text:
A P u b l ic At i o n o f T he R es e aR c h I nsT I T u T e aT naT I o nw I d e c h I l d Re n’s h o sp I Tal
Might a Defective Signaling
Pathway Lead to Left-Sided
• Genetics of Heart Defects
• Classifying Concussions
• Disarming Killer T Cells
• Bypassing the Brain’s Barrier
research is dedicated to the
mission of informing and inspiring Table of Contents
readers by highlighting scientific
performance at The Research Institute
at Nationwide Children’s Hospital.
This publication is produced
biannually by the Marketing and
Public Relations Department at
Nationwide Children’s Hospital.
fe at ure s
4 Genetics of Heart Defects
Molecular proof that three distinct cardiac defects share an origin
le a deRs hIp
8 Classifying Concussions
The Research Institute at Risk factors help predict how concussed kids will recover
nationwide children’s hospital
John a. Barnard, Md 12 Tracking the Mysterious Death of Killer T Cells
President Could a mechanism for silencing immunity improve the outcome of viral
lauren o. Bakaletz, phd gene therapy?
Vice President, Basic Sciences Research
Kelly Kelleher, Md, Mph
Vice President, Health Services Research
14 Bypassing the Brain’s Barrier
A new strategy evades a biological obstacle to gene therapy success
william e. smoyer, Md
Vice President, Clinical and Translational Research
e xt ras
Grant Morrow III, Md
7 A Home to National Clinical Trials
daniel R. Mann Nationwide Children’s Hospital has been selected to join two new clinical
Vice President, Research Administration
and Operations research trial networks, a designation bestowed only to preeminent
Katherine s. Milem
research facilities in the nation Injection of a gene therapy virus,
President, Research Business Services AAV9, successfully bypassed the blood
11 Research on the Road brain barrier and targeted neurons,
the carriers of electrical signals in the
research New mobile research lab targets hard-to-reach participants
nervous system, and astrocytes, the
Writer and editor
most abundant cells in the nervous
Melissa hamilton 16 Technology in Practice
system. Neurons that were successfully
Art Director A risk-assessment technology developed at Nationwide Children’s is
Tanya Bender infected by AAV9 are shown in yellow;
helping physicians and patients communicate more effectively
infected astrocytes are teal.
ON THe COveR The finding that AAV9 efficiently enters
Kim L. McBride, MD, examines Notch protein distribution throughout the interior and on the nervous system after injection into
Manager, Research Communications the surface of a cell. New research shows that changes in Notch signaling could promote the bloodstream provides potential for
Jan arthur heart defects.
new therapies and could lead to better
Contact us at understanding of neurological disease.
research | 3
Genetics of Heart Defects
PROOf THAT THRee DIsTINCT CARDIAC DefeCTs sHARe AN ORIGIN
Knowing that LVOT malformations share a common molecular
mechanism is a big step forward… – DR. K I M L . MC B R I De
valve stenosis, coarctation of the aorta seARCHING fOR A GeNeTIC LINK Families with at least two members with
and hypoplastic left heart syndrome. Since Dr. McBride’s group has established an LVOT malformation were included
Although all three conditions involve that there is a strong and complex genetic in the study and each underwent
the left side of the heart, a molecular component to LVOT malformations, their echocardiography to assess for any
similarity between the three defects had focus is now to pinpoint the genes behind structural heart abnormalities. After
not yet been identified. the disorders. Using a variety of study analyzing DNA markers from these
designs for gene mapping, the team is families, researchers found evidence for
During the study, which appears in
analyzing the pattern of inheritance of linkage to three chromosomes for the
Human Molecular Genetics, 91 patients with
selected genes in signaling pathways combined LVOT malformations and for
LVOT malformations had their DNA
important in cardiac development. the disorders individually.
screened for mutations in NOTCH1, a
gene that has been linked to an aortic Most recently, they conducted the first- These data provide the initial phase
valve condition and that is part of a ever study to “gene hunt” among families for gene identification of these LVOT
signaling pathway involved in multiple with multiple LVOT malformations, malformations, a basic-science discovery
Like a windstorm that leaves one household Despite the myriad of mutations that
could be responsible for each of the LVOT
developmental processes. These patients’ grouping the malformations together as that could be translated into improved
DNA was then compared to that of 216 though they were one disorder. “Grouping patient care. “Identifying a specific
without power, another with downed trees malformations, faculty members at The people without LVOT malformations. the individual malformations together as gene also now holds hope for eventually
Research Institute are discovering that the one disease allowed us to greatly increase
and a third with roof damage, scientists are most telling explanation of disease devel- Results showed that NOTCH1 gene
the ability to map the locations of the
providing better risk counseling for
families,” said Dr. McBride.
opment could be revealed by studying the mutations are present in some individuals
finding that congenital heart conditions can have disorders together as a group. with aortic valve stenosis, coarctation
responsible genes,” said Dr. McBride.
differing effects, yet stem from a common “Clinicians traditionally thought of
of the aorta and hypoplastic left heart
syndrome. With the help of Dr. Susan
biological event. these heart defects as separate entities,”
said Kim L. McBride, MD, principal
Cole, assistant professor in the College
of Biological Sciences at The Ohio State
investigator in the Center for Molecular University, several of these mutations 1) Notch1 protein distribution
THe MysTeRy Of LefT-HeART the first few days of life, many newborns and Human Genetics at The Research (green) as it appears normally,
MAlforMAtionS were shown to affect Notch pathway
with an LVOT malformation, especially Institute. “More recent views have throughout the cell interior and
Congenital cardiovascular malformations signaling in the cell. This suggests that
those with hypoplastic left heart grouped them together based on findings on the cell surface.
are among the most common birth Notch signaling plays a vital role during
syndrome, will die. from cardiac developmental biology, cardiovascular development and relatively 2) Distribution of mutant
defects in the United States. One group observations of clustering in families, Notch1 protein (green) trapped
Presumably, these defects arise when minor changes may promote LVOT 1) 2)
of heart defects known as left ventricular and our own previous work on near the cell’s nucleus (blue).
the inner lining of the heart or aorta defects. “These findings support our
outflow tract obstruction (LVOTO) inheritance analysis.”
develops improperly, but the basic, previous idea that these defects may
malformations arise from obstruction of CONsequeNCes Of A TRAPPeD PROTeIN
disease-causing mechanisms remain LINKeD By A MOLeCuLAR share a common developmental
blood flow through the developing left How could minor changes in the Notch protein sequence promote heart defects?
unclear. Scientists believe they are likely MeCHANIsM pathogenesis,” said Dr. McBride. “They
ventricle and aorta. These malformations Recent research has shown that some mutations in the NOTCH1 gene affect
a complex mix of defects in one or more Research conducted by Dr. McBride and also emphasize the hereditary nature of
include aortic valve stenosis, coarctation where the protein appears in the cell, trapping it and making it non-functional.
genes, chromosomal abnormalities and colleagues reveals, for the first time, a these defects and explain why one can
of the aorta and hypoplastic left heart
possibly environmental exposures. common molecular mechanism for aortic find individuals in the same family with
syndrome. Without major surgery during
different forms of LVOT malformations.”
4 | research research | 5
Biology and Consulting
has been selected to
join two new clinical
research trial networks, one
through the Muscular Dystrophy
Association and the other through
the Cystic Fibrosis Foundation.
This designation is bestowed only
host Interactions with to preeminent research facilities in
the nation. Clinical trial networks
bring together clinical research
centers throughout the nation to
Collaborative research between Kim L. McBride, MD, and Susan Cole, PhD, are revealing new information about how pediatric heart centralize and standardize the
some heart defects develop.
network research process.
sCIeNTIfIC TRANsLATION Dr. McBride also collaborates with better view of our target,” said Dr. Faculty members at Nationwide
THROuGH CLINICAL clinical faculty at Nationwide Children’s McBride. “Knowing that LVOT Children’s also serve on more than
collAborAtion including surgeons who provide heart malformations share a common
Blood cancers 40 study sections of national review
In order to progress toward gene tissue samples donated by patients during molecular mechanism is a big step
panels across a full range of pediatric
discovery, Dr. McBride’s team must cardiac surgery. “It would be impossible forward, as it allows us to more
maintain the clinical collaborations to conduct this research without the effectively focus our efforts, provides Gastrointestinal cell health topics. Section members are
that have been so vital in their present teamwork of our on-site surgeons the first clues to the underlying and Molecular Biology considered experts in their field and
research. While Dr. McBride’s team because the tissue samples are too fragile pathogenesis, and hopefully will allow assess the scientific and technical
