Miracle-dz/UniFAR-FTUs huggingface dataset:
High Affinity Neurexin Binding to Cell Adhesion G-protein-coupled Receptor CIRL1/Latrophilin-1 Produces an Intercellular Adhesion Complex

Background: Neurexins and CIRL/latrophilin-1 (CL1) are independent synaptic receptors for α-latrotoxin. Results: Neurexins and CL1 form a high affinity complex that mediates intercellular adhesion and is regulated by neurexin alternative splicing. Conclusion: Thus, two independent α-latrotoxin receptors interact trans-cellularly to form a connection between neurons. Significance: The neurexin-CL1 complex may be involved in trans-synaptic cell adhesion and mediate α-latrotoxin toxicity. The G-protein-coupled receptor CIRL1/latrophilin-1 (CL1) and the type-1 membrane proteins neurexins represent distinct neuronal cell adhesion molecules that exhibit no similarities except for one common function: both proteins are receptors for α-latrotoxin, a component of black widow spider venom that induces massive neurotransmitter release at synapses. Unexpectedly, we have now identified a direct binding interaction between the extracellular domains of CL1 and neurexins that is regulated by alternative splicing of neurexins at splice site 4 (SS4). Using saturation binding assays, we showed that neurexins lacking an insert at SS4 bind to CL1 with nanomolar affinity, whereas neurexins containing an insert at SS4 are unable to bind. CL1 competed for neurexin binding with neuroligin-1, a well characterized neurexin ligand. The extracellular sequences of CL1 contain five domains (lectin, olfactomedin-like, serine/threonine-rich, hormone-binding, and G-protein-coupled receptor autoproteolysis-inducing (GAIN) domains). Of these domains, the olfactomedin-like domain mediates neurexin binding as shown by deletion mapping. Cell adhesion assays using cells expressing neurexins and CL1 revealed that their interaction produces a stable intercellular adhesion complex, indicating that their interaction can be trans-cellular. Thus, our data suggest that CL1 constitutes a novel ligand for neurexins that may be localized postsynaptically based on its well characterized interaction with intracellular SH3 and multiple ankyrin repeats adaptor proteins (SHANK) