bluuebunny/crossref_metadata_2025_split huggingface dataset:
Processing of stimulus content but not of emotional valence is altered in persons with Williams syndrome
Authors: Key A. P. , Dykens E. M. 
Published: July 2016

AbstractBackgroundIndividuals with Williams syndrome (WS) exhibit hypersociability and may respond atypically to emotional information in social and nonsocial stimuli. It is not yet clear whether these difficulties are specific to emotional content or stimulus type. This study examined the neural processes supporting social and emotional information processing in WS.MethodVisual event‐related potentials were recorded in 19 adults with WS and 10 typical peers during a picture‐viewing task requiring detection of smiling faces among other social and nonsocial images with positive and negative emotional content.ResultsThe participant groups were not significantly different in affective processing of positive and negative stimuli and perceived faces as different from nonsocial images. Participants with WS showed subtle differences in face‐specific perceptual processes (e.g. face inversion, N170 lateralisation), suggesting a more feature‐based processing. They also demonstrated reduced attention and arousal modulation (P3, late positive potential) in response to faces vs. nonsocial images. These differences were independent of intelligence quotient.ConclusionsThere was no evidence of greater than typical perceptual, attentional or affective processing of social information in WS. The results support the idea that altered face perception processes and not the increased salience of social stimuli or difficulties with emotion discrimination may contribute to the hypersocial phenotype in WS.
Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood–brain barrier
Authors: Thomsen Maj Schneider , Birkelund Svend , Burkhart Annette , Stensballe Allan , Moos Torben 
Published: July 2016

AbstractThe brain vascular basement membrane is important for both blood–brain barrier (BBB) development, stability, and barrier integrity and the contribution hereto from brain capillary endothelial cells (BCECs), pericytes, and astrocytes of the BBB is probably significant. The aim of this study was to analyse four different in vitro models of the murine BBB for expression and possible secretion of major basement membrane proteins from murine BCECs (mBCECs). mBCECs, pericytes and glial cells (mainly astrocytes and microglia) were prepared from brains of C57BL/6 mice. The mBCECs were grown as monoculture, in co‐culture with pericytes or mixed glial cells, or as a triple‐culture with both pericytes and mixed glial cells. The integrity of the BBB models was validated by measures of transendothelial electrical resistance (TEER) and passive permeability to mannitol. The expression of basement membrane proteins was analysed using RT‐qPCR, mass spectrometry and immunocytochemistry. Co‐culturing mBCECs with pericytes, mixed glial cells, or both significantly increased the TEER compared to the monoculture, and a low passive permeability was correlated with high TEER. The mBCECs expressed all major basement membrane proteins such as laminin‐411, laminin‐511, collagen [α1(IV)]2α2(IV), agrin, perlecan, and nidogen 1 and 2 in vitro. Increased expression of the laminin α5 subunit correlated with the addition of BBB‐inducing factors (hydrocortisone, Ro 20‐1724, and pCPT‐cAMP), whereas increased expression of collagen IV α1 primarily correlated with increased levels of cAMP. In conclusion, BCECs cultured in vitro coherently form a BBB and express basement membrane proteins as a feature of maturation.
imageCover Image for this issue: doi: 10.1111/jnc.13789.
An Incentive‐Compatible Experiment on Probabilistic Insurance and Implications for an Insurer's Solvency Level
Authors: Zimmer Anja , Gründl Helmut , Schade Christian D. , Glenzer Franca 
Published: July 2016

ABSTRACTThis article is the first to conduct an incentive‐compatible experiment using real monetary payoffs to test the hypothesis of probabilistic insurance, which states that willingness to pay for insurance decreases sharply in the presence of even small default probabilities as compared to a risk‐free insurance contract. In our experiment, 181 participants state their willingness to pay for insurance contracts with different levels of default risk. We find that the willingness to pay sharply decreases with increasing default risk. Our results, hence, strongly support the hypothesis of probabilistic insurance. Furthermore, we study the impact of customer reaction to default risk on an insurer's optimal solvency level using our experimentally obtained data on insurance demand. We show that an insurer should choose to be default‐free rather than having even a very small default probability. This risk strategy is also optimal when assuming substantial transaction costs for risk management activities undertaken to achieve the maximum solvency level.
God and Dispositional Essentialism: An Account of the Laws of Nature
Authors: Adams Dani 
Published: July 2016