utilizes animal models during their to be shipped from one location to improved genetic counseling for affected merit of research conducted by
studies, no existing animal models another,” said Dr. McBride. “It also helps families.” their peers.
precisely mimic LVOT malformations. that we are able to collaborate with Further reading: McBride KL, Riley MF, Zender
This is why much of their research doctors who are leaders in the treatment GA, Fitzgerald-Butt SM, Towbin JA, Belmont JW,
directly involves real-life patient samples. Cole SE. NOTCH1 mutations in individuals with
of hypoplastic left heart syndrome.”
left ventricular outflow tract malformations reduce
ligand-induced signaling. Hum Mol Genet. 2008 Sep
The complex nature of this translational Ultimately, the genetic information 15;17(18):2886-93. Web exclusive
work necessitates close collaborations
with a variety of skilled people including
obtained by Dr. McBride and his
McBride KL, Zender GA, Fitzgerald-Butt SM, Faculty members at nationwide To view a full list of national
colleagues may result in genetic tests
a genetic counselor who recruits patients to identify at-risk pregnancies early and
Koehler D, Menesses-Diaz A, Fernbach S, Lee K,
Towbin JA, Leal S, Belmont JW. Linkage analysis of children’s serve on more than 40 study review panels that include experts
from Nationwide Children’s
left ventricular outflow tract malformations (aortic
and families, obtains detailed medical
and family histories and collects blood
help develop unique treatments and
improved surgical techniques.
valve stenosis, coarctation of the aorta, and hyp- sections of national review panels across Hospital, visit us online at
oplastic left heart syndrome). Eur J Hum Genet. 2009
for lab studies. This information then
“Although we are at the beginning of our
a full range of pediatric health topics. www.NationwideChildrens.org
− keyword search: panels.
becomes part of an extensive clinical
hunt for the causes of these devastating
database that serves as a repository for
heart malformations, we now have a
6 | research research | 7
Although these mild brain injuries are common among children, Yet, additional research suggests there might be more at work.
Dr. Yeates says that not all concussions should be treated equally. “Given the amount of time kids spend with their parents and
“There is often an assumption that all mild head injuries are the in the family setting, it seems possible that these are factors
RIsK fACTORs HeLP PReDICT HOW CONCusseD KIDs WILL ReCOveR same, that all concussions are the same. But, conventional in recovery,” said Dr. Yeates. “Is it the injury that accounts for
definitions of concussion and mild head injury actually encompass post-concussive symptoms? Or is it other factors like how the
a wide range of severity,” he said. family copes or how the child reacts? What we’re finding is that
This wide range of severity can range from injuries that lead to
a 20-minute loss of consciousness and obvious lesions on brain One of Dr. Yeates’ studies examined how family burden and
imaging, to those that only involve feeling foggy, without being parent distress following a child’s mild traumatic brain injury
unconscious, and no findings on neuroimaging. Yet the level related to post-concussive symptoms. Overall, the results were
of severity is not the only determinant of patient outcome. “It’s encouraging, suggesting that family burden and parental distress
clear clinically that some kids with brain injuries do surprisingly following mild traumatic brain injury is typically limited. How-
well and others do very poorly,” said Dr. Yeates. “Although there ever, data suggested that children’s post-concussive symptoms
is a relationship between how severe an injury is and how kids shortly after a minor injury may be a more powerful source of
do, there is a lot of variability,” he said. post-injury family burden and distress than the injury itself.
WHeN CONCussION syMPTOMs LINGeR In conjunction with the University of Cincinnati, Dr. Yeates’
In an effort to clarify risk factors related to concussion outcomes, team is examining a potential intervention that uses a web-based
Dr. Yeates and colleagues recently examined nearly 200 children tool to teach families and children with severe traumatic brain
with concussion and followed them for a year. The study, which injury better problem-solving and communication skills as a way
appears in Pediatrics, revealed that while most kids had few prob- of reducing the parents’ distress and indirectly improving the
lems, one out of every four experienced significant post-concussive children’s outcomes. “Our research suggests that it is important
symptoms, some of which never fully resolved. “There is a group to do family-centered care, not just because it sounds like it is
of kids that are at risk and do seem to be able to continue to have the nice thing to do, but because it actually makes a difference
these symptoms even up to a year after their injury,” said Dr. Yeates. in how kids recover,” he said.
Still, he says this study is not cause for alarm. In reality, it
provides reassurance for parents of kids who suffer first-time
concussions because more often than not children recover fully
within a short amount of time. Despite this, the study also shows
that kids who are at risk because their concussions are more
Keith O. Yeates, PhD well-known, albeit unfortunate story among Dr. Keith Yeates’ family is that he toppled down
severe need to be monitored for a longer period of time as their
the stairs in a mobile baby walker during childhood. Although he was not evaluated for head
symptoms may last longer.
trauma, the fall left him with two prominent black eyes, which Dr. Yeates assumes were the
result of a basilar skull fracture. However, physicians aren’t always able to predict who will have
long-term issues. While symptoms like headaches, fatigue and
The clinical neuropsychologist and director of the Center for Biobehavioral Health at The
irritability can all be signs that a concussion is lingering, there is
Research Institute cites this childhood tale as a personal example of how head trauma and its
no test to show when a child has fully recovered.
potentially long-lasting effects are not so easily identified.
Dr. Yeates believes classifying concussions as high-risk or low-risk
Fortunately, his almost 20 years of clinical and research experience at Nationwide Children’s Hospital is helping
may help physicians determine which patients need special atten-
to reverse this reality. By studying brain development and outcomes of brain injury, Dr. Yeates and his team are
tion. “We’re trying to understand the factors that relate to recovery.”
working to help physicians and families understand risk factors associated with traumatic brain injury and their
expected outcomes. INjuRy seveRITy PLus fAMILy DyNAMICs
As previously indicated, one recovery-related factor seems to be
In relation to concussions, one of the most common childhood head injuries, researchers are learning that
severity of injury. Results from the aforementioned study showed
multiple physical and psychosocial factors play a role in how children will recover. Medical imaging techniques such as MRI help clinicians determine
that children whose concussions resulted in a loss of consciousness,
the severity of injury by revealing brain abnormalities related to
CHARACTeRIsTICs Of CONCussION disorientation or post-traumatic amnesia, or an abnormal MRI were trauma. Injury severity is one of the many recovery-related factors
A concussion is a mild injury to the brain caused by a blow to the head. It’s estimated that more than a half more likely to have symptoms that persisted. that Dr. Yeates’ team is examining in order to help classify
million kids in the United States go to the hospital each year with this injury, an average of a kid per minute, concussions as high- or low-risk.
every minute of every day.
8 | research research | 9
Research on the Road
THe effeCTs Of BRAIN AGe Dr. Yeates says that in a more severe diffuse injury that tends to
Research has also revealed that age is an important factor related involve large regions of the brain, young kids actually don’t recover
to recovery. When it comes to brain injury, kids shouldn’t be as quickly or as completely compared to older children. More
compared to adults. research is needed to find out if the effects of mild traumatic brain NeW MOBILe ReseARCH LAB TARGeTs
injuries are also more pronounced for younger children. HARD-TO-ReACH PARTICIPANTs
Consider this: Several studies that have focused specifically on
adults with mild traumatic brain injury indicate that the presence The vulnerability of age is why it is important to investigate emographics are an important The mobile lab is currently being used to
of the APOE ε4 allele, a genetic risk factor, is associated with the effects that brain injuries have on aptitudes developed measure for ensuring that research extend Dr. Reynolds’ impulsivity research,
poorer neurobehavioral outcomes. However, after conducting a during childhood, such as social skills. An ongoing study in findings are generalizable to large which focuses on how specific impulsive
similar study in children with this allele, Dr. Yeates and col- the Center for Biobehavioral Health is focused on social populations. How can researchers increase behaviors are involved in an adolescent’s ability
leagues found that the APOE ε4 allele is not consistently related outcomes related to traumatic brain injury. “A lot of traumatic a study’s demographic scope when it’s to stop or reduce smoking. Initial “on-the-road”
to the outcomes of mild traumatic brain injury in children. brain injury research has focused on kids’ cognitive skills, but logistically difficult for a wide variety of data collection began in January 2009 in the
the things that are most troublesome to kids and to their families people to participate? Ohio Appalachia region.
Despite the fact that childhood brain injury needs to be evaluat-
have to do with how kids do behaviorally and socially,” said Dr.
