-dependent. From endosomes, AXL can either be transported to the plasma membrane or delivered to lysosomes for degradation [37, 38]. We used chloroquine as a lysosomotropic agent that prevents endosomal acidification leading to inhibition of lysosomal enzymes. We could not show an additional impact by inhibition of lysosomal degradation with chloroquine on the abundance of AXL after BMS treatment (Fig. 4). AXL is also subject to ubiquitin-mediated proteasomal degradation. AXL degradation by proteasomes has been well demonstrated by Paolino et al.. Castias B-lineage lymphoma (CBL) is an E3 ubiquitin ligase, responsible for TAM family ubiquitination and degradation . We could show in preliminary experiments that inhibition of the proteasom by MG132 does not lead to an accumulation of the 140 kDa AXL protein (data not shown). Phosphorylation of AXL tyrosine residues creates a docking site for recruiting CBL . Alternatively, CBL may be recruited to AXL through its interaction with the adaptor protein GRB2 as shown for MET . GRB2 is also implicated in the clathrin-mediated endocytosis of activated EGFR  and Pao-Chun et al. showed that GRB2 is binding to AXL after GAS6 ligand stimulation . A similar GRB2/CBL-dependent internalization mechanism may exist for AXL as well, taking into account that Y821 is an essential tyrosine for binding of GRB2 . AXL small molecule inhibitors prohibit receptor phosphorylation and prevent the binding of adaptor proteins. Among these, CBL leads to receptor downregulation by ubiquitination and successive degradation in the lysosomes. The activation-dependent downregulation is important for keeping a steady-state between active and non-active AXL modes. Here we demonstrated that kinase inhibition hinders the AXL activation-dependent downregulation. As a consequence, the AXL accumulates on the cell surface, where it potentially could be stimulated, once the administration of the inhibitor is stopped. Based on our data, we propose that AXL TKIs inhibit the phosphorylation on the CBL binding site, disrupting the interaction between AXL and CBL and thus restricting ubiquitination of AXL, which subsequently cannot be internalized and degraded in the lysosomes. Proper RTK downregulation is a crucial step of activity regulation, and if not tightly controlled, may cause oncogenic events. ATP binding of AXL is prohibited by a K567R gate keeper mutation resulting in an inactive kinase domain and shows analogous, but not additional effects like BMS treatment on AXL abundance (Fig. 6c-e). Here we report that impairment of downregulation takes place upon inhibiting the activity of AXL by TKIs. Although in the current case the receptor accumulates initially in an inactive state, enhanced phosphorylation of AXL might take place as well within 24–36 h, as shown for BMS by Baumann et al. and for R428 by Chen et al. [38, 42]. This might be relevant in vivo, where concentration gradients of drugs are common in tumors. Our findings could possibly translate into appalling consequences once the inhibitor drops below the inhibitory concentration in some cells within the tumor mass. To our knowledge, this is the first report to describe that targeting of the AXL by small molecule inhibitors leads to its cell surface accumulation by potential interference with a downregulation-associated mechanism. This phenomenon might represent clinically relevant aspect to be considered when following AXL inhibition in clinical setups. Additionally, the release of the soluble 85 kDa N-terminal fragment (sAXL) might be used as biomarker and campaign diagnostic tool as shown for early hepatocellular carcinoma (HCC) and malignant peripheral nerve sheath tumors (MPNST) [20, 21]. We demonstrated that the 55 kDa C-terminal fragment, which is generated as the sAXL is shedded by ADAM10 and 17, was accumulating after BMS treatment in Hs578T (Fig. 4). Consequently, sAXL might be increased in serum of AXL TKI treated patents . Beside kinase inhibition with TKIs or decoy receptors also receptor downregulation is a common mode of action for AXL targeting therapies. This was shown for antagonistic monoclonal antibody targeting AXL , 17-Allylamino-17-demethoxygeldanamycin  and yuanhuadine . As a linkage of kinase inhibition and receptor degradation, proteolysis targeting chimera (PROTAC) technology could be used as a powerful tool for AXL targeting therapy. Burselm et al. could demonstrate that PROTACs are capable of inducing the degradation of active EGFR, HER2, and c-Met. In most cases, PROTACs capable of degradation inhibit downstream signaling and cell proliferation at lower concentrations than similar TKIs without linked degradation machinery recruiting unit. Furthermore, degradation provides a more sustained reduction in signaling, as evidenced by the reduction in kinome rewiring, as observed previously with EGFR, HER2, and c-Met inhibitors, as well as the sustained duration of response even after washout . Based on our study, we would suggest a PROTAC-based strategy for AXL inhibition to achieve a sustained inhibition and depletion of AXL. This might enhance the efficacy of targeted AXL therapies in the clinics.
AXL tyrosine kinase inhibitors (TKIs) are currently under clinical evaluation. We observed by Western blot and flow cytometry analysis that AXL TKI BMS increases AXL protein levels after 24 h of treatment. We demonstrate that AXL kinase activity and subsequent RTK phosphorylation is necessary for GAS6-dependent receptor internalization and degradation. Blocking of kinase function by BMS results in phosphorylation prohibition, impaired internalization and subsequent cell surface accumulation. Our data suggest careful consideration of anti-AXL clinical protocols because feedback loops and resistance formation might countervail targeted AXL therapy. An alternative strategy to circumvent feedback loops for AXL targeting therapies may exist in linkage of AXL TKIs to a degradation machinery recruiting unit (PROTACs). This might result in a sustained inhibition and depletion of the AXL from tumor cell surface and enhance the efficacy of targeted anti-AXL therapies in the clinics.
We thank Dres. Singh, AK., Neuhaus, H. and Holstein, I. for critical reading of the manuscript.
This study was designed by T.R. W.A and L.M performed the experiments; T.R and L.M analyzed and interpreted the data; T.R and L.M wrote the manuscript. All authors read and approved the final manuscript.
HaPKoM, University Halle-Wittenberg, Halle (Saale), Germany.
Ethics approval and consent to participate
Consent for publication
The authors declare that they have no competing interests.
- 15.Lew ED, Oh J, Burrola PG, Lax I, Zagorska A, Traves PG, Schlessinger J, Lemke G. Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities. Elife. 2014;3. https://doi.org/10.7554/eLife.03385.
- 36.Fridell YW, Jin Y, Quilliam LA, Burchert A, McCloskey P, Spizz G, Varnum B, Der C, Liu ET. Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase. Mol Cell Biol. 1996;16:135–45.CrossRefGoogle Scholar
- 37.Goyette MA, Duhamel S, Aubert L, Pelletier A, Savage P, Thibault MP, Johnson RM, Carmeliet P, Basik M, Gaboury L, et al. The receptor tyrosine kinase AXL is required at multiple steps of the metastatic Cascade during HER2-positive breast Cancer progression. Cell Rep. 2018;23:1476–90.CrossRefGoogle Scholar
- 43.Leconet W, Chentouf M, du Manoir S, Chevalier C, Sirvent A, Ait-Arsa I, Busson M, Jarlier M, Radosevic-Robin N, Theillet C, et al. Therapeutic activity of anti-AXL antibody against triple-negative breast Cancer patient-derived xenografts and metastasis. Clin Cancer Res. 2017;23:2806–16.CrossRefGoogle Scholar
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