AbstractIt is common to appeal to governing laws of nature in order to explain the existence of natural regularities. Classical theism, however, maintains the sovereignty thesis: everything distinct from God is created by him and is under his guidance and control. It follows from this that God must somehow be responsible for natural laws and regularities. Therefore, theists need an account of the relation between (i) regularities, (ii) laws, and (iii) God. I examine competing accounts of laws of nature and conclude that dispositional essentialism provides the most satisfactory explanation of the relation between (i), (ii) and (iii).
Viral load and ganciclovir (GCV) concentration in cerebrospinal fluid of patients successfully treated with GCV or valGCV for human herpesvirus 6 encephalitis/myelitis following umbilical cord blood transplantation
Authors: Morita D. , Hirabayashi K. , Katsuyama Y. , Morokawa H. , Motobayashi M. , Kurata T. , Shigemura T. , Tanaka M. , Inaba Y. , Koike K. , Nakazawa Y. 
Published: July 2016

AbstractWe describe successful treatment of 3 cases of human herpesvirus 6 (HHV‐6) encephalitis/myelitis following cord blood transplantation (CBT). Ganciclovir (GCV) (10 mg/kg/day) reduced HHV‐6 load to undetectable levels in cerebrospinal fluid (CSF). Early dose reduction in the presence of HHV‐6 detectable in CSF resulted in an increased HHV‐6 load. GCV was capably shifted to valganciclovir (VGCV) with an almost equivalent concentration. GCV/VGCV may be effective for HHV‐6 encephalitis/myelitis after CBT, although HHV‐6 load in CSF should be monitored.
Coordination of I&C Design With the Obligatory Consideration of Human Factors: A Project Management Approach
Authors: Sanz Silvia , Ciriello Antonio , Krause Wolfgang , Eisinger Asriel 
Published: July 2016

Human factors engineering (HFE), such as other engineering disciplines involved in plant design, cannot be considered retroactively. The engineering principles and methods derived from deep knowledge of the cognitive and perceptual capabilities and limitations of the plant’s “human element” are applied instead throughout the plant design. Focusing HFE efforts, the plant’s HMI is designed to ensure effective and error-free performance of the monitoring, control, and administrative tasks allocated to the control-room crew. A project’s HFE program prescribes three main steps (1) The task analysis and the analyses of plant monitoring and control functions to identify those to be performed manually (all others are performed automatically, or in a combination of manual and automatic, while still manually monitored) and determine in turn the HMI inventory of information displays, controls, alarms, and operating procedures required to support their performance. (2) The guided design of the plant’s HMI, ensuring its compliance with HFE principles and the completeness and correctness of the task support it provides. (3) The subsequent evaluation of operator performance, trained to follow the operating procedures and use of the HMI. Authors’ experience shows that the three following required steps pose challenges to project execution: (1) the acquisition and analysis of the multidisciplinary functional requirements (related to plant monitoring and control); (2) the likely interdisciplinary analysis and how fulfillment of these requirements shall be allocated to I&C automation systems or operators (or both); and (3) the HFE-guided HMI design and validation. An additional fourth challenge poses a timely and cost-effective application of HFE to I&C engineering, which can be achieved by adequate planning and project management procedures. This paper aims to summarize some of our industrial experiences gained in new builds and modernization projects of nuclear power plants around the world.
Cognitive Disequilibrium and Service-Learning in Physical Education Teacher Education: Perceptions of Pre-Service Teachers in a Study Abroad Experience
Authors: Ward Stefan , Pellett Heidi Henschel , Perez Mark I. 
Published: July 2016