ed differently than similar injuries in adults, Dr. Yeates says there They can go the distance. Plans call for the mobile lab to be used
Yeates. “If you look at long-term predictions of how people turn
are more important age groups to compare. “There has been a for the next 10 to 15 years in studies by
out as adults, their social relationships as kids are better In an effort to improve sampling and to reach
lot of research in age-related differences in outcomes and the additional researchers, including research
predictors of quality of life than school performance is.” target populations, Center for Biobehavioral
most significant difference isn’t between school-aged kids and on parent safety practices and impulsivity
adults. It is between preschool children and older children.” To aid in both cognitive and social development following brain Health Principal Investigator Brady Reynolds,
and another focused on depression and teen
injury, investigators in the Center for Biobehavioral Health, in PhD, has developed a “research lab on
smoking. “The opportunities for research
conjunction with the University of Oregon, also are studying wheels.” This mobile lab is fully equipped
are endless,” says Dr. Reynolds.
No Way to Play the outcomes of a school transition program that alerts schools
when kids are coming back with traumatic brain injury, and
to conduct studies off-site, in rural areas
where participant recruitment is difficult.
KIDs ARe COMPeTING TOO sOON providing the school with appropriate resources.
A MODeL Of BRAIN ReCOveRy
A study from the Center for The identification of risk factors that help to predict how
Injury Research and Policy at patients will recover from brain injury, and a better understanding
The Research Institute found that of how kids are affected post-injury, could change the way
41 percent of student athletes
across 100 US high schools who
physicians and families deal with all-too-common concussions.
The findings could also help inform models of recovery in other Inside the Mobile Lab
diseases that can affect the central nervous system, such as
suffered a concussion returned to Every aspect of the mobile research lab was care-
childhood cancer or prematurity.
play too soon, against guidelines fully designed and strategically planned to utilize
Yet Dr. Yeates notes that as important prediction and aftercare space and protect privacy during data collection.
set by the American Academy of
are, methods of prevention should not be overlooked. “The
Neurology. In girl’s volleyball and PRIvATe BATHROOM
biggest difference we could make in terms of disability and
boy’s basketball and baseball, Space to collect urine samples to test for biomarkers.
death for kids in the US would be doing a better job of
more than half of the concussed Such tests are more reliable than personal reports
when measuring levels of cigarette smoking.
players returned to play before
Further reading: Yeates KO, Taylor HG, Rusin J, Bangert B, Dietrich A, Nuss
fully recovered. K, Wright M, Nagin DS, Jones BL. Longitudinal trajectories of postconcussive COMPuTeR CeNTeR
symptoms in children with mild traumatic brain injuries and their relationship to A place for participants to complete specially-
acute clinical status. Pediatrics. 2009 Mar; 123 (3): 735-43.
designed research tasks.
Web exclusive Ganesalingam K, Yeates KO, Ginn MS, Taylor HG, Dietrich A, Nuss K, Wright
For “Concussion Tips and M. Family burden and parental distress following mild traumatic brain injury in INTeRvIeW sPACe
children and its relationship to post-concussive symptoms. J Pediatr Psychol. 2008
Symptoms: What Every Parent A private room used during one-on-one data
Should Know,” visit us online at collection.
Moran LM, Taylor HG, Ganesaligam K, Gastier-Foster JM, Frick J, Bangert B,
Dietrich A, Nuss KE, Rusin J, Wright M, Yeates KO. Apolipoprotein E4 as a OuTDOOR AWNING
− keyword search: concussion. predictor of outcomes in pediatric mild traumatic brain injury. J Neurotrauma.
2009 Feb 18. [Epub ahead of print] Provides shelter for conducting research or
recruiting outside the lab.
10 | research research | 11
CH3 O CH 3
N CH3 O CH
surprisingly, instead of ridding the
cell of the foreign protein, killer
1. scientists deliver presence of the green N T cells receive a mysterious
fluorescence, which can The immune system recognizes eGFp as foreign
CH3 death signal and begin
a “gene” to the leg muscle 3. CH3
of a mouse model using aCH
be observed by the OH and killer T cells invade to destroy green to die. Their death
naked eye, confirms muscle cells.
viral vector. In this case,
N CH3 leads to gene
that the viral vector therapy success.
the gene N
N CH3 successfully delivered OH
Illustration by Anthony Weiler
H O the gene and that the
H desired protein is
that flouresces green. OH
Tracking the Mysterious CH3
N CH3 CH3
To Dr. Walker and
his team, these findings
O Death of Killer T Cells
CH CH3 O N
3 OH were reminiscent of studies in
CH3 humans infected with the hepatitis C
CH3 O virus. Dr. Walker’s team discovered that the
NeW ReseARCH Is sHOWING THAT GeNe THeRAPy DOes NOT evADe THe O CH3 OH
CH3 killer T cells lost the ability to destroy tissues they
IMMuNe sysTeM, As ORIGINALLy BeLIeveD. RATHeR, GeNe THeRAPy suCCess recognized as foreign and ultimately died, a process that
ReLIes ON THe DeATH Of IMMuNe-sysTeM-ACTIvATeD KILLeR T CeLLs. CH3 has been observed in N liver of humans persistently infected with
the hepatitis C virus. CH3
hat if your immune system could be switched on and “Some of these pathogenic adversaries have learned to use these Like an aircraft dropping needed supplies, scientists hope
N that N
OH BALANCING ACT
N off as needed to fight disease? immune switches to gain an advantage during infection, said
CH3 vectors can be used to deliver the body’s missing genes. OHHCH
C 3 These studies indicate that the balance between success and failure
Christopher M. Walker, PhD, director of the Center for Vaccine OH
However, one potentially important barrier to this success in gene therapy is considerably more tenuous than first thought,
Although this scenario might seem suitable for a
OHdramatic screenplay, in reality, scientists are edging closer to and Immunity at The Research Institute. “The hepatitis C virus could be the immune system. “Therapeutic proteins produced in relying on death of armed killer T cells. Unraveling mechanisms
is an example. It can exploit one of the off switches to impair diseased tissues differ from those inherited by the patient and so of killer T cell death may hold the key to treatment of diseases as
understanding how immunity is switched on and off during viral,
immunity in many infected people, resulting in life-long they may be viewed as foreign and threatening by the immune diverse as chronic virus infection, in the case of hepatitis C, and
bacterial and parasitic infection.
infection with the virus and greatly increased risk of serious system,” said Dr. Walker. success in gene therapy for inherited genetic diseases like muscular
liver diseases like cirrhosis and cancer.” dystrophy or hemophilia B.
Killer CD8 T cells are the most threatening component of the
In an effort to improve the health of patients infected with the immune system. These white blood cells were designed by nature “It is surprising how two lines of research for diseases that appeared
hepatitis C virus, Dr. Walker and his team are searching to “out- to destroy infected tissues and to interrupt production of new so dissimilar have converged in our laboratory,” said Walker.
smart” this pathogen and switch immunity back on. As is often the viruses. In gene therapy this normally beneficial response could “Understanding the switches that lead to programmed death of
case in research, this work has recently led Dr. Walker’s laboratory lead to disaster. T cells could at once allow us to restore immunity in a serious
in an unexpected and important new direction, one that could have infectious disease like hepatitis C, and turn immunity off where it
groundbreaking implications for gene therapy. A DesIRABLe fAILeD IMMuNe ResPONse is not wanted in gene therapy.”
Yet, disaster may not be inevitable.
GeNe-CARRyING vIRuses Moreover, this research serves as a reminder that current gene
Once considered futuristic, it is now possible to manipulate Remarkably, foreign proteins can be produced for a lifetime in therapy strategies involve a delicate balancing act with host
some simple viruses to deliver human genes. Through complex, mouse models without interference from the immune system. For immunity. “As these findings indicate, cellular immune responses
technology-assisted processes, scientists remove the disease-causing many years it was thought that these therapeutic proteins were should also be considered as a potential risk to the success of
genes from a simple virus and use the pathogen’s protective coating ignored by killer T cells, but recent studies by Dr. Walker’s team gene transfer when using viral vectors,” said Dr. Walker.
to package the functional human gene. challenge this logic. Delivery of an AAV vector to leg muscles of
Further reading: Velazquez VM, Bowen DG, Walker CM. Silencing of T
mice did result in long-term production of the therapeutic protein,
lymphocytes by antigen-driven programmed death in recombinant adeno-
Known as viral gene therapy vectors, these manipulated viruses have but instead of being ignored the protein engaged the immune associated virus vector-mediated gene therapy. Blood. 2009 Jan 15;113(3):538-45.
been shown to cure genetic diseases in animals and are now being system. Killer T cells even infiltrated the treated muscle, but failed
tested in humans. A common example is the adeno-associated virus in their mission to remove the muscle cells producing the
(AAV), which has been converted to treat inherited diseases including therapeutic protein.
Christopher M. Walker, PhD
cystic fibrosis, arthritis, muscular dystrophy and hemophilia.
12 | research research | 13

domain: biology


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Ghanaian rapper Ypee has acquired a brand new Range Rover in addition to his mansion and other fleet of cars.
Music seem to be paying off Ypee so well that, he is making a lot of properties from it. The Ghanaian super-talented rapper has acquired a brand new Range Rover on top of his Camaro and Benz car.
He took to Twitter and bragged a little about his achievement tweeting:
“Range!! Camaro!! Benz!! Mansion!! Don’t Try The Boy.”
Range!! Camaro!! Benz!! Mansion!!
Don’t Try The Boy🤣
Celebrities Buzz made moves to contact our folks closer to him, and we managed to get some exclusive photos of his assets.
The way and manner some Ghanaian rappers are making money through their career shows music is indeed paying off.
See the photos below:


text:
Please use this identifier to cite or link to this item:
|Title:||Cementifying fibroma of the maxillary antrum.|
|Citation:||Pathology 1994-10; 26(4): 499-500|
|Abstract:||A 26 yr old Caucasian, previously healthy, noticed a painless swelling of the left palate of 2 mths duration. On examination, a left maxillary swelling was noted with extension into the cheek. The mass was compressible. The CT scan revealed a large expansive tumor. Histological diagnosis of the enucleated lesion was cementifying fibroma. We describe a case of cementifying fibroma of the maxilla, an unusual location for this tumor.|
|Click to open PubMed article:||https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed//7892059|
|Appears in Collections:||(a) NT Health Research Collection|
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domain: medical


text:
19 Unique Mother Daughter Home Plans
19 Unique Mother Daughter Home Plans – There isn’t any reason you can’t place one in your home. When you’re creating home, constantly attempt to keep in mind that it’s not simply something you invest a bargain of money into. Your residence is a long lasting investment. As you are taking into consideration obtaining your house to seem bright as well as welcoming, you don’t want to exaggerate it or overwhelm your home wiring. While creating a new residence is commonly done as a long-lasting living choice, don’t neglect that the layout must be functional for when it’s the appropriate time to offer also. Moving, besides purchasing a new house includes a large amount of work as well as time, together with moving as well as shutting costs.
To start with, you can flip a residence. Your residence ought to remain in a place which allows for an organisation to run. You have your own home and you’re likely to get the choice to make it your means. Budget friendly homes can be accomplished by going through a residence builder.
Floor Plan Bungalow House In Philippines Luxury 24 Philippine from Mother Daughter Home Plans , source:bduburque.com
You constantly need to work to create a house that matches right into your area. Take into consideration the environment that you’re buying a home in, and what sort of basement you would such as. It’s very essential to comprehend all you can when purchasing a home. Semi-detached homes interest people wishing to have their own house together with the land it gets on. Therefore, if you’re contemplating building a brand-new home, you should assume seriously regarding whether you would love to dwell in a residence that’s larger than 2,600 square feet.
Your home was a whole mess. It’s not as difficult to obtain a home because you could believe. So you wish to build your very own residence on a little of land or make adjustments to your present home. You might utilize the steps below to construct your own rock residence.
Dimension When you’re starting to figure out how you want your home to look, remember the bigger the residence, the much more expensive it’ll be. However, it’s challenging to forecast to what degree your residence can cost you in future, but here are couple of general policies that vary, based on the general problems of your house, along with age. A three-bedroom home might be the best measurement for a vast collection of setups. Marketing an unfinished home might be an uphill task if the ideal choice isn’t taken. If you stay in an older home, then you most likely have ugly patterns on your ceilings.
Writing Fractured Fairy Tales Lapbook Planning Sheets Fairytale from Mother Daughter Home Plans , source:bluffbeachbooks.org
The absolute most critical portion of the plan is the windows. Since the plan is ready-made, all you require to do is to comply with together with the directions provided. Before starting making your very own plans, you need to have an excellent idea regarding the budget plan that you might manage to allocate and also the measurements of the bit of land, on which you intend to develop it. A professionally done flooring program could sound simple, but it can melt a massive opening in your pocket.
Your strategy was created just you. If you think of financing the strategy, you require to be well-prepared by taking into consideration several elements. After you are prepared with the harsh strategies, you discover it possible to begin producing a 3D floor program, using architectural software application that you locate on the internet. All you should be alert to is the very best way to find the optimal garage structure plans that will certainly create the process simple.

domain: design


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Man, 18-Year-Old Married To 71-Year-Old! [VIDEO]What The Biggest Age Gap Difference You've Dated? ~ @RatandPuffShow
THIS Pop Star Reportedly Got Married Over The Weekend!Congrats to THIS pop star, who reportedly got married over the weekend!
Jamie Lynn Spears Got Married!!Britney Spears took some time off from her Vegas show to be with her little sister, Jamie Lynn, who got married yesterday March 14!
It's Official! Bobbi Kristina and Nick Gordon Tie The Knot!
Kelly Clarkson Gets Married!
Is Chris Brown Being Faithful To Rihanna !?
Adam Levine Getting Married!?
Rihanna Wants Chris Brown To Propose
Can You Last As Long As They Did?
Can Joint Credit Hurt You Later?
Usher Engaged And New Girlfriend Is Preggers
Kringle Jingle 2017The Chainsmokers, Dua Lipa, Lauv.... Tickets on sale now....
MusicTown Will Celebrate Detroit's Music And CultureMusicTown will consist of a new broadcast studio, recording studio and performance space, in addition to national and local artist performances inside the intimate City Theatre adjacent to Hockeytown Café.
Kendrick Lamar to Perform at The Palace this JulyTravis Scott and D.R.A.M. will open.

domain: entertainment


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Little Russia (Mala Rus’, later Malorosiia). The name appeared in Byzantine sources at the beginning of the 14th century and was used for the church administrative unit covering the territory of the Principality of Galicia-Volhynia. In Byzantine documents and eparchy registers Halych metropoly (est 1303), consisting of six eparchies (Halych eparchy, Peremyshl eparchy, Volodymyr-Volynskyi eparchy, Kholm eparchy, Lutsk eparchy, and Turiv eparchy), was known as Micra Rosia (Little Rus’). From 1354 the name Macra Rosia (Great Rus’) was used for the 13 eparchies under the Kyiv metropolitan, namely, the Ukrainian eparchies—Kyiv eparchy, Chernihiv eparchy, Pereiaslav eparchy, and Belgorod eparchy—and 9 Belarusian and Russian eparchies. It was probably under the influence of Byzantine church nomenclature that Prince Yurii II Boleslav called himself Dux totius Russiae Minoris in a charter of 1335. Galician kings and princes usually used the title Rex Russiae, Dux totius terrae Russiae, or Dux et Dominus Russiae.
The name Little Russia does not appear in 15th- or 16th-century documents. Only in the first half of the 17th century did it begin to be used in church correspondence between Kyiv and Moscow. Until almost the end of the 17th century the names Rus’ (Latin: Russia), Ruthenian land (Polish: Ziemia Ruska) and Red Rus’ (Latin: Russia Rubra) were used in chronicles and maps to designate western Ukrainian territory. The term Great Rus’, which had been applied originally to the eparchies of Kyiv metropoly, was used later to refer to the territories of Novgorod the Great and then Suzdal and Moscow, although until the 18th century those territories were usually called Muscovy in books and maps. Great Russia was used by foreigners, however, to designate the Ukrainian state of Bohdan Khmelnytsky, whom they titled Master and Hetman of Great Russia (1650). After the Pereiaslav Treaty of 1654 Tsar Aleksei Mikhailovich added to the usual title of the Muscovy tsars the phrase ‘of all Great and Little Russia.’ Later the term Little Russia (Malaia Rossiia or Parva Rossia), as the designation of the Ukrainian territory united with Muscovy, began to be adopted in Ukrainian official documents, chronicles, and literature. The name does not appear on the geographical maps of Ukraine published by the Russian Academy of Sciences in 1736–8 or in the Russian atlas of 1745.
Malorossiia, which is derived from Malaia Rossiia, began to be used in official nomenclature in the 18th century to refer only to Left-Bank Ukraine, that is, to the Hetman state. In 1781 the Hetman state was abolished and replaced by Chernihiv vicegerency, Novhorod-Siverskyi vicegerency, and Kyiv vicegerency. In 1796 they were merged to form Little Russia gubernia (excluding Kyiv), which in 1802 was divided into Poltava gubernia and Chernihiv gubernia. The official terms Little Russia (Malorossiia), Little Russian (malorusskii), and Little Russians (malorossy) were used for Russian-ruled Ukraine and its inhabitants only in the 19th and at the beginning of the 20th century. Ukrainians living outside the Russian Empire were also called Little Russians. But the name Ukraine was also quite widely used in Russian scientific and literary publications. The name Little Russia was sometimes restricted only to Left-Bank Ukraine within the limits of Poltava gubernia, Kharkiv gubernia, and Chernihiv gubernia. After the Revolution of 1917 the terms Little Russia and Little Russian were dropped from general and official usage. Ukrainians did not approve of the term Little Russia, and it does not appear in Ukrainian folklore.
Hrushevs’kyi, M. ‘Velyka, Mala i Bila Rus’,’ Ukraïna, 1917
Solov’ev, A. ‘Velikaia, Malaia i Belaia Rossiia,’ Voprosy istorii, 1947, no.7
Borschak, E. ‘Rus’, Mala Rosiia, Ukraïna,’ Revue des études Slaves, 24 (1948)
Gregorovich, A. Ukraine, Rus’, Russia and Muscovy: A Selected Bibliography of the Names (Toronto 1971)
[This article originally appeared in the Encyclopedia of Ukraine, vol. 3 (1993).]

domain: history


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Using Phenotypic Heterogeneity to Increase the Power of Genome-Wide Association Studies: Application to Age at Onset of Ischaemic Stroke Subphenotypes
Traylor M., Bevan S., Rothwell PM., Sudlow C., Dichgans M., Markus HS., Lewis CM.
Genome-wide association studies (GWAS) have been successful in identifying common variants related to complex disorders. However, some disorders have proved resistant to this strategy with few associations confirmed, despite evidence from twin and family studies of a genetic component. Sophisticated strategies that account for phenotypic heterogeneity may be required to uncover these genetic contributions. Age at onset is an example of a potential source of this heterogeneity in ischaemic stroke. We explore the contribution of age at onset in the Wellcome Trust Case-Control Consortium 2 ischaemic stroke study. We first examine four established stroke loci in younger onset cases. We extend this to all single-nucleotide polymorphisms (SNPs) genome-wide, testing for stronger association signals in younger subsets of cases. Finally, we estimate the pseudoheritability accounted for by common SNPs present on genome-wide genotyping arrays for cases stratified by age at onset. We find evidence for stronger associations in younger onset cases for the four established stroke loci. Genome-wide, in cardioembolic and small vessel stroke subphenotypes, a significant number of SNPs show stronger association P-values when the oldest cases are removed. Finally, we show that the pseudoheritability estimated by common SNPs in cardioembolic stroke increased from 16.5% for older onset cases to 28.5% for younger onset cases. Our results indicate that age at onset is a valuable measure for case ascertainment and in analysis of GWAS in ischaemic stroke: focussing on younger cases who may have a stronger genetic predisposition increases power to detect associations. © 2013 WILEY PERIODICALS, INC.

domain: literature


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The punctuation on a series of Pentagon officials’ testimony about the “dangers” of possible budget cuts is the admission that they are launching a “far-reaching study” on whether they will still be able to start new wars against Iran and North Korea after the cuts.
All of this began with Defense Secretary Chuck Hagel admitting that the US Army is actually quite a bit bigger than it needs to be for “current missions,” and that they could save some $150 billion with cuts that would have a limited effect.
But no government agency is content to just stick to “current missions,” and to justify its ridiculously huge budget, the Pentagon is forever arguing about the needs to prepare for more huge wars that the president might decide to start.
Of course, the US has been threatening to attack Iran and North Korea for literally a whole generation now, and is constantly envisioning new wars the world over. The whole point of the sequestration fight is not to be a buzzkill for the military-industrial complex, but is rather a simple recognition that the US can’t afford constant wars and preparation for yet more wars on top of those wars.
Last 5 posts by Jason Ditz
- North Korea: Up to US If Summit Will Happen, Or Nuclear Showdown - May 23rd, 2018
- Pentagon Uninvites China From Joint Naval Exercises - May 23rd, 2018
- Iran Sets Out Conditions for Europe to Save Nuclear Deal - May 23rd, 2018
- Iranian Officials Split on Responding to US Demands - May 23rd, 2018
- Israel Considers Long-Term Ceasefire With Hamas - May 23rd, 2018

domain: news


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Every summer, I eagerly await the first ripe blueberries of the season to appear. Frozen berries are fine for the rest of the year, but when they are juicy and fresh, straight from the bush, they are simply heavenly. We always eat some of the berries fresh and then use the rest for pies and jam. (And if you love homemade jams and jellies, try my recipe for The Easiest Homemade Apple Butter.)
And every summer, I make my yearly batch of this Blueberry Lemon Jam because it’s one of my very favorite jams. It’s a sweet jam that’s also a little lemony and is perfect on toast, or as a topping for a cheesecake. (I even once made a couple of hundred tiny jars of this jam as wedding favors, and they were a bit hit!) And it’s not just lemon juice that gives it such a bright lemon flavor. A generous amount of lemon zest goes into every batch because that’s where the real lemon flavor comes from.
I know some folks prefer to make jam without pectin, but because blueberries are fairly low in naturally occurring pectin, I prefer to hedge my bets and use added pectin to help this jam to set. Plus, jam made without added pectin typically needs to cook longer than those with added pectin, giving the jam a more caramelized flavor. And while these kinds of jams are equally delicious, I like my Blueberry Lemon jam to have a fresh, bright flavor, so I go with the pectin.
I also use a moderate amount of sugar in this jam. There isn’t as much sugar in this recipe as you find in many traditional jam recipes, but it really needs the sugar to balance out the flavor because of the added lemon. Also, low-sugar jams will quickly lose their color and flavor in storage and are more likely to have a reduced shelf life and even develop mold shortly after opening. For this reason, when I want a very low or no-sugar jam, I will often freeze it, or make a small batch that goes straight into the refrigerator.
Of course, you can freeze this blueberry lemon jam, too – just freeze it in small jars, or look for small containers made especially for freezer jam that you can pick up nearly anywhere that canning supplies are sold.
If you are new to canning and would like to learn the process, rest assured that canning jam in a boiling water bath is safe and easy. Here are two references that will give you step-by-step instructions:
- http://nchfp.uga.edu/ – The National Center for Home Food Preservation at The University of Georgia offers a free online course that gives you the basics of at-home food preservation. I have taken this course and I highly recommend it!
- PickYourOwn.org – This website not only gives great instructions for canning and making jam, but it also gives information about local farms and orchards where you can pick your own fruits and vegetables in your area.
If you try this recipe, I hope you love it! Please let me know in the comments below.
*As an Amazon Associate I earn from qualifying purchases. This post may contain Amazon or other affiliate links, which means I will earn a commission at no additional cost to you if you click through and make a purchase.*Print

domain: food


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The road from sweetness to corruption is as easy as forgetting a giant cherry long enough for it to dry and dimple into a skull. At least that's what the Simon Costin sculptures that peppered the beige carpeted runway at Undercover seemed to say.
The opening felt sweet and innocuous enough, pretty gowns in pastel shades. But this is designer Jun Takahashi we're talking about, and before long, that Alice in Wonderland feeling proved to be more Tim Burton's than Disney’s.
Later backstage, the designer confirmed that he'd been thinking about innocence and corruption. Just in case the prints of Hieronymus Bosch's Garden of Earthly delights and those cherries, which were also paraded as clutches, with their hermetic loss of purity symbolism, hadn't been clear enough. It felt pretty strange to get what Takahashi was getting at so easily.
All that loveliness was delivered with a sly touch. The Japanese designer is fabulously talented at tailoring, and this is often overshadowed by the strength of his mise-en-scene. A tiny screen on a sunny yellow windbreaker is just the kind of twist expected from Takahashi's off-kilter designs. Smashed mirrors were embroidered on a flouncy party skirt hem, and echoed on a bag's screen. Like details in a haunted house, you could make them out of the corner of your eye; in a blink, they're gone. Shows like his - full of details that make you tick, and engage the brain - are increasingly few and far between. For Undercover devotees, there will be plenty to buy - the wood print dresses, a shrunken blouson as tight as a blouse worn with a long, full skirt in a matching print, a Bosch-printed shirt dress with a sharply feathered belt. For those who prefer a non-committal dip of the toe in, there is always the safety of his final black silhouettes. But that doesn't mean the pieces were staid. They had the ominous portend of a murder of crows, marching to Kate Bush's melancholy voice.
Takahashi has a wicked sense of humor. The jump from Bosch to Bush was an unexpected, if typical, split. That his pretty ballerinas turned into black swans by the time of the finale, though, was no surprise.

domain: artistic


VIDEO: Oritse Femi – “Make Am”
Nigerian most talented vibes maker, Oriste Femi drops the music video to the his released tunes track which titled “Make Am”.
Download & Watch “Make Am” Below:
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Tunisian international ,Anis Ben-Hatira, has been fired by Bundesliga club Darmstadt after he is suspected of being a financier of an Islamic terror group mainly active in Ghana, according to a publication on the credible Italian sports website, calciomercato.com.
Hatira, is suspected of funding Ansaar International e.V., a Salafi terror group which mainly operative in Ghana.
The President of Darmstadt Rudiger Fritsch has told German paper Bild that the player is not part of the team any more.
“We have analysed the situation and we have understood that it is not possible to continue our collaboration any more”, the club’s number 1 has told the German paper.
This news will come as great shock to many Ghanaians, who might not know about the activities of Ansaar International e.V., a Salafi terror group.
Hatira, is a former U-21 Germany International who won the U-21 European Championship in 2009. Despite playing with Germany youth teams, the winger has chosen to play for senior Tunisia national team.
Below is the link to the original story


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State of the art digitalization features Barco and Dolby technology
Cinema Equipment and Supplies – CE+S – the global leader in digital cinema solutions, announced that it was selected by Venezuela’s third-largest movie theatre circuit, Cinex Plaza, to lead the design and digitalization deployment across 60 screens nationwide.
Following a lengthy and competitive selection process, Cinex Plaza chose CE+S for its expertise in large-scale implementation of digital technologies and its superior service reliability. The digital cinema conversion for Cinex represents the last one of its kind for any large-scale circuit in Latin America.
“This is the most important and innovative project that Cinex Plaza has undertaken in recent times and we are thrilled to count on the support and collaboration of CE+S once again,” said John Parra, General Director at Cinex Plaza. “In today’s rapidly changing digital times, having the right partner by our side is fundamental to keep up with our commitment of excellence and service to our clients, the moviegoers.”
“Our partnership with Cinex Plaza is a testament to CE+S’ positioning as a global leader in digital cinema technologies and our commitment to theater owners to offer best-in-class customer service,” said Guillermo Younger, CEO at CE+S. “Clients around the world have put their trust in us to transform their operations into fully digital theatres and we are proud to collaborate with industry leading partners like Barco and Dolby in these deployments.”
CE+S is providing a 360-degree digital solution built on Barco and Dolby technology that will be pre-staged, assembled and tested at the company’s Miami headquarters before arriving at Cinex’ 60 screens in Venezuela. The full range of cutting edge products include Barco 10S and C model projectors, and Dolby’s latest Integrated Media Server, the IMS2000, as well as the CP750 Digital Cinema Processor.
As part of CE+S’s complete offering in digital cinema solutions, Cinex Theatres will be adding Cielo – CE+S cloud-based remote monitoring and technical support platform – to the full spectrum of services of this implementation. In 2015 Cielo marked a turning point in theater operations, allowing exhibitors to join the Internet of Things (IoT) era with a technology that allows them to proactively manage their business with unmatched mobility and real-time visibility.
Cinema Equipment and Supplies (CE+S) is a global leader in digital cinema solutions. For the past 30 years, CE+S has been a pioneer in delivering first-in-market innovative technology and its certified technicians have deployed over 1,500 digital cinema systems worldwide. In 2009, CE+S created the first home-grown tech support solution in Latin America and in 2015, it revolutionized the movie industry with the launch Cielo, a first-of-a-kind, cloud-based, remote monitoring and technical support platform developed for the Internet of Things (IoT) era. For more information, visit www.cinemaequip.com
About Cinex Plaza
Cinex Plaza is the third-largest movie theater circuit in Venezuela. The company was founded in 1944 and has remained a family-owned business ever since. Today, Cinex Plaza operates a network of 10 complexes and 60 screens across the country, located in the most premium shopping centers in Venezuela.


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Our Second Birth: Christian Reflections on Death and New Life
Henri J.M. Nouwen
, Henri J. M. Nouwen
Publication date: 2016-02-04
The inspirational readings of Our Second Birth throw light on the meaning of life, friendship, and the love of God, and are seen from the perspective of the life to come. Drawn largely from Sabbatical Journey, but newly packaged for devotional and gift markets, this volume is the newest addition to the attractive Crossroad Nouwen Library.Henri J.M. Nouwen, Henri J. M. Nouwen
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domain: library


TelePulse Oximeter is a small, electronic, handheld diagnostic device that you use at home to accurately measure the saturation level of oxygen in your blood (Sp02) and your pulse rate. SHL Telemedicine typically provides this device as part of a home – telemedicine system capable of routinely transmitting important medical parameters. System and services are usually provided to users suffering from chronic lung-heart diseases affecting saturation level, such as Chronic Obstructive Pulmonary Disease (COPD). Anyone can use this small, lightweight device, which requires no special training. It is ready for immediate use and requires no user adjustment. You simply clip it onto one of your fingertips, much as if it were a finger puppet. The SHL TelePulse Oximeter is a low maintenance device, powered by a rechargeable lithium battery. Along with TelePulse Oximeter, and as part of the service, you will also receive an SHL Central Communication Module (CCM).
- Other characteristics: : wireless
- Configuration: : compact, fingertip


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For the past few weeks and for the next several weeks, I’m studying the beatitudes found in Matthew 5:3-12. These are some of the most familiar words of Jesus. These are the “Blessed Are” statements, and one of the most interesting things about these eight promises of blessing is that the recipient of each blessing is so not what we would expect.
#1—the poor in spirit
#2—those who mourn
#4—those who hunger and thirst for righteousness
#6—the pure in heart
#8—those who are persecuted
While spiritually speaking, this might sound like a list of things to strive for, these words of Jesus, just like most of His words, go against the grain of our culture. So, we are left with this question:
What are we going to deem most important? The things that Jesus defines as priorities or the things of this world?
While there is much to pull from this list of eight, I want to pause today on #3:
“Blessed are the meek.”
For whatever reason, perhaps even due to ignorance, the word meek seems to come with a negative connotation. However, if Jesus holds this quality in high regard, it may warrant us spending a bit more time on it. Why do we associate meekness with weakness? Why do we assume that the meek are the ones who get walked all over and taken advantage of? Why do we think that we must flex our power muscles, even if it means bulldozing people along the way, in order to get what we want?
Let me offer you an accurate, Biblical definition of meekness, and let’s see if our perspective starts to shift a bit. Meekness is gentleness, humility, and power under control. Let that soak in for just a minute. Gentleness is one of the fruits of the Spirit. Humility was first and foremost embodied and exemplified through the life, ministry, and ultimately the death of our Savior Jesus Christ. And power under control? That doesn’t sound like weakness to me. It sounds like self-control, another fruit of the Spirit.
To be like Jesus is to be meek. At any moment in Jesus’ life and ministry, He could have struck every single person dead who opposed Him. But He didn’t. At any moment on that brutal cross, He could have called down upon the angels in Heaven and removed Himself from such torture. But He didn’t. At any moment in any given day, Jesus could lift His grace and mercy from our lives, those of us who continually turn to lesser things than Him and continually break His heart in our sin. But He doesn’t.
That is meekness. The ability to harness the power you have been given by tempering it with a perfect blend of gentleness and wisdom. I don’t know about you, but I want to be meek.
“Blessed are the meek, for they shall inherit the earth.” Matthew 5:5 (ESV)


Developer not getting way in Fort Mitchell
FORT MITCHELL – Brandicorp, the developer of the former Drawbridge Inn site in Fort Mitchell, isn’t getting everything its way in the city.
On Nov. 10, City Council denied the developer’s request for a zone change to the area that would permit first-floor residential units in the development. The original understanding, according to Mayor Chris Wiest, was that the first-floor would be used for commercial and retail, with high-end residential units on upper levels.
The Drawbridge project, now dubbed the Fort Mitchell Gateway, includes retail and residential development that will be anchored by a 75,000-square-foot medical office building by The Christ Hospital Health Network.
The Drawbridge Inn, the sprawling medieval-looking landmark, closed in late 2011 after 42 years in business. The 382-room hotel had struggled financially in recent years.
Mark Reitzes, a representative from Brandicorp, told council they were requesting the zone change for more flexibility.
“The attention we’ve been getting is less than robust,” Reitzes said. “That’s why we want flexibility. We’re working hard to get it marketed; we’re just not getting the attention we want.”
The mayor and council, however, were insistent that the first-floor space will be an easy sale to retail and commercial businesses.
“I can’t see it sitting vacant for long,” Councilman Dan Rice said. “It’s a prime piece of real estate.”
Wiest urged council to carefully consider the developer’s request.
“This is prime real estate with highway frontage,” he said. “In my opinion residential use (on the first floor) is a lazy way out of this development. Zoning is a council decision, the mayor has no say on zoning issues, but once this decision is made, I don’t think you can unwind it.”
Council decided unanimously, with the absence of members Dennis Zahler and Ray Heist, to not permit first-floor residential use. The governing body moved forward with the first reading of the zone request, omitting the language that included the first-floor residential use, but permitting drive-thru operations, parks and swimming pools for accessory use.
Holding back for future improvements
The council also approved second reading of an ordinance that sets up a tax increment financing (TIF) district to help assist with Brandicorp’s redevelopment.
The TIF district will include the former site of the Drawbridge Inn, Beechwood Mobile Community and Crescent Park.
Establishing a TIF district will allow the city to capture the incremental increase in taxes created by new development and use a portion of those taxes to improve the areas within the district to promote development, according to the city’s TIF consultant James Parsons. It will also give Brandicorp an opportunity to apply for state incentives.
Under the TIF, according to Parsons, an attorney with the Covington-based Taft, Stettinius and Hollister, the city is allowed to pledge up to 80 percent of the incremental revenue for 30 years.
Parsons said that the city can use the tax monies set aside for the TIF district to make public improvements to the area or offer incentives for certain projects, such as the Gateway development. Fort Mitchell is allowed to pledge the full 80 percent to just the Gateway development or can choose to pledge a certain portion of the 80 percent to the development and put the remaining percentage of profits toward other public improvements within the district.
Mayor Wiest again urged council to carefully consider the decision. He said that public improvements to the other areas within the TIF district could include better sidewalks, lighting and even a small community center.
“There’s lots of opportunity for the future of this area,” he said. “The developer, however, is going to want the full 80 percent. The developer is going to do what all developers do and try to get every dollar available from the incentives. That’s their job. My view has been to say no to that and hold back about a million dollars for these other possible improvements.”
Holding a portion of the 80 percent would not impact the Gateway development’s qualification for state incentives, Parsons said. However, he said, the city does have “to show the state that the city is making a significant investment.” Parsons said most cities do not hold back, but give the full pledge to public improvements that benefit the main development.
Parsons also noted that Kenton County and the Northern Kentucky Area Development District are not withholding any of their 60 percent pledge for 30 years.
Wiest suggested that the city hold back about $2 million for the city to cover public improvements to other parts of the TIF district.
“I don’t think that is going to blow up a $125 million project,” he said. “The question is do we want to get other things done in the community or not?”
Councilman Jim Hummeldorf suggested that the city give the full 80 percent at 20 years and collect the profits from the last 10 years, which equal to about $2 million. Council agreed on this breakdown of the numbers and Wiest said he would present the offer to Brandicorp.
Brandicorp representatives did not respond to the Recorder when contacted about the proposal.
Want to continue the conversation? Tweet @MStewartReports