domain: biology


Welcome to the website for the Village of Algonquin!
Applications will be included with posted vacancies and must be received by 5:00 p.m. CST on the closing date of the job posting. If you are applying for a current Police Officer recruitment, please ensure you complete the Police Officer Application. All other applications WILL NOT be accepted.
If you are interested in working for the Village and a position is not currently available, please complete the Employment Interest Card with your information. If a position becomes available within six months of submitting the Interest Card, a recruitment notice and employment application will be sent directly to you.
PLEASE NOTE: If you have submitted your information to be included in our next Police Officer recruitment process, it will remain on file until the next process has been scheduled.
New positions are typically added to departmental budgets effective May 1st of each year, with vacancies occasionally arising at other times.


text:
NORFOLK, Va. (WVEC) --All those hours you spend looking down at your smartphone really can start to take a toll on your body.
Health experts are warning people about “text neck,” saying smartphones may be responsible for pain and damage to people's necks and spines.
"When I look at my phone for a long time, the back of my neck will hurt for a bit if I'm looking down," college student Hunter Crumpler said.
Spinal surgeon Kenneth Hansraj found that bending the neck forward and down increases the weight on the cervical spine. His research showed that bending your neck at a 60-degree angle is like draping a 60-pound weight around your neck.
"That's hard to believe. Sixty pounds of weight just from looking down? I don't know, you got to show me a little proof on that one," student Gary Banks said.
Well, the proof is in science.
Virginia Beach chiropractor Dr. Tina DeGiorgio says it's not necessarily the weight that changes-- it's the center of gravity that changes, making it seem like it's heavier.
"When your head moves forward, it changes the center of gravity, therefore increasing the amount of pressure that's put on your spine," she said.
"You got to keep rolling your shoulders, and that doesn't do anything after awhile," college student Shelby Johnson said.
But it's not just the pain you should be worried about.
Dr. DeGiorgio says text neck doesn’t just make you sore. It can cause you to be more injury prone and permanently damage your spine, making you weaker, slower, less efficient and depressed.
"Your body starts producing different hormones that create -- could be fear, low self-esteem-- all the things-- characteristics you would see for somebody who walks like this. Low self-esteem is actually a big issue with people who do this too because they're not looking up, they're not looking around and having that confidence," she said.
Dr. DeGiorgio says the problem is growing, and her patients are getting younger and younger.
“You’re having 16, 17-year-old kids with the spine of a 70-year-old because of the degeneration and the constant pull on the spine. You do the most damage from late teenage to late 20's because after you're 20, 30, 40-years-old, you're just an accumulation of what you've done to yourself,” she explained.
The earlier you start taking steps to prevent text neck and treat it, the better.
Dr. Degiorgio recommends yoga, stretching, mobility exercises and epsom salt baths, which contain magnesium. Consult with a chiropractor about massage therapy and getting adjustments to your spine, and most importantly, just be aware.

domain: health


text:
Become a Pharmacy Insider
Subscribe to our newsletter for promotions, health news and savings
Your One Stop Shop
Avoid medication non-adherence and let our pharmacists help you better manage your medications.
We offer express local delivery and shipping at no cost to you.
Our pharmacists work with you to coordinate benefits and find financial assistance.
Your Pharmacy Experts
Trust Us With Your Health
Read Our Patient Reviews
"Best pharmacy in town! Everyone here is very helpful and caring. I always recommend them friends and family."
"They go out of their way to find lost prescriptions! Thank you!"
"Always professional and courteous but most of all true personal attention and customer service."
Catchings Prescriptions combines high quality products with personalized care. Our staff is happy to help you with any questions you may have.
Check out our weekly health news blog, or subscribe to our newsletter and receive updates on health articles, promotions, specials and much more.
We offer a wide variety of services including conventional prescription filling, long term care, immunizations and much more.
We'd Love To Hear From You
At Catchings Prescriptions, we’re committed to helping you live a healthier life. Our pharmacy staff would be happy to help you with any questions you may have.
- SEND AN EMAIL
- Phone: 806-355-2924
- Fax: 806-355-1029

