Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial cell junctional adhesion molecule C plays a key role in the development of tumors in a murine model of ovarian cancer

Junctional adhesion molecule C (JAM‐C) is a transmembrane protein with significant roles in regulation of endothelial cell (EC) functions, including immune cell recruitment and angiogenesis. As these responses are important in promoting tumor growth, the role of EC JAM‐C in tumor development was investigated using the ID8 syngeneic model of ovarian cancer. Within 10–15 wk, intraperitoneally injected ID8 cells form multiple tumor deposits and ascites that resemble human high‐grade serous ovarian cancer. Compared to wild‐type mice, survival in this model was increased in EC JAM‐C knockouts (KOs; 88 vs. 96 d, P=0.04) and reduced in EC JAM‐C transgenics (88 vs. 78.5 d, P=0.03), mice deficient in or overexpressing EC JAM‐C, respectively. While tumor growth was significantly reduced in EC JAM‐C KOs (87% inhibition at 10 wk, P<0.0005), this was not associated with alterations in tumor vessel density or immune cell infiltration. However, tumor microvessels from EC JAM‐C‐deficient mice exhibited reduced pericyte coverage and increased vascular leakage, suggesting a role for EC JAM‐C in the development of functional tumor vessels. These findings provide evidence for a role for EC JAM‐C in tumor growth and aggressiveness as well as recruitment of pericytes to newly formed blood vessels in a model of ovarian cancer. —Leinster, D. A. , Colom, B. , Whiteford, J. R. , Ennis, D. P., Lockley, M. , McNeish, I. A. , Aurrand‐Lions, M. , Chavakis, T. , Imhof, B. A. , Balkwill, F. R. , Nourshargh, S. , Endothelial cell junctional adhesion molecule C plays a key role in the development of tumors in a murine model of ovarian cancer. FASEB J. 27, 4244–4253 (2013). www.fasebj. org
Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature

Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56–75% and 5–8% of the cases. To date, three KS patients with mosaic KMT2D deletions in blood lymphocytes have been described. We report on three additional subjects displaying KMT2D gene mosaics including one in which a single nucleotide change results in a new frameshift mutation (p.L1199HfsX7), and two with already-known nonsense mutations (p.R4484X and p.R5021X). Consistent with previously published cases, mosaic KMT2D mutations may result in mild KS facial dysmorphisms and clinical and neurobehavioral features, suggesting that these characteristics could represent the handles for genetic testing of individuals with slight KS-like traits.
Output feedback synthesis for sampled-data system with input saturation

In this paper we address the sampled-data regional and global H∞ synthesis problem for a class of linear plants subject to input saturation, where the sampling and hold rates are synchronous. Such a sampled-data system is expressed as a jump system, which is further described as a class of hybrid systems. Based on Lyapunov theorems for hybrid systems, a Lyapunov function is constructed and it is proved that the H∞ problem is equivalent to a purely discrete-time synthesis problem. The proposed synthesis approach is cast as a convex optimization over Linear Matrix Inequalities (LMIs), which leads to an output feedback controller with an internal deadzone loop, achieving stability and desired performance. The effectiveness of the proposed techniques is illustrated by one example consisting in a mechanical system with different sample-and-hold rates.
A review of risk perception measurement in tobacco control research

Objective To describe the characteristics of risk perception measures used in tobacco control research and to evaluate whether these measures incorporate measurement suggestions put forward by risk perception measurement scholars. Data sources Three databases (PubMed, PsycINFO and Web of Science) were searched in March 2015 for published English language peer-reviewed articles measuring tobacco risk perceptions (n=2557). The search string included terms related to tobacco products, perceptions and risk. Study selection Three coders independently coded abstracts for initial inclusion. In total, 441 articles met the initial inclusion criteria, and 100 were randomly selected for a full-text review. Data extraction A codebook was developed and tested through a training phase. Three coders independently coded the characteristics of each article (eg, population), multi-item measure (eg, validity) and item (eg, likelihood, affect, health outcome). Fifty-four articles, 33 measures and 239 items were coded. Data synthesis Twenty-one articles had a multi-item risk perception measure, and 12 articles had one risk perception item. Many of the items asked about general health outcomes (36%), did not specify the person for whom risk was being judged (44%; eg, self, average person) or did not specify the conditions of use (27%; eg, the product used, intensity of use). Conclusions There is little consistency across risk perception measures in tobacco research. There may be value in developing and disseminating best practices for assessing tobacco risk perceptions. A set of risk perception consensus measures may also benefit researchers in the field to help them consistently apply measurement recommendations.
An introduction to understanding elevation‐based topography: how elevation data are displayed – a review