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Heat a small skillet on high, and toast each of the tortillas in the dry skillet until they begin to blister. Remove tortillas from the skillet, wrap in aluminum foil and allow them to steam a bit. Hold until ready to assemble.
In a small bowl, mix yogurt with the juice and zest of a lime. Set aside.
In another mixing bowl, combine the cabbage, tomatoes, cilantro and cumin with the juice of another lime. Gently fold in cubed avocado. Set aside.
Over medium heat, add oil to the skillet. Add the tilapia filets, and sprinkle with chili powder and oregano. Flip the fish after about 4 minutes, and continue cooking for another 2 minutes, until firm. Note: You may have to cook in batches.
To assemble a taco, place half a tilapia into a warmed tortilla, add some of the tomato/cabbage mixture and top with a dollop of the lime yogurt.
Did you know the avocado is a fruit, not a vegetable? Learn more about the amazing avocado, including its rich history, cultural impact and tasty ways to eat this delicious superfood in guacamole as well as other dishes!
Add your phone number to receive the list of ingredients via text for your shopping list.
BAJA FISH TACOS
Amount Per Serving 8
Calories 220 Calories from Fat 0
% Daily Value*
Total Fat 11g
Saturated Fat 0g
Trans Fat 0g
Polyunsaturated Fat 0g
Monounsaturated Fat 0g
Total Carbohydrates 19g
Dietary Fiber 4g
Total Sugars 3g
Includes 0g Added Sugars
Vitamin A 0mg
Vitamin C 0mg
Vitamin D 0mg
* Percent Daily Values are based on a 2000 calorie diet.
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Jeanne Gerville-Réache (March 26, 1882 – January 5, 1915) was a French operatic contralto from the Belle Époque. She possessed a remarkably beautiful voice, an excellent singing technique, and wide vocal range which enabled her to perform several roles traditionally associated with mezzo-sopranos in addition to contralto parts. Her career began successfully in Europe just before the turn of the twentieth century. She later came to the North America in 1907 where she worked as an immensely popular singer until her sudden death in 1915. She is particularly remembered for her portrayal of Dalila in Camille Saint-Saëns' Samson et Dalila, which she helped establish as an important part of the repertory within the United States. She also notably portrayed the role of Geneviève in the world premiere of Debussy's Pelléas et Mélisande in 1902.
Jeanne Gerville-Réache was born in Orthez, France. Her father was the governor of the French Caribbean islands Guadeloupe and Martinique, and she spent her childhood in Martinique with him and her Spanish mother. She studied in Paris under Rosine Laborde through whom she met operatic soprano Emma Calvé, a former pupil of Laborde's. Calvé arranged for Gerville-Réache to make her professional opera début as Orphée in Gluck's Orphée et Eurydice at the Opéra-Comique in 1899. Mezzo-soprano Pauline García-Viardot coached her for this first production and then continued to teach her for the next several years.
Gerville-Réache was offered a permanent place at the Opéra-Comique in 1900 and she sang there through 1902. While there she sang roles in two world premieres, Catherine in Camille Erlanger's Le Juif polonais (1900) and the role of Geneviève in Debussy's Pelléas et Mélisande in 1902. Shortly after Pelléas et Mélisande, Gerville-Réache got in a heated argument with the Opéra-Comique 's director, Albert Carré, and she left the company. In 1903 she joined the roster at the Théâtre Royal de la Monnaie in Brussels where she appeared in five operas over the next two seasons. She made her debut at the Royal Opera House, London, in 1905 in the role of Orpheus.
In 1907, Gerville-Réache came to the United States for the first time to sing with the Manhattan Opera Company in New York City, where she performed roles until 1910. She notably reprised the role of Geneviève in the United States premiere of Pelléas et Mélisande (1908) and gave a critically acclaimed performance as Dalila in Saint-Saëns' Samson et Dalila. She also sang in the world premiere of Jan Blockx's De Herbergprinses (performed in Italian as La Princesse d'Auberge, 1909), and in the United States premiere of Richard Strauss's Elektra (1910) as Klytaemnestra, the latter of which she did not enjoy singing. In 1910 she married Georges Gibier Rambaud who was the director of the Pasteur Institute's branch in New York City.
From 1910 until 1912, Gerville-Réache sang with the Chicago Grand Opera Company and appeared in operas in Boston and Philadelphia. She portrayed such roles as Dalila, the title role in Bizet's Carmen, Brangäne in in Richard Wagner's Tristan und Isolde, and Fricka in Wagner's Die Walküre. From 1914 until 1915 she sang with the National Canadian Opera in Montreal.
Gerville-Réache died at the early age of 32 from food poisoning in New York City. Up to this point, everything had indicated a spectacular continuation of her brilliant career and the music community lamented the loss of what several critics had deemed "one of the most beautiful voices of the century". Her voice is preserved on several recordings made with Columbia Records and the Victor Talking Machine Company between 1908 and 1913. She left behind her husband and two sons. She has a great-great grandson and granddaughter living in America.
This article uses material from the Wikipedia article "Jeanne Gerville-Réache", which is released under the Creative Commons Attribution-Share-Alike License 3.0.


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'˜Turn it into a roundabout' say drivers of Fishergate's confusing bollard
IT'S the road feature which has left city motorists scratching their heads.
The stone pillar at the junction of Fishergate and Corporation Street in Preston city centre has been knocked over multiple times by confused motorists failing to negotiate the ‘shared space’.
Last week a silver Audi hit the pillar, knocking it over yet again.
The incident prompted a council official to stress that the bollard was not a roundabout.
The problem is that its positioning at the road junction within a circular area gives the impression it is - and some drivers treat it as one.
The Evening Post watched as motorists hesitated at the bollard - and many were confused whether to give way to pedestrians crossing their path.
Some stopped to let people across - others didn’t.
Business people in the area gave us their views. Anna Yiangou, manager at Mr Potato in Fishergate, said: “I’m a driver and it’s a roundabout as far as I’m concerned. People always seem to be crashing ito it - I’ve no idea why. Whatever it is, it’s there to be avoided. Why anyone would drive up onto it I haven’t a clue.”
Anna added: “They should put the traffic lights back. They’ve narrowed the road and made it very confusing for everybody.”
Rashid Patel, from Kingswood Sales and Lettings, said: “I see it happen about once a month.
“The council is wasting money fixing it, instead they should turn it into a roundabout because that’s what most people think it is.”
“It is a danger trap, a fatal accident waiting to happen and it makes my blood boil.”
Lucy Nicklin, of the nearby Tasty takeaway, said: “It’s very confusing. I’ve seen people go into it a couple of times. No-one seems to give way to pedestrians like they used to either.”
Another shop worker said: “It looks like a roundabout and that’s why people are getting confused. I think they should turn it into a roundabout and then people would know where to go.
“They should also have crossings as it’s not very clear for pedestrians and where to give way.”
Daniel Herbert, Lancashire County Council’s highways manager, said recently: “It is important to make it clear that there is not a mini-roundabout at the junction of Corporation Street and Fishergate. The junction operates as a T-junction, but giving equal priority to all road users, with drivers taking care and giving way as appropriate.
“The Fishergate scheme has been successful in encouraging most people to drive more carefully and safely through this area. Following the latest incident, we’re looking at ways to further highlight the road layout for drivers.”


The House of Representatives reauthorized the Foreign Intelligence Surveillance Act (FISA) Thursday, absent a proposed amendment intended to protect civil liberties.
The bill, passed by the House 256-164, extends section 702 of the FISA Amendments Act for six years. The statute entitles intelligence agencies to collect the communications of foreigners abroad without a warrant, even when the individual in question was communicating with an American citizen.
The House rejected the so called “USA Rights” amendment, which, among other things, prohibits intelligence services from using information collected incidentally on Americans absent a warrant. The rejected amendment attracted politically diverse opposition as libertarian conservatives like Sen. Rand Paul of Kentucky joined liberal Democrats in attempting to combat perceived government overreach.
President Donald Trump appeared to contradict the official White House position Thursday morning, criticizing the program and suggesting it played a role in the surveillance of officials on his presidential campaign. Trump walked back the tweet roughly two hours later, drawing a distinction between “unmasking” – a term used to denote the practice of revealing the identity of Americans who communicate with foreign surveillance targets – and the surveillance of “foreign bad guys.”
With that being said, I have personally directed the fix to the unmasking process since taking office and today’s vote is about foreign surveillance of foreign bad guys on foreign land. We need it! Get smart!
— Donald J. Trump (@realDonaldTrump) January 11, 2018
Trump’s tweet came after White House Press Secretary Sarah Sanders clarified the White House’s opposition to increased privacy protections Wednesday night, telling reporters the amendment “would re-establish the walls between intelligence and law enforcement that our country knocked down following the attacks of 9/11 in order to increase information sharing and improve our national security.”
The bill will now be taken up by the Senate, which, according to Paul, is less likely to introduce privacy protections before reauthorizing the program.
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Skweee has fast become a personal passion. It’s something I’ve tried to share with close friends and associates, but a lot of the time you get the same screwed up kind of expression made at you before that quick barrage of nervous laughter comes as the listener’s head cocks at that weird angle that means they’re trying to listen differently and understand what you’re playing them. At its heart though, skweee has a funk, a groove and yes, some of those squalling high pitched synthesizers that sound like the producers arms aren’t long enough to reach the lower octaves.
Born in Scandinavia to a select group of producers looking to release their own brand of synthetic funk, the sound has grown in breadth and style, but good skweee music always seems to retain a smirk and a sense of fun. It can be rooted as much in the drums or in the layers of hyper vibrant synthesizers but for me at least, there’s a perfect synergy between skweee and a smile. Plus the fact that a track like Eero Johannes’ ‘We Could Be Skweeeroes’ can sound like an on form funkafied Timbaland is often a resounding bonus.
Hiding on the tracklist of some of the scene’s defining compilations, the International Skweee and Museum of Future Sound series in particular, you’ll find the work of Henrik Von Euler, a Swede who’s productions have pushed boundaries of the primitive production techniques that the lo-fi style is renowned for. Having released music under an array of monikers, Rigas Den Andre stands proud as Von Euler’s out and out skweee alias. Over his debut album, Guilty Feet, No Rhythm he explored a netherworld of near broken bass tones, whilst he irked out his stuttered melodies over the top, producing classic tracks like ‘New Plastic Bastard,’ a track that tumbles into evolutions that contradict the ‘minimal’ and ‘primitive’ tags the music comes with.
With the vinyl release of his new album Speed Run imminent, we jumped at the chance to present a mix from Rigas, one of the most exciting and demented producers we’ve had the pleasure to come across. Whilst some skweee producers choose to get lost in the top end, conducting multiple channels of aural fluorescence, Von Euler harnesses the low end properly and he does so with vigour on new tracks like ‘December & Death’ and ‘Kid Rigarus;’ so it’s with great pleasure that we present Sonic Router’s 86th mix from Rigas Den Andre…
1. Elias Krantz – Tody MotMot (Rigas Remix)
2. 118Sthlm – På G
3. Rigas den Andre – Success Sucks Ass (feat. Spartan Lover)
4. Mother North – Butter Blues
5. Whodini – Haunted House Of Rock
6. Rigas den Andre – Aga Ago
7. Slow Hand Motem – Magik Grrrl
8. Limonious – 7 Synths
9. Easy & The Center Of Universe – Halloumi
10. Markis Sage – Kissing Cousins & Hustling
11. Daniel Savio – Sucky Salsiccia


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Minor testimonial inconsistencies in testimony about a trash pull did not mean there was no probable cause. United States v. Gershwin, 2018 U.S. Dist. LEXIS 77029 (E.D. Mich. May 8, 2018).
“Taken with Arguelles’s sex offender status, which included a prior conviction for possession of child pornography on an electronic device, as well as repeated violations of the sex offender registration requirements, it was fairly probable that the ‘underage’ folder on his cell phone contained pornographic material involving underage children.” United States v. Arguelles, 2018 U.S. Dist. LEXIS 77132 (N.D. Fla. May 8, 2018).

domain: law


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The phenomenal reception of the iPhone SE, soon-to-be-released iPhone 7, and supply-chain checks indicate Apple’s iPhone sales would rebound this year
When Apple Inc. (NASDAQ:AAPL) decided to roll out a new iPhone this year in the old, 4-inch form-factor, the company might not have imagined that it would soon run out of inventory. Orders for the iPhone SE are already facing shipment delays; this, combined with positive comments from Apple suppliers, suggests that the company is due for a rebound in iPhone sales.
Brian White, an analyst at Drexel Hamilton, currently maintains a Buy rating and $200 price target on the stock. The research firm held checks with Apple suppliers, which revealed that the company is on its way to experience a seasonal high in iPhone demand. According to the equity research firm, some of Apple’s Taiwanese suppliers have revealed that Apple’s iPhone sales for March were above-average compared to the last 11 months. Mr. White believes that sales will only get better for Apple this year, considering the imminent release of its iPhone 7 with the subsequent cycle driven even further from the company’s foray into new geographic territories.
According to Drexel Hamilton, in March, sales of “Apple Monitor” companies – Apple suppliers in Taiwan – rose 42% from the prior month, compared to the 11-month average of a 30% month-over-month increase. This spike portends well for Apple’s sales growth. It’s true that Apple’s first quarter of fiscal year 2016 was a disappointment as Drexel’s Apple Monitor reflected a 35% sequential decline in sales, which was pretty bad given that the average decline over the last decade has been only 17%.
Apple has guided for further decline in sales – a 30-35% sequential one – for the second quarter of the year. On the other hand, key Apple Taiwanese supplier Hon Hai has reported 21% growth for March, which bodes well for the iPhone maker, given that its sales pattern has been congruent to Apple’s sales growth pattern over the past 10 years.
To top this, analysts have pointed out the fact that the inventory of the newly-released iPhone SE is short of number of orders, as Apple struggles to keep up with a backlog of orders and has delayed shipment for several orders for over a fortnight. The iPhone SE’s success is evident by the fact that even though the model goes against the market trend of bigger-screen smartphones, with it, Apple has created a runway success from what was simply an upgrade to the iPhone 5S. In order to keep up with rising demand, the $606.5 billion company might have to keep churning out iPhone after iPhone.


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Author Class Level
Nicole has lived in South Florida her entire life and completed her undergrad at NSU, clearly, she loves change and yes, she still complains about the weather. Some of her passions include reading, writing, defending the Oxford comma, and critiquing unsatisfactory book-to-movie adaptations.
Chavannes, Nicole I.
"While I Am a Woman*,"
Digressions: Literary & Art Journal: Vol. 16, Article 22.
Available at: https://nsuworks.nova.edu/digressions/vol16/iss1/22


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What to Expect on a 60,000 Mile Tune-Up
It used to be that a car was an unnecessary luxury – long, long ago! Today, your car is a vital component to your life. As your primary means of transportation to work, school, grocery shopping and a myriad of other daily activities, it is essential that you maintain your vehicle. As you the miles add up, maintenance becomes even more important! In addition to regular oil changes, you must be certain to provide scheduled tune-ups, including a Everett 60,000 Mile Tune-Up.
What to Expect
Every manufacturer has it’s own specific requirements for scheduled maintenance, but there are a number of services to expect at your Everett 60,000 Mile Tune-Up:
- Timing Belt – will be inspected for excessive wear. Since a broken timing belt can lead to catastrophic (expensive) engine damage, it is essential that it be inspected and replaced as indicated. It is a good idea to replace the crankshaft and crankshaft seals at this time as well.
- Cooling System Hoses – a thorough inspection will be performed and hoses replaced as indicated.
- Spark Plugs – all will be replaced, regardless of type (platinum or non-platinum)
- Automatic Transmission Service – as with the 30K Tune-Up, the transmission fluid will be fully replaced. There is evidence that supports replacement, rather than pressure flushing as the safer course of action. To fully replace/clean the transmission fluid, your mechanic will open the plug, and completely drain the existing fluid. With the plug still out, new transmission fluid will be run through the system until it runs clear, after which, the plug is replaced and the system re-filled with new fluid.
- Cooling System Flush – similar to the ATF flush, the cooling system has an additional step; once the old coolant is drained from the cooling system, a detergent is flushed through the system, with the plug removed, until the solution runs clear. With the plug still out, new coolant is flushed through the system, until it runs free of detergent solution. The plug is replaced and the system re-filled with new coolant.
- Ignition Tune-Up – complete computer and emissions test is completed in addition to a thorough injection system service.
- Fluid Levels – all levels are checked and adjusted as indicated.
- Brake System – thorough inspection of the entire system, especially all brake pads and rotors/drums, repair/replace as necessary. Brake fluid lines are inspected for leaks and repaired/replaced as indicated.
- Suspension & Steering – full inspection and adjustments made as indicated
- Tires & Wheels – replacement of worn tires, rotation, balancing and pressure check, with adjustments as indicated.