domain: medical


Check out the latest news on Construction Projects, Bond Projects, Streets, Sidewalks, Project 180 and more in Oklahoma City.
Registered Oklahoma City voters who want an absentee ballot to vote in the Better Streets, Safer City special election on Sept. 12 must request the ballot by Sept. 6.
08/30/2017 8:55 AM
Beginning on Wednesday, Pennsylvania Avenue will be temporarily closed between NW 178th and NW 192nd streets for widening and drainage improvements.
08/21/2017 8:55 AM
For those not already registered, eligible Oklahoma City residents have until Aug. 18 to register to vote on the Better Streets, Safer City special election on Sept. 12.
08/08/2017 8:45 AM
Oklahoma City residents are more satisfied with their community than most Americans who live in big cities.
07/18/2017 1:29 PM
Skaters and other interested Oklahoma City residents are invited to get information and provide feedback on the Stars & Stripes Skate Park Project at a public workshop this month.
07/11/2017 8:53 AM
A summary of special events and construction projects that will affect traffic in the downtown Oklahoma City area from June 30-July 6.
06/30/2017 3:34 PM
Mayor Mick Cornett and other Oklahoma City leaders broke ground Thursday on the transformative MAPS 3 Park, revealing Scissortail Park as the name residents chose in a public online vote.
06/29/2017 10:45 AM
The Oklahoma City Council voted to call a special election Sept. 12 for voters to consider investing more than $1.2 billion in critical infrastructure like streets and sidewalks, including an annual $26 million boost for public safety and other day-to-day operations.
06/20/2017 3:34 PM
Sept. 12 special election set for bond and sales tax proposals, amendments to dog ordinances, special events, food donation for homeless pets, sales tax and more.
06/20/2017 12:31 PM
The Oklahoma City Council has scheduled a public hearing Tuesday regarding a proposed amendment to the temporary sales tax initiative introduced for consideration last month.
06/16/2017 3:23 PM
FY 2018 budget approved, bond and sales tax initiative public hearings and a proposed update to ordinances related to dogs.
06/14/2017 2:12 PM
The Oklahoma City Council is scheduled to vote next week on sales tax and bond package proposals that would invest more than $1.1 billion in funding for streets, police, firefighters and other basic needs, and an annual injection of $26 million for day-to-day operations.
06/13/2017 1:08 PM
Proposed FY 2018 budgets from Utilities, Parks & Recreation and Airports.
06/06/2017 11:49 AM
More than 5,000 MAPS 3 Park name ideas have been narrowed to six, and you can help pick the winner with an online vote.
06/01/2017 5:46 AM
2017 bond election and sales tax initiative proposals, MAPS 3 Park update, special events, sales tax revenue, Zoo admission prices and more.
05/31/2017 9:28 AM
More than $1.1 billion in funding for streets, police, firefighters and other basic needs and an annual injection of $26 million for day-to-day operations are included in sales tax and bond proposals under consideration by the Oklahoma City Council.
05/30/2017 12:44 PM
A summary of special events and construction projects that will affect traffic in the downtown Oklahoma City area from May 19-26.
05/19/2017 3:01 PM
Special events, bond projects and more.
05/16/2017 11:12 AM
Overview of the proposed FY 2018 budget and presentations from Public Works, Public Transportation and Parking, and Development Services.
05/09/2017 9:35 AM
Updates on next year's budget, special events, the MAPS 3 Will Rogers Trail and more.
05/02/2017 11:29 AM


text:
Excellent Reviews Ouix 4V Leather Stool Red by Abbyson Living
Shopping Ouix 4V Leather Stool Red On the internet Evaluations
Number of Selections When you purchase furniture online there's a great variety of the provided items. It happens so often that a kind of furniture which you may not even have considered while planning attracts your eye, and you think it is as a better option to have it in your home than the 1 you were hoping to find. Easy Comparison If you have an excellent variety of items as stated before, then you certainly will have a need to compare various furnishings on offer. Having the considerations on one display retains it easy for that website consumer to select an item of furnishings. Easy accessibility All you need to do is select how big furniture and merely order the main one you like and the Ouix 4V Leather Stool Red supplier does the rest of the work. Buying furnishings on the internet is a straightforward choice. You have access to the websites from your living spaces whilst waiting for your favorite sport to begin, and after the game, you will have put your desired furnishings inside your cart. It saves you from lengthy journeys to your local furnishings provider. Provides and discount rates Lets face it, your good old nearby Ouix 4V Leather Stool Red provider might be a celebrity merchant in your locality, but his company is not as wide being an online shop. Since the online stores deal with loads of clients, they are able to provide better discount rates while offering around the Ouix 4V Leather Stool Red they provide. Easy results Not that you'll require it every time, but most of the online retailers possess a substitute or return policy which lets you come back or replace the item if you dont find it correct. That is among the best features of buying furniture on the internet. So, you can just return or substitute a bit of furnishings on the internet, if it's damaged or if it does not match your room properly. Referring to furnishings not coordinating your room, some online retailers, like City Ladder, etc. supply in-house discussion which can be very helpful. Should you prefer a faster help make extra space in your space then you need to follow some suggestions for making the most of space inside a room.
How to Pick Ouix 4V Leather Stool Red Home Furniture
You lately bought a new house and you discovered your self asking, "Ok now what?" selecting a house is a thing, selecting household furniture is another. Ouix 4V Leather Stool Red the core function of a home. It should be comfy yet suits your personal flavor. Below are great tips regarding how to select household furniture. Look through house dcor magazines or surf the net for inside creating web sites. Also, observe other's house. You will get several kinds of ideas that you can choose from. Consider the dimension, design, and also the general style of your property. Furthermore, consider what sort of way of life you've and also consider your day-to-day existence. You should consider stuff that individuals within your house or visitors will more likely use very often. This can help you choose furniture particulars such as what color and type of fabric to make use of. Figure out your house's color scheme. Your walls is the background for everything. You may also make large Ouix 4V Leather Stool Red like a foundation color and accessories such as throw pillows and other decorations as highlight colors that will add spice for your room. Research on different styles and prices of furniture. You can go to display rooms and furniture stores and you can also go to websites. Not solve these questions . begin to see the most popular house furnishing in today's interior design design but also you can get suggestions from various topics associated with home enhancements. You ought to be prepared when you go to Ouix 4V Leather Stool Red store. You should provide the types of materials you have in your house for example drapes, table top, area rugs, carpets and rugs, etc. moreover, provide dimensions along with you so that you will not make a mistake when choosing furniture.
Tips to Buy Ouix 4V Leather Stool Red Home Furniture
Understanding where to begin when it's time to shop for furniture happens to be an overwhelming job for just about anyone. It is often an enormous buy, and not to be taken lightly. You have to consider a great deal of elements, including your room, colour scheme, fabric, Ouix 4V Leather Stool Red size, relieve, and excellent. The very first issue to consider with household furniture is when considerably place presently obtainable. If the furnishings are also large, you may make your neighborhood really feel also little, and the other way around. So the size in the Ouix 4V Leather Stool Red you wish to purchase as well as the dimension with the place create a huge impact on your options. You must know the way a great deal your price range is perfect for the new household furniture. The reason for this really is that you need to purchase the finest good quality Ouix 4V Leather Stool Red feasible in your price range, but you won't want to go overboard and go into financial debt if you get your new items. You'll be able to use the on the internet to search out what styles of furnishings you want and also to have ideas. You'll be able to even order your furnishings on the internet if you want to, although it really is suggested that should you ever find furnishings you want on-line, visit a nearby shop first to become positive you like the way it looks and feels in person. A single good problem about this really is which you can view it inside a display room amongst matching items and complimentary decorations.

domain: design


(Carrollton, Georgia—May 16, 2017) The Carroll County School System celebrated its 2017 Valedictorians and Salutatorians at a special recognition breakfast on May 16, 2017 at Sunset Hills Country Club.
Loy Howard, President and CEO of Tanner Health System, was the keynote speaker. Dr. Jon Anderson, Board Chairman, offered a moment of reflection and inspiration. Each student was presented with a plaque for their achievement by Scott K. Cowart, Superintendent and Dr. Anderson.
The event was sponsored by Southwire, West Georgia Technical College and the University of West Georgia.