Purpose:The purpose of this study was to explore preservice teachers’ experiences of cognitive disequilibrium (CD) theory during a service-learning project in a study abroad experience.Method:A case study with 8 participants was used. Data sources consisted of: Formal interviews, videos of planning, videos of teaching, videos of reflection sessions, and informal interviews. Data were analyzed utilizing open and axial coding (Corbin & Strauss, 2008). Trustworthiness strategies included: prolonged engagement, multiple data source triangulation, and member checks.Results:Results indicated four themes: “We made it our own thing”, “Summer camp for teachers”, “Struggle and disequilibrium”, and “By the end it was a transformation”.Discussion/Conclusions:CD was ultimately positive for these students. The positive resolution of CD catalyzed a transformative effect on their perceptions of their teaching. This was supported by positive peer interaction.
Delamanid Coadministered with Antiretroviral Drugs or Antituberculosis Drugs Shows No Clinically Relevant Drug-Drug Interactions in Healthy Subjects
Authors: Mallikaarjun Suresh , Wells Charles , Petersen Carolyn , Paccaly Anne , Shoaf Susan E. , Patil Shiva , Geiter Lawrence 
Published: July 2016

ABSTRACT

Delamanid is a medicinal product approved for treatment of multidrug-resistant tuberculosis. Three studies were conducted to evaluate the potential drug-drug interactions between delamanid and antiretroviral drugs, including ritonavir, a strong inhibitor of CYP3A4, and selected anti-TB drugs, including rifampin, a strong inducer of cytochrome P450 (CYP) isozymes. Multiple-dose studies were conducted in parallel groups of healthy subjects. Plasma samples were analyzed for delamanid, delamanid metabolite, and coadministered drug concentrations, and pharmacokinetic (PK) parameters were determined. The magnitude of the interaction was assessed by the ratio of the geometric means and 90% confidence intervals. Coadministration of delamanid with tenofovir or efavirenz did not affect the PK characteristics of delamanid. Coadministration of Kaletra (lopinavir/ritonavir) with delamanid resulted in an approximately 25% higher delamanid area under the concentration-time curve from time 0 to the end of the dosing interval (AUCτ). Tenofovir, efavirenz, lopinavir, and ritonavir exposure were not affected by delamanid. Coadministration of delamanid with the TB drugs (ethambutol plus Rifater [rifampin, pyrazinamide, and isoniazid]) resulted in lower delamanid exposures (47 and 42% for the AUCτ and C
max
[maximum concentration of a drug in plasma] values, respectively), as well as decreased exposure of three primary metabolites (approximately 30 to 50% lower AUCτ values). Delamanid did not affect rifampin, pyrazinamide, and isoniazid exposure; the ethambutol AUCτ and
C
max
values were about 25% higher with delamanid coadministration. The lack of clinically significant drug-drug interactions between delamanid and selected antiretroviral agents (including the strong CYP inhibitor ritonavir) and a combination of anti-TB drugs was demonstrated. Although there was a decrease in the delamanid concentrations when coadministered with ethambutol plus Rifater, this is likely related to decreased delamanid absorption and not to CYP induction.
First Report of German Cockroaches (Blattella germanica) as Reservoirs of CTX-M-15 Extended-Spectrum-β-Lactamase- and OXA-48 Carbapenemase-Producing Enterobacteriaceae in Batna University Hospital, Algeria
Authors: Loucif Lotfi , Gacemi-Kirane Djamila , Cherak Zineb , Chamlal Naima , Grainat Nadia , Rolain Jean-Marc 
Published: July 2016

ABSTRACT

Here we report the isolation of extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing
Enterobacteriaceae
from German cockroaches caught in the burn unit of Batna University Hospital in Algeria. Nine of 12 isolates harbored the
bla
CTX-M-15
ESBL gene. One
Enterobacter cloacae
isolate belonging to sequence type 528 coexpressed the
bla
OXA-48
,
bla
CTX-M-15
, and
bla
TEM
genes. Our findings indicate that cockroaches may be one of the most dangerous reservoirs for ESBL and carbapenemase producers in hospitals.
Characterization of Spectinomycin Resistance in Streptococcus suis Leads to Two Novel Insights into Drug Resistance Formation and Dissemination Mechanism
Authors: Huang Kaisong , Zhang Qiang , Song Yajing , Zhang Zhewen , Zhang Anding , Xiao Jingfa , Jin Meilin 
Published: July 2016