The increased frequency of refractive surgery and the shift towards the correction of higher‐order aberrations necessitates a more detailed understanding of corneal shape. Early topography systems were based on Placido technology, as this was initially more intuitive for the general refractive surgeon. Newer computerized corneal modelling has increased our knowledge beyond what was previously possible. Elevation‐based systems utilize a direct triangulation technique to measure the corneal surface. Elevation‐based Scheimpflug imaging has advantages in that it allows for the measurement of both the anterior and posterior corneal surfaces. Posterior measurements are often the first indicators of future ectatic disease, in spite of completely normal anterior curvature. Examination of the posterior corneal surface can often reveal pathology that would otherwise be missed if one was relying on anterior analysis alone. Although there is little disagreement in diagnosing clinically evident keratoconus, agreement on what constitutes ‘form fruste’ or preclinical keratoconus remains elusive. The ability of elevation‐based topography to analyse both anterior and posterior corneal surfaces adds significantly to our ability to identify eyes believed to be ‘at risk’. As more knowledge is gained, it is appreciated that a full understanding of the workings of the human eye requires knowledge obtained from more than just one surface.
Dose–response to 3 months of quercetin-containing supplements on metabolite and quercetin conjugate profile in adults

Quercetin, a flavonol in fruits and vegetables, has been demonstrated to have antioxidant, anti-inflammatory and immunomodulating influences. The purpose of the present study was to determine if quercetin, vitamin C and niacin supplements (Q-500 = 500 mg/d of quercetin, 125 mg/d of vitamin C and 5 mg/d of niacin; Q-1000 = 1000 mg/d of quercetin, 250 mg/d of vitamin C and 10 mg/d of niacin) would alter small-molecule metabolite profiles and serum quercetin conjugate levels in adults. Healthy adults (fifty-eight women and forty-two men; aged 40–83 years) were assigned using a randomised double-blinded placebo-controlled trial to one of three supplement groups (Q-1000, Q-500 or placebo). Overnight fasted blood samples were collected at 0, 1 and 3 months. Quercetin conjugate concentrations were measured using ultra-performance liquid chromatography (UPLC)-MS/MS, and metabolite profiles were measured using two MS platforms (UPLC-quadrupole time-of-flight MS (TOFMS) and GC-TOFMS). Statistical procedures included partial least square discriminant analysis (PLS-DA) and linear mixed model analysis with repeated measures. After accounting for age, sex and BMI, quercetin supplementation was associated with significant shifts in 163 metabolites/quercetin conjugates (false discovery rate, P< 0·05). The top five metabolite shifts were an increase in serum guaiacol, 2-oxo-4-methylthiobutanoic acid, allocystathionine and two bile acids. Inflammatory and oxidative stress metabolites were not affected. PLS-DA revealed a clear separation only between the 1000 mg/d and placebo groups (Q2Y= 0·763). The quercetin conjugate, isorhamnetin-3-glucuronide, had the highest concentration at 3 months followed by quercetin-3-glucuronide, quercetin-3-sulphate and quercetin diglucuronide. In human subjects, long-term quercetin supplementation exerts disparate and wide-ranging metabolic effects and changes in quercetin conjugate concentrations. Metabolic shifts were apparent at the 1000 mg/d dose; further research is required to understand the health implications of these shifts.
Characterisation of Plasmodium invasive organelles; an ookinete microneme proteome

Secretion of microneme proteins is essential to Plasmodium invasion but the molecular composition of these secretory organelles remains poorly defined. Here, we describe the first Plasmodium microneme proteome. Purification of micronemes by subcellular fractionation from cultured ookinetes was confirmed by enrichment of known micronemal proteins and electron microscopy. Quantitation of electron micrographs showed >14‐fold microneme enrichment compared to the intact ookinete, such that micronemes comprised 85% of the identifiable organelles in the fraction. Gel LC‐MS/MS of the most abundant protein constituents of the fraction identified three known micronemal proteins chitinase, CTRP, SOAP, together with protein disulphide isomerase (PDI) and HSP70. Highly sensitive MudPIT shotgun proteomics described a total of 345 proteins in the fraction. M1 aminopeptidase and PDI, the former a recognised target of drug development, were both shown to have a micronemal location by IFA. We further identified numerous proteins with established vesicle trafficking and signaling functions consistent with micronemes being part of a regulated secretory pathway. Previously uncharacterised proteins comprise the largest functional group of the microneme proteome and will include secreted proteins important to invasion.
Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens

Significance A successful HIV-1 vaccine should generate an immune response capable of neutralizing the enormous diversity of globally circulating viruses. Here, we report the discovery and characterization of two clade C recombinant envelope glycoprotein trimers with native-like structural and antigenic properties, including epitopes for all known classes of broadly neutralizing antibodies (bnAbs). Together with previously described trimers from other clades, these two new trimers will aid in immunization strategies designed to induce bnAbs to HIV-1. A key challenge in the quest toward an HIV-1 vaccine is design of immunogens that can generate a broadly neutralizing antibody (bnAb) response against the enormous sequence diversity of the HIV-1 envelope glycoprotein (Env). We previously demonstrated that a recombinant, soluble, fully cleaved SOSIP.664 trimer based on the clade A BG505 sequence is a faithful antigenic and structural mimic of the native trimer in its prefusion conformation. Here, we sought clade C native-like trimers with comparable properties. We identified DU422 and ZM197M SOSIP.664 trimers as being appropriately thermostable (Tm of 63.4 °C and 62.7 °C, respectively) and predominantly native-like, as determined by negative-stain electron microscopy (EM). Size exclusion chromatography, ELISA, and surface plasmon resonance further showed that these trimers properly display epitopes for all of the major bnAb classes, including quaternary-dependent, trimer-apex (e.g., PGT145) and gp120/gp41 interface (e.g., PGT151) epitopes. A cryo-EM reconstruction of the ZM197M SOSIP.664 trimer complexed with VRC01 Fab against the CD4 binding site at subnanometer resolution revealed a striking overall similarity to its BG505 counterpart with expected local conformational differences in the gp120 V1, V2, and V4 loops. These stable clade C trimers contribute additional diversity to the pool of native-like Env immunogens as key components of strategies to induce bnAbs to HIV-1.
Police Discretion and Racial Disparity in Organized Retail Theft Arrests: Evidence from Texas

When definitions of two distinct criminal offenses overlap, power to decide which definition to apply to an arrest devolves to local law enforcement agencies. This discretion can lead to unequal treatment and denial of due process, especially when disadvantaged populations are arrested for nonviolent property crimes. We present a Bayesian analysis of arrests under a vaguely worded statutory scheme for retail theft in Texas, in which a shoplifter who is guilty of property theft is also guilty of organized retail theft. Using arrest data from the Texas Department of Public Safety, we find wide variation across law enforcement agencies in initial charging categories, with black and Hispanic arrestees being charged for the more serious crime more than white arrestees. The racial discrepancy is greater for agencies serving cities with higher per-capita income. These results highlight consequences of ambiguous provisions of criminal codes, and suggest a method for identifying agencies whose policies may have disparate impact across racial and ethnic groups.
Moral Destabilisation or Revivification: The Trend of Religion-Based Social Capital Following 9/11

Although different aspects of the 9/11 terrorist attacks have been widely studied, few researchers have attempted to understand both its religious and social aspects. In this context, considering the declining trend of social capital in the United States, whether 9/11 has become a window of opportunity for civic renewal and whether such renewal has been short-lived or long-lived become highly important to examine. To address these questions, this study examines whether the level of social capital in the American society changed from 2000 to 2006 and whether religious traditions had different effects on their members’ social capital levels following 9/11.
Contrasting responses of functional diversity to major losses in taxonomic diversity

Significance Global biodiversity consists not only of the sum of taxonomic units such as species, but also of their ecological or functional variety. These two components of biodiversity might be expected to rise or fall in tandem, but we find they are capable of strikingly independent behavior. In three major declines in taxonomic diversity—spatially from equator to poles today and temporally in the Permian–Triassic and Cretaceous–Paleogene extinctions—only the first one shows a concomitant drop in the number of functional groups, whereas virtually all functional categories survived the extinction events. We present a conceptual framework for understanding this contrast, and we suggest that the differing behavior of these two biodiversity components will be important in anticipating the impacts of impending losses in today’s biota. Taxonomic diversity of benthic marine invertebrate shelf species declines at present by nearly an order of magnitude from the tropics to the poles in each hemisphere along the latitudinal diversity gradient (LDG), most steeply along the western Pacific where shallow-sea diversity is at its tropical maximum. In the Bivalvia, a model system for macroevolution and macroecology, this taxonomic trend is accompanied by a decline in the number of functional groups and an increase in the evenness of taxa distributed among those groups, with maximum functional evenness (FE) in polar waters of both hemispheres. In contrast, analyses of this model system across the two era-defining events of the Phanerozoic, the Permian–Triassic and Cretaceous–Paleogene mass extinctions, show only minor declines in functional richness despite high extinction intensities, resulting in a rise in FE owing to the persistence of functional groups. We hypothesize that the spatial decline of taxonomic diversity and increase in FE along the present-day LDG primarily reflect diversity-dependent factors, whereas retention of almost all functional groups through the two mass extinctions suggests the operation of diversity-independent factors. Comparative analyses of different aspects of biodiversity thus reveal strongly contrasting biological consequences of similarly severe declines in taxonomic diversity and can help predict the consequences for functional diversity among different drivers of past, present, and future biodiversity loss.
Cognitive and vision loss affects the topography of the attentional visual field.