DIYAREA Goat Milking Machine, 2 in 1 Milk Machine for Cows & Goats, Electric Vacuum Pump Milker Machine with Adjustable Suction, 7L Stainless Steel Bucket. [Continuously Adjustable Suction] - Unlike traditional pump, our vacuum pump features function of adjustable suction. You choose the proper suction by adjusting the knob according to your needs. As a result, it prevents injury to your goats, because different goats need different suction.
[Healthy Materials] - The milk bucket is made of food grade 304 stainless steel. The milk suction head is food grade silicone, which is unique designed for cows and goats. Its inner surface is very smooth, which can provide a healthy, soft and comfortable milking environment for animals and protect their breasts safer from insanitation and sickness. [Automatically Stop When Milk is Full] - When the milk reaches the set amount, it will trigger the automatic stop device located on the inside of the lid. At the same time, the sound of the pump will change and it will automatically stop milking to protect the host and avoid milk spills.
[Save Time and Labor] - The milking machine can be assembled in 1 minute, easy to use with the least technical experience, anyone can us. Labor and time are saved due to using a electric milking machine. It also saves your hands from getting sore. [7L Large Capacity] - This electric milking machine is suitable for home use for both goats and cows. The 7L stainless steel bucket is a perfect tool in milking, storing and transporting fresh milk in dairy farm.
Also, it is an wonderful gift for friends. Any product you return must be in the same condition you received it and in the original packaging.
We usually respond within 24 hours on weekdays. Thank you for shopping at our store.This item is in the category "Business & Industrial\Agriculture & Forestry\Livestock Supplies\Dairy Cattle". The seller is "ganuj_91" and is located in this country: US. This item can be shipped to United States.


text:
Misty Cooper's divorce was pending when she met Quentin Ritter at an AA meeting. They shared their love of alcohol and good times. But Misty would never see the finality of her divorce. Follow Mike McCarthy, Montana's number one prosecutor, as he takes us through the murder trial of Misty Cooper. Does Mike have the right defendant on trial? The surprise ending will tell the truth.
About the Author
Barbara Shepherd was a court reporter before retiring in Arizona. She receives her inspiration for her books from the many criminal trials for which she reported in Superior Court. She also worked as a legal secretary for civil attorneys as well as prosecutors. Her love for justice drove her to make the prosecutor her star character. She continues the Mike McCarthy series in her new book, Act of Lust, to be released in the fall of 2016.

domain: library


text:
Asap Rocky is a man of many talents as he is an actor, record producer but we generally know him as a songwriter and a rapper. He came into the limelight when he released his debut mixtape Love A$AP and upon releasing Long Live Asap.
A$AP album which debuted to no.1 on Billboard 200. Today he has established his name in the hip-hop circles and made some pretty good cash as well. So, what is Asap Rocky net worth as of 2022 and how much do you know this rapper? Well hand around and find out more.
Biography & Wiki
Born 1993 Rakim Mayers who goes by his professional name Asap Rocky hails from Manhattan, New York. He is the son of an American/African mum, and his dad hails from Barbados. His education background is not well known though he began his passion for music at the age of 9 and took it more fateful after his father and brother were killed in their notorious neighbourhood.
Asap Rocky Personal Life: Affair, Girlfriend, Married, Wife, Children & Family
Rocky started courting the renowned singer, Iggy Azalea since 2011. Unfortunately, the two broke up in 2012 even after Iggy got a tattoo of her boyfriend’s album name. Currently, it’s rumored that Asap and Kendall Jenner are together.
Rocky began his career in a rap troop, ‘A$AP Mob’ which consisted of many individuals with different professions. He went ahead to launch his single, ‘Purple Swag’ which debuted in 2011 becoming everyone’s favourite. After his success he released other songs like; ‘Peso’ and an album, ‘Live, Love, Asap’ which also did well. Rocky also launched his record studio, Asap Worldwide in collaboration with his colleague called Asap Yams.
His debut mixtape, ‘Long, Live, Asap’ sold over 500,000 pieces in the US and was certified platinum by RIAA. Rocky released his sobering mixtape, ‘Beauty & The Beast: Slowed Down Sessions’ in 2013 which consisted of moody singles. His other successful songs were, ‘LSD’ and ‘Everyday’ which topped the US charts and auctioned over 116,000 in the US and also sold well in other countries. To date, Asap has released two debut albums; Long. Live. Asap (2013) and Long. Last. Asap (2015).
On his acting career he has made his acting debut with the films; Dope 2015, Pop-star: Never Stop Never Stopping 2016, Zoolander 2 2016, and TV series; Animals 2016. As of today, he has built a name for himself as a musician and has collaborated with several notable names in the music industry such As Danny Brown, Juicy J, Lana Del Rey, and Schoolboy Q.
Awards & Achievements
On awards and achievements Asap has received a BBC selection in the category of sounds in the 2012 poll. He has also been nominated in 2 Grammy Awards and many Bet Awards, but he only championed in the NAACP Image Award in the category of best collaboration with Alicia Keys.
Asap Rocky Salary, Net Worth & Earnings
As of August 2022, Asap Rocky net worth is $7.5 million. His net worth figures have been as a result of his music sale and concert tours among his other profession. To add some cash on his wallet Asap Rocky net worth gets a boost from brand endorsements, such as the $3 million contract he signed with Polo Grounds Music, others are RCA Records, in addition, William Morris Endeavor.
Being an entrepreneur, he gains a dollar from his businesses including his merchandise company that deals with fashion clothing which he launched with his designer friend, Raff Simons.
7 Facts You Need To Know About
Though he has the laid-back attitude, he is one of the New York’s most popular Hip Hop artists, and we can’t deny his style of music which is smooth and breezy is among the most attractive you want to listen to. Today he can be named among the big artists of the future if the trend continues but other than his music what else don’t you know about Asap Rocky.
1. Asap Rocky admitted acting is boring and the process isn’t something glamorous though he wants to act even more.
2. The kind of music he loves to listen to it’s the classical music because it makes him feel like a mobster.
3. He still goes to Harlem his old neighborhood to visit his grandmother every Mother’s Day.
4. The reason why he doesn’t Harlem more often because the place lost its vibrancy and makes him depressed. It was a jovial place, but now it’s not.
5. He used to be a big fan of Old Navy, and it influenced his sense of style.
6. He has accepted who he is and he is more comfortable with himself and the best thing he doesn’t feel weird anymore as an artist.
7. On his views regarding the rappers from Atlanta well he acknowledges the most dope hip hop originates from there, but he thinks that all sound the same.
Asap Rocky net worth is just a reflection of how successful he has become over the years and within the industry. In 2019 we know he is cooking something for us and we can’t wait to see what he has for his fans.
Rеаl Nаmе/Full Nаmе: Rakim Mayers
Аgе: 34 Years, Born on 3 October 1988
Неіght: 5′ 10” (178 cm)
Gіrlfrіеnd: Kendall Jenner
Wіfе: Not Married
Nеt Wоrth: $7.5 Million
Ѕоurсе оf Wеаlth: American rapper, songwriter, record producer, and actor