ABSTRACT

Spectinomycin is an aminocyclitol antibiotic used clinically to treat a variety of infections in animals. Here, we characterized drug resistance prevalence in clinical
Streptococcus suis
isolates and discovered a novel resistance mechanism in which the s5 mutation (Gly26Asp) results in high spectinomycin resistance. Additionally, a novel integrative and conjugative element encompassing a multidrug resistance
spw_like-aadE-lnu
(B)-
lsa
(E) cluster and a cadmium resistance operon were identified, suggesting a possible cause for the wide dissemination of spectinomycin resistance in
S. suis
.
Saliva-Induced Clotting Captures Streptococci: Novel Roles for Coagulation and Fibrinolysis in Host Defense and Immune Evasion
Authors: Wollein Waldetoft Kristofer , Mohanty Tirthankar , Karlsson Christofer , Mörgelin Matthias , Frick Inga-Maria , Malmström Johan , Björck Lars 
Published: July 2016

ABSTRACTStreptococcal pharyngitis is among the most common bacterial infections, but the molecular mechanisms involved remain poorly understood. Here we investigate the interactions among three major players in streptococcal pharyngitis: streptococci, plasma, and saliva. We find that saliva activates the plasma coagulation system through both the extrinsic and the intrinsic pathways, entrapping the bacteria in fibrin clots. The bacteria escape the clots by activating host plasminogen. Our results identify a potential function for the intrinsic pathway of coagulation in host defense and a corresponding role for fibrinolysis in streptococcal immune evasion.
Recombinant Mucin-Type Fusion Proteins with a Galα1,3Gal Substitution as Clostridium difficile Toxin A Inhibitors
Authors: Cherian Reeja Maria , Jin Chunsheng , Liu Jining , Karlsson Niclas G. , Holgersson Jan 
Published: July 2016

ABSTRACT

The capability of a recombinant mucin-like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL-1/mIgG2b), carrying Galα1,3Galβ1,4GlcNAc determinants to bind and inhibit
Clostridium difficile
toxin A (TcdA) was investigated. The fusion protein, produced by a glyco-engineered stable CHO-K1 cell line and designated C-PGC2, was purified by affinity and gel filtration chromatography from large-scale cultures. Liquid chromatography-mass spectrometry was used to characterize
O
-glycans released by reductive β-elimination, and new diagnostic ions to distinguish Galα1,3Gal- from Galα1,4Gal-terminated
O
-glycans were identified. The C-PGC2 cell line, which was 20-fold more sensitive to TcdA than the wild-type CHO-K1, is proposed as a novel cell-based model for TcdA cytotoxicity and neutralization assays. The C-PGC2-produced fusion protein could competitively inhibit TcdA binding to rabbit erythrocytes, making it a high-efficiency inhibitor of the hemagglutination property of TcdA. The fusion protein also exhibited a moderate capability for neutralization of TcdA cytotoxicity in both C-PGC2 and CHO-K1 cells, the former with and the latter without cell surface Galα1,3Galβ1,4GlcNAc sequences. Future studies in animal models of
C. difficile
infection will reveal its TcdA-inhibitory effect and therapeutic potential in
C. difficile
-associated diseases.
Mutagen Synergy: Hypermutability Generated by Specific Pairs of Base Analogs
Authors: Ang Jocelyn , Song Lisa Yun , D'Souza Sara , Hong Irene L. , Luhar Rohan , Yung Madeline , Miller Jeffrey H. 
Published: July 2016

ABSTRACT

We tested pairwise combinations of classical base analog mutagens in
Escherichia coli
to study possible mutagen synergies. We examined the cytidine analogs zebularine (ZEB) and 5-azacytidine (5AZ), the adenine analog 2-aminopurine (2AP), and the uridine/thymidine analog 5-bromodeoxyuridine (5BrdU). We detected a striking synergy with the 2AP plus ZEB combination, resulting in hypermutability, a 35-fold increase in mutation frequency (to 53,000 × 10
−8
) in the
rpoB
gene over that with either mutagen alone. A weak synergy was also detected with 2AP plus 5AZ and with 5BrdU plus ZEB. The pairing of 2AP and 5BrdU resulted in suppression, lowering the mutation frequency of 5BrdU alone by 6.5-fold. Sequencing the mutations from the 2AP plus ZEB combination showed the predominance of two new hot spots for A·T→G·C transitions that are not well represented in either single mutagen spectrum, and one of which is not found even in the spectrum of a mismatch repair-deficient strain. The strong synergy between 2AP and ZEB could be explained by changes in the dinucleoside triphosphate (dNTP) pools.