PURPOSE The attentional visual field (AVF), which describes a person's ability to divide attention and extract visual information from the visual field (VF) within a glance, has been shown to be a good predictor of driving performance. Despite this, very little is known about the shape of the AVF and the factors that affect it. The purposes of this study were to describe the AVF in a large sample of older drivers and identify demographic, cognitive, and vision factors associated with AVF performance and shape. METHODS Registered drivers between 67 and 87 years of age, residing in Greater Salisbury, Maryland, were recruited to participate in the study. Participants underwent a battery of visual and cognitive assessments and completed various questionnaires for demographics, medical history, and history of depression. The AVF was assessed using a divided-attention protocol within the central 20 degrees radius along the four principal meridians. The shape of the AVF was classified as either symmetric or one of two asymmetric shape profiles. RESULTS Symmetrically shaped AVFs were found in just 34% of participants. AVF performance was significantly better along the horizontal (15.3 degrees ) than the vertical (11.3 degrees ) meridian (P < 0.05). After adjusting for AVF area, we found that poorer cognitive and vision performance was associated with a symmetric AVF shape. Overall AVF extent was predicted by vision and cognitive measures as well as various demographic factors. CONCLUSIONS Good vision and cognitive ability appear to be associated with having an asymmetric as opposed to a symmetric AVF shape profile.
Fracture prevention by femoroplasty—cement augmentation of the proximal femur

The prevention of hip fractures is a desirable goal to reduce morbidity, mortality, and socio‐economic burden. We evaluated the influence on femoral strength of different clinically applicable cementing techniques as “femoroplasty. ” Twenty‐eight human cadaveric femora were augmented by means of four clinically applicable percutaneous cementing techniques and then tested biomechanically against their native contralateral control to determine fracture strength in an established biomechanical model mimicking a fall on the greater trochanter. The energy applied until fracture could be significantly increased by two of the methods by 160% (53.1 Nm vs. 20.4 Nm, p < 0.001) and 164% (47.1 Nm vs. 17.8 Nm, p = 0.008), respectively. The peak load to failure was significantly increased by three of the methods by 23% (3818.3 N vs. 3095.7 N, p = 0.003), 35% (3698.4 N vs. 2737.5 N, p = 0.007), and 12% (3056.8 N vs. 2742.8 N, p = 0.005), respectively. The femora augmented with cemented double drill holes had a lower fracture strength than the single drilled ones. Experimental femoroplasty is a technically feasible procedure for the prophylactic reinforcement of the osteoporotic proximal femur and, hence, could be an auxiliary treatment option to protect the proximal femur against osteoporotic fractures. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1753–1758, 2011
Abolishment of corporal punishment in Zambia: Evaluation alternative modes of discipline in selected Government Secondary Schools in Lusaka District

The study aimed at evaluating alternative modes of discipline educators use to instil discipline in pupils after the abolishment of corporal punishment in 2003 in Zambian schools. The objectives of this study were: to verify the alternative modes of discipline to corporal punishment educators use to instil discipline in pupils in Government Secondary Schools; ascertain their suitability; explore challenges educators encounter in using the alternative modes to instil pupils‟ discipline, and; solicit proposals to mitigate the challenges. The study implored qualitative approach and a descriptive survey design. Data was collected from the documents reviewed; and through individual interviews, focus group discussions from a sample of 51 participants which comprised 21 teachers, 21 pupils, 3 school administrators, 3 Parent Teachers Association (PTA) representatives, from three Government Secondary Schools, and 3 policy-makers from the Ministry of General Education (MoGE) and Human Rights Commission (HRC) offices. Purposive sampling was used to sample policy makers, school administrators and PTA representatives. Typical and homogeneous sampling was used to sample teachers and pupils. Data was analysed according to emerging themes, and presented on tables and graphs. The findings were that educators use dialogue, suspension, counselling, and manual to instil discipline in pupils. With regards to suitability, the findings were that alternative modes are suitable to use on pupils discipline as they are non-corporal, create a sense of responsibility in pupils, instil discipline and are lawful. The established challenges were that the modes consume time, are not effective to instil discipline, non-compliance by parents and pupils, lack of knowledge by teachers and pupils. The findings on mitigation of challenges were: the MoGE to prescribe alternative modes as a guide for educators and provide them with knowledge and skills to enhance the administration of discipline, teamwork by parents and teachers and insisting on pupils to adhere on school rules. In light of the findings, the study recommended that schools should have guidance and counselling departments with qualified counsellors to help in pupil discipline, educators to explore better contemporary trends on positive discipline, all schools to establish and strengthen child rights clubs and train peer educators on the importance of good discipline. Finally, more research to be conducted on ways of improving discipline in Government Secondary Schools.