domain: artistic


My goal is to help you move your great idea forward, and I’m thrilled to have the support of some specialized partners who’ve been in your shoes many times before.
Here’s a behind the scenes shot from Which Way There, my commissioned screenplay now in production in Georgia!
The marker with a key to the sacred Scriptures, and what all women need to live their lives.
While it was all remarkable, a lot of you are writers; and as a writer, too, I especially appreciated a couple of places that stood out for their literary history:
I was enjoying a pint by myself in Sandwich last week, and I overheard this:
There’s something oddly involuntary about it, like we’re being driven out rather than driving out with our own feet to the pedal.
I’ve been a total mess lately. One minute I’m mid-air, high on the knowledge we’ll soon bask in sunshine and not have to face the woes of deep seasonal depression. The next minute, I’m saying goodbye to dear friends and realize it’s a REAL goodbye, the kind that lasts a long time, and I’m undone. If there’s anything …
A bittersweet announcement, folks: We’re trading undependable public transport for dependable traffic.


Syence master the art of hybridization on new ‘bass pop’ EP
Via Create Music Group comes bass pop, a five-track project dispensed by Syence, a duo dreamt up by Zach Montoya and Brayden James. Laced with toplines supplied by Kyle Reynolds and Jake Neumar, bass pop bolds wanders through elements of melodic-dubstep, house, and mid-tempo.
The EP—Syence’s answer to their last non-bass pop release, “think about u”—was led by the Reynolds-assisted “truth,” a dramatic pop-guided delivery punctuated by future-bass. Fellow bass pop tracklistings “hate u like you love me” and “talking way too much” make use of catchy vocal harmonics and mid-tempo progressions while the EP’s concluding enclosing two tracks tap more into pop and bass. When asked about the musical influences and personal experiences that colored the creative process behind bass pop, Syence shared,
“bass pop has always been inspired by the things carved out in its name: bass production and pop vocals. We’ve spent years exploring different genres both in our production, our casual listening in our day to day lives, and we’ve always wanted our sound to represent both of us, not just one or the other. As we’ve gotten to know each other and ourselves, we soon realized that combining our joint love for bass and pop would be the best way to express ourselves as a duo and as Syence.”
Synce added that their inspirations today include a range of artists such as Louis the Child, Skrillex, Whethan, Oliver, Haywyre, Zedd, and more. A slew of individual songs have also “helped [Syence] carve out [their] sound like ‘Savage’ by Whethan, MAX, and Flux Pavilion, as well as Oliver’s remix of ‘Electric Love’ by BORNS,” they say.
To date, Syence have amassed more than 21 million plays on February’s “a little bored” with RUUTH on the video social app Triller. The pair recently signed with LA Reid’s label, Hitco Entertainment, joining the likes of Jennifer Lopez, Dixie D’Amelio, SAINt JHN, and Outkast’s Big Boi as well as booking agency, Wasserman Music. Syence will make their premiere festival debut at Insomniac’s Countdown NYE festival this New Year’s 2021. Stream bass pop below.
Featured image: Syence/Facebook


- Bullet Points: Boston Top Cop Evans – Residents Don’t Need To Own Shotguns / RiflesPosted 12 hours ago
- Hired! Office Body LanguagePosted 13 hours ago
- Border Disorder: A Plan From House RepublicansPosted 1 day ago
- AEHQ: FOX Poll: Midterm Election InterestPosted 1 day ago
- Housecall for Health: Fist Bump For HealthPosted 2 days ago
- Obamacare Data Discrepancies Could Jeopardize CoveragePosted 4 weeks ago
AMA Supports Required Obesity Classes For Kids
America’s largest physician organization is stepping up the fight against obesity.
FOX News Radio’s Lilian Woo reports:
The American Medical Association throwing its weight behind new policies to try and fight excess weight. Agreeing to support legislation requiring classes aimed at preventing obesity for grades one through twelve.
The AMA also supporting the idea of taxing sugar sweetened sodas as one way to help pay for the programs. Though the group stopped short of a full fledged endorsement. Some doctors thinking soda taxes would disproportionately hurt the poor.
Obesity affects about a third of U.S. adults and almost one-in-five kids.
Lilian Woo, FOX News Radio.


text:
Albany, NY – Assemblymember Amy Paulin (D-Scarsdale) announced that her bill (A.9169/S.8262) has passed in the New York State Assembly which requires all airports of the Port Authority of New York and New Jersey, which are JFK International, Newark Liberty International, LaGuardia, New York Stewart, and Teterboro airports, to provide information on support services for human trafficking victims. It will now proceed to the New York State Senate where it is sponsored by Senator Anna Kaplan.
The bill requires the airports to have informational cards or signs available in public restrooms. Such items would contain information on services for trafficking victims as well as the national human trafficking hotline number.
“Since trafficking networks often rely on air travel to transport victims, we are including airports in our efforts to help these victims,” said Assemblymember Paulin. “For some victims, the information they will see in an airport restroom may be the only opportunity to learn about services available to them. Ideally a victim will take a card or a photo of a sign and call the hotline for help either on the spot or at a later time.”
Human trafficking is a global phenomenon that generates $150 billion in annual profits. In 2021, an estimated 25 million people were trafficked. Airports are known hubs used to traffic victims both internationally and domestically, and as a result they are an ideal location to provide information about victim services. This information will inform victims, as well as other travelers, about the availability of services.
Pursuant to the bill, the posters and cards must include information on human trafficking services and must prominently display the national human trafficking hotline number. Many victims are heavily supervised and controlled while in transit, preventing them from safely seeking help or finding resources for fear of retaliation. By having the victim services informational signs or cards posted in all restrooms, victims will have easy access to the information.
“Through this legislation, airports can assume a more prominent role in responding to and preventing human trafficking,” said Assemblymember Paulin. “It will also afford victims a resource to help escape their capture.”
This bill is the latest in a host of legislation authored and passed by Assemblymember Paulin designed to strengthen New York’s laws against human trafficking. In 2014 she passed a law ensuring that human trafficking victims who are 16 and 17 years old will be treated as victims instead of criminals and get the services they need (Ch. 402 of 2014). In 2015 she passed the landmark “Trafficking Victims Protection and Justice Act” to increase the accountability of buyers and traffickers, providing law enforcement with additional tools to identify traffickers, and providing victims recourse to recover damages from their traffickers (Ch. 368 of 2015). In 2016 she passed a law requiring hospitals to establish written policies and procedures for the identification, assessment, and treatment or referral of suspected human trafficking victims (Ch. 408 of 2016).
In 2018 Assemblymember Paulin passed several anti-trafficking laws, including the End Child Sex Trafficking Act, which eliminated the requirement for proof of force, fraud, or coercion in order to prosecute an individual for the class B violent felony of sex trafficking of a minor (Ch. 189 of 2018). Another law she passed in 2018 requires lodging facilities to provide information about services for human trafficking victims on cards in public areas, including in their public restrooms and guest rooms (Ch. 190 of 2018). She also passed a 2018 law which allows any county to move an action pending in a local criminal court to a human trafficking intervention court (Ch. 191 of 2018).
Anita S. Teekah, Esq., Senior Director, Safe Horizon Anti-Trafficking Program, said "Safe Horizon's Anti-Trafficking Program is grateful to Assemblymember Paulin for her steadfast and unwavering support of victims and survivors of human trafficking. Her recently passed bill will provide valuable and life-saving information to victims in transit during their trafficking and will hopefully connect victims to the services they critically need as they self-empower after escaping trafficking."
Nancy Downing, Executive Director, Covenant House New York, said “Trafficking victims, especially those trafficked from abroad, may find themselves in airports confused and scared with no idea of who to trust. Seeing posted information on how to get help could be their chance at freedom. Awareness of the realities of human trafficking and how to access services needs to be far reaching and we applaud Assemblymember Paulin's efforts to have this information posted in heavily populated New York airports.”
Dorchen A. Leidholdt, Esq., Director, Sanctuary for Families, said “Sanctuary for Families, the largest provider of holistic, dedicated services to gender violence survivors—including human trafficking survivors—in New York State, commends Assemblywoman Amy Paulin for her long-standing leadership in the fight to prevent and combat human trafficking. We applaud her success in securing the support of the New York State Assembly of a bill that requires airports to publicize information on support services for human trafficking victims. Providing this information to victims, and those in a position to assist them, in the very destinations in which they are being transported for purposes of sex and labor trafficking will prevent exploitation and save lives.”
“We must continue to extend protection, services, and assistance to victims, while also strengthening laws which hold those that enslave and exploit children through the commercial sex trade accountable,” said Assemblymember Paulin. “I am grateful to my colleagues in the Assembly for passing this bill and now look to my Senate colleagues to do the same. It’s critical that we help victims escape lives of abuse and exploitation at the hands of their predatory traffickers.”

domain: sociology


text:
Busch Gardens' The Serengeti Plain
is an environment in which the inhabitants are free, roaming within a mock-up of their usual habitat.
On a "safari" ride in the Serengeti Plain
, I saw exotic animals including rhino, wildebeest and ostrich.
On a 'safari' ride in the Serengeti Plain
, I saw exotic animals including rhino, wildebeest and ostrich, and even got to hand-feed a baby giraffe which came up to the truck.
Beginning in December, the Wildebeest herds, numbering about 1.7 million move south, accompanied by approximately 250,000 zebras, traveling through the crater from the Maasai Mara in Kenya, into the Serengeti plain
in Tanzania, then retreat back north in June.
The holiday run by Aviemore firm Wilderness Scotland was featured alongside tours such as trekking across the Serengeti plain
, biking in Transylvania and wolf-watching in Montana.
Bird gardens, cheetah runs, croc and alligator pools, tiger dens, gorilla pens and the Serengeti Plain
- 65 acres of "African" grassland where zebra, giraffe, rhino, antelope and ostriches roam free (or as free as a wild animal can roam in 65 acres!).
The wildebeest come here from the Serengeti Plain
in Tanzania and begin their migration in June, after the rainy season.
The petition follows on an article co-authored by 27 international scientists in the journal Nature that details the potential impact of the highway, including posing a threat to the annual trek of 2 million wildebeest across the Serengeti Plain
As the book shows the beauty of the Serengeti plain
, it also exposes some of the dangers that animals experience daily from poachers and predators.
"Southern Serengeti & The Great Migration" reveals the broad, flat Serengeti Plain
, known for the Maasai people who co-existed in harmony with wild animals for thousands of years.
East Africa's Serengeti plain
has a like reputation.
Edy would see the flamingos of Lake Nakuru, I the wildlife on the Serengeti Plain

domain: geography


The anti-corruption helpline of the Delhi government got off to a roaring start on Thursday, the first days of its operation – 3,904 calls, of which 53 were of serious nature.
Chief minister Arvind Kejriwal said the helpline received a great response within a few hours of its launch.
On Wednesday Delhi government announced the anti-corruption the helpline number- (011) 27357169 to help the common man to lodge complaint corrupt practices in any wing of the state government on the helpline number. On Thursday, Kejriwal said this number will be replaced with a four-digit number to be made public on Friday.
That said, a shortage of attendants to take the calls was felt – only 824 calls could be responded to. To begin with only 10 employees were deployed to attend to the calls but with the inflow of calls too heavy and the number was increased to 15. The number will go up to 30 by Friday.
Out of the 53 complaints of serious nature, 15 complainants refused to conduct a sting as suggested by advisers of of the Anti Corruption Bureau (ACB). Of the remaining 38, stings have already been done in some cases. “People have done quality sting operations. ACB will start laying traps to catch these corrupt official red handed,” Kejriwal said.
He also announced that to address people’s grievances he and his ministers will interact with the public. “Every Saturday my ministers and I will sit outside the Delhi Secretariate from 9am to 11am and listen to public grievances,” he said.
The Delhi government has also proposed to recruit 100 judges to clear the backlog of cases. Delhi Law Minister Somnath Bharti met the chief justice of the Delhi high court and said, “The priority of these judges will be to fast track cases related to women.” Bharti said that the government will introduce the Jan Lokpal Bill by the end of this month. “The new bill will replace the existing Lokayukta Act of Delhi,” he said.
Calls received at anti-corruption helpline of Delhi government 3904
Calls attended by the helpline 824
Complaints of serious nature 53
Every Saturday Chief Minister and his cabinet will sit outside Delhi Secretariate to hear public grievances.
Every day a minister will take listen to public grievances related to his/her ministry.
Delhi government has sent a proposal to recruit 100 Judges
Delhi government has assured to make a schedule of power cuts.


text:
What is the cost of IUI in Amroha?
If you want to determine the IUI cost in Amroha, then you must need to determine the requirement of infertile couple and the complexity of their case. You need to spend as little as Rs. 3000 to Rs.5000 as the average IUI cost in Amroha for a single cycle.
The average IUI cost can be fluctuating as it depends on the number of IUI cycles that you should go through to conceive. When you consider the IUI success rate, it is high as compared to the other fertility treatment. When you are in search of a safe and effective infertility treatment, then intrauterine Insemination is the best and effective treatment. To find out the actual cost of IUI treatment process, you need to see advice of a fertility expert at the reputed fertility center in Amroha. The IUI treatment in Amroha is quite affordable than other cities.
IUI Process Cost in Amroha
Many things you need to consider before go for the IUI treatment. If you are in search of actual fertility treatment cost, then you should consider the age of woman, the number of IUI cycle and the medical history of couples. The IUI treatment cost in Amroha is as low as Rs. 6000 and much more competitive when compared to the other fertility treatments.
Step By Step IUI Procedure
Pre-Testing for IUI
Your fertility doctor will do some major testing before suggesting IUI treatment to couples. There are few tests like ultrasound and blood tests which might help your fertility expert to follow the maturity of the eggs.
Step 1: Stimulate Egg cell Growth:
In order to mature the eggs, this treatment is used.
Step 2: Trigger Shots
A trigger injection is given for the release of the eggs by a nurse at the fertility clinic. After 36 hours of giving this trigger injection, your IUI is proceed.
Step 3: Pregnancy Test:
Some Test are advised to confirm the Pregnancy
Ready to get started? Please contact us today and we’ll be happy to provide a free, no obligation quote.
When is IUI Treatment Recommended?
Those women who are suffering from endometriosis, or have unexplained medical conditional, this treatment is better.
How Does IUI Treatment Help Fertility?
This treatment helps the couple to increase the chances of pregnancy and to complete the family. This treatment is effective as compared to other fertility treatments.
What are the costs of IUI cycles in Amroha?
Natural Cycle IUI Treatment Cost
In this cycle, the semen is purified and injected closer to the fallopian tubes in order to increase the chances of pregnancy. The treatment also includes the charge of removing the sluggish semen and collecting the high-quality sperms for the treatment.
Clomid or Letrozole with IUI Cost
In this IUI process, you will be advised for a blood test and an ultrasound which confirms the pregnancy. In order to increase the chances of pregnancy, oral drugs will be prescribed by your fertility experts. This will further raise your IUI cost with up to Rs. 2000.
Dr Pranay Shah
Director and Chief Fertility Consultant
Dr. Divyesh Bhalodia
Counseller and Communicator
Dr. Dhruti Maheshwari
Gonadotropins with IUI
The IUI treatment with Gonadotropins is suggested by the fertility experts for women who ovulate irregularly or who do not ovulate at all. The IUI treatment with Gonadotropins is necessary after taking some tests like hormone level, the transvaginal ultrasounds in order to increase the success rate of getting pregnant. Your fertility expert will suggest you these tests.
In order to stimulate the ovaries, Gonadotropins are necessary. And the main goal of luteinizing hormone and follicle stimulation hormone is to stimulate the ovaries enough to produce one good egg. The luteinizing and follicle stimulation hormone are the combination of Gonadotropins. In order to stimulate the ovarian follicles, your fertility expert will inject these two drugs into the body. This will ultimately increase the actual cost of IUI treatment by up to Rs. 40,000.
IUI Treatment Cost in Amroha with Success Rate
|Treatment||IUI Success Rate||Minimum Cost (Rs.)||Maximum Cost (Rs.)|
Factors That Influence IUI Cost in Amroha
There will be different cost of IUI in Amroha as it will depend on different factors including the couple’s age, their medical history, their type of infertility and also on different plans, medications and clinics.
Number of Cycles
The average of 10 to 20 percent of woman is successful who are below 30 years. The IUI success rate decreases as the age of the woman increases, the success rate will be 10 percent for woman who is between 30 to 40 years and maximum 5 percent who is 40 years and above. The fertility doctors will charge you for a single IUI cycle and so the cost will be higher for multiple cycles.
Age of Woman
The cost and the success rate both are depending on the age of the woman. The cost of IUI treatment for younger woman is low and the cost for the older woman is higher.
Medications for Ovulation Stimulation
The oral medications for ovulation stimulation are much affordable than the injections and it can cost from Rs. 650 to Rs. 6500 per cycle. If you are taking the oral medications, the IUI process cost will increase. Depending on the required dosage, the average price of oral drugs named as clomifene can range from Rs. 650 to Rs. 6000. You need to spend around Rs. 2500 per cycle for medications for stimulating the ovulation.
Along with the follicle monitoring and development during the treatment, a series of 3 or 4 ultrasound scans are carried out this increase the cost of IUI. This series of test will increase the IUI cost in Amroha by Rs. 2000 to Rs. 6000 depending on the clinic.
How Successful is IUI Treatment in Amroha
The success rate of IUI fluctuates. The success rate of the IUI will increase by 20 percent if the couple performed it every month. Hence, the success rate of IUI treatment in Amroha varies greatly due to fertility drugs used by doctors, the type of infertility and the age of female partner.
When IUI is performed it is less expensive and needs no surgical invasion, thus, it also offers low pregnancy rate than those who undergone through IVF. When the IUI treatment is completed, your IVF doctor will suggest few tips as the best after IUI care to enhance the chances of conceiving.
Nowadays, in a hectic life schedule, people lack in maintaining their health. Several problems are arising due to a stressful lifestyle. The issue of infertility is rising rapidly in males,…
IVF, In Vitro Fertilization, has been around from past few years but until a few years ago, many considered it as a complicated infertility treatment procedure. The procedure was previously…
IVF, In Vitro Fertilization, is a treatment used to cure the problem of infertility primarily. Whether the problem of infertility is related to the male or female, the treatment can…
Other Areas IUI Cost
- IUI Cost in Delhi
- IUI Cost in Mumbai
- IUI Cost in Chennai
- IUI Cost in Hyderabad
- IUI Cost in Kolkata
- IUI Cost in Bangalore
- IUI Cost in Warangal
- IUI Cost in Agartala
- IUI Cost in Agra
- IUI Cost in Aligarh
- IUI Cost in Allahabad
- IUI Cost in Ayodhya
- IUI Cost in Azamgarh
- IUI Cost in Bahraich
- IUI Cost in Ballia
- IUI Cost in Banda


The LISA Movie
This movie shows the design and operating mode of LISA. You will see the launch of three spacecraft with a Delta rocket, separation, orbit deployment, initiation of the laser beams as well as some detailed views inside the LISA satellites. Please click on the preview image to start the playback.
Credits: AEI/MildeMarketing/Exozet - Download: Movie Stills


Feb 20, 2017
Running on Rooftops celebrated our second anniversary this year, and to celebrate we are doing a number of interviews on the idea of fandom. We will be conducting a few interviews with some people in the online comic book community about doing geeky things and what being a fan means to them. These interviews will go over what they do, why they do it, and how they've grown from the experience.
Interview with CoffeeNCosplay
We had the pleasure of talking with Jenny, also known as CoffeeNCosplay. She is a cosplayer on the west coast, a big fan Cloak and Dagger, and a delight to talk to. We talk about cosplaying, the new Cloak and Dagger series, making costumes and how she's grown as a person. Have a listen!


Twitter claims Cross Firing at the Sialkot Border
Throughout Tuesday, the news was rife with reports of Line of Control violation by Indian Air Forces and the subsequent payload drop at Balakot. While India claims 350 militants of JeM, a militant group that took responsibility for the Pulwama attack, have been targeted and killed, Pakistan has assured that there were no casualties.
Foreign Minister of Pakistan, Shah Mehmood Qureshi, issued a strong statement following India’s excursion stating that Pakistan will retaliate at a time and place of it’s choosing.
Past midnight on Tuesday, while news channels aired routine programs, many people took to twitter to report that heavy firing is taking place across the Sialkot border. The news is as yet unverified by the government and credible news channels.
It is quite possible that people are trying to raise hue and cry, considering the already tense political situation. The hashtag ‘#Sialkot’ has already replaced ‘#IndianFailedStrike’ for the number one trending spot on Twitter.


Flambeau Gun Maintenance Box
GUN MAINTENANCE BOX Organize your gun cleaning supplies, extra chokes and tools in Flambeau's Gun Maintenance Box for portable service in the field or gun range. Gun pillar rest holds rifles secuely during cleaning and sevice.
Compact gun cleaning system. Four cleaning system. Four cantilever trays store cleaning supplies. Two locking support arms hold gun while cleaning. Label system provides storage customization. Organizes gun cleaning supplies and makes a great maintenance station.


No matter how fast they are, rules and regulations mean there's always the potential for race cars to go faster. Having withdrawn from the World Endurance Championship (WEC) last year, the boffins at Porsche have set about squeezing all the potential from the all-conquering 919 Hybrid.
The resulting 919 Hybrid Evo has set a new lap record at Spa Francorchamps, besting the time set by Lewis Hamilton in 2017.
Neel Jani, works driver, lapped the legendary circuit in 1:41.700, with an average speed of 245.61km/h and a top speed of 359km/h. By way of comparison, Hamilton laid down a 1:42.553 during qualifying last year.
So, how does the Evo differ from the 'regular' 919? To start with, it's been treated to a host of upgrades initially designed for the 2018 WEC season.
Such is the pace of development in world motorsport, the team was working on the follow-up to its 2017 car before the high-ups in Stuttgart decided to pull out – rather than waste that effort, those changes have been fitted to the Evo.
WEC fuel-flow regulations previously limited the V4 petrol engine to around 500hp (373kW), and capped the electric motor at around 400hp (298kW). Now, they're making 720hp (537kW) and 440hp (328kW) respectively.
Along with the uprated powertrain, the car has a new front diffuser and rear wing, both of which are now actively controlled. The underfloor turning vanes have been revised, and the fixed-height side skirts are new for 2018. As a result, the Evo creates 53 per cent more downforce than before, and boasts a 66 per cent better efficiency.
Finally, the loss of non-essentials like air conditioning, windscreen wipers, sensors, race-control monitors and a pneumatic jack has shaved a handy 39kg.
Having given Hamilton a bath at Spa, the Porsche team plans to tackle the Nurburgring and Laguna Seca on its 919 Tribute Tour.