IMPORTANCE
Although mutagens have been widely studied, the mutagenic effects of combinations of mutagens have not been fully researched. Here, we show that certain pairwise combinations of base analog mutagens display synergy or suppression. In particular, the combination of 2-aminopurine and zebularine, analogs of adenine and cytidine, respectively, shows a 35-fold increased mutation frequency compared with that of either mutagen alone. Understanding the mechanism of synergy can lead to increased understanding of mutagenic processes. As combinations of base analogs are used in certain chemotherapy regimens, including those involving ZEB and 5AZ, these results indicate that testing the mutagenicity of all drug combinations is prudent.
Perils of police action: a cautionary tale from US data sets
Authors: Miller Ted R , Lawrence Bruce A , Carlson Nancy N , Hendrie Delia , Randall Sean , Rockett Ian R H , Spicer Rebecca S 
Published: July 2016

ObjectiveTo count and characterise injuries resulting from legal intervention by US law enforcement personnel and injury ratios per 10 000 arrests or police stops, thus expanding discussion of excessive force by police beyond fatalities.DesignEcological.PopulationThose injured during US legal police intervention as recorded in 2012 Vital Statistics mortality census, 2012 Healthcare Cost and Utilization Project nationwide inpatient and emergency department samples, and two 2015 newspaper censuses of deaths.Exposure2012 and 2014 arrests from Federal Bureau of Investigation data adjusted for non-reporting jurisdictions; street stops and traffic stops that involved vehicle or occupant searches, without arrest, from the 2011 Police Public Contact Survey (PPCS), with the percentage breakdown by race computed from pooled 2005, 2008 and 2011 PPCS surveys due to small case counts.ResultsUS police killed or injured an estimated 55 400 people in 2012 (95% CI 47 050 to 63 740 for cases coded as police involved). Blacks, Native Americans and Hispanics had higher stop/arrest rates per 10 000 population than white non-Hispanics and Asians. On average, an estimated 1 in 291 stops/arrests resulted in hospital-treated injury or death of a suspect or bystander. Ratios of admitted and fatal injury due to legal police intervention per 10 000 stops/arrests did not differ significantly between racial/ethnic groups. Ratios rose with age, and were higher for men than women.ConclusionsHealthcare administrative data sets can inform public debate about injuries resulting from legal police intervention. Excess per capita death rates among blacks and youth at police hands are reflections of excess exposure. International Classification of Diseases legal intervention coding needs revision.
Abstract 1002: IDH1 promotes tumor growth and resistance to targeted therapies in the absence of mutation
Authors: Stegh Alexander H. 
Published: July 2016

Abstract
Metabolic abnormalities of cancers provide opportunities for novel tumor-specific therapies. Isocitrate dehydrogenases (IDHs) are enzymes of the tricarboxylic acid (TCA) cycle that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) and the reduction of NADP+ to NADPH. Oncogenic mutations in two IDH-encoding genes (IDH1 and IDH2) have been identified in acute myelogenous leukemia, low-grade glioma, and secondary glioblastoma (GBM). Our in silico analysis of The Cancer Genome Atlas (TCGA) data combined with wet-bench analysis of tumor extracts indicate that non-mutated IDH1 mRNA and protein is commonly overexpressed in primary GBM. We show that genetic and pharmacologic inactivation of IDH1 decreases GBM cell growth, promotes a more differentiated tumor cell state, increases apoptosis in response to targeted therapies, and prolongs survival of animal subjects bearing patient-derived xenografts (PDXs). On molecular levels, diminished IDH1 activity results in reduced α-KG and NADPH production, which is paralleled by deficient metabolic flux from glucose or acetate into lipids, exhaustion of reduced glutathione, increased levels of reactive oxygen species (ROS), and enhanced histone methylation and differentiation marker expression. These findings suggest that IDH1 upregulation represents a common mechanism of metabolic adaptation of GBM to support macromolecular synthesis, aggressive growth, and therapy resistance.
Citation Format: Alexander H. Stegh. IDH1 promotes tumor growth and resistance to targeted therapies in the absence of mutation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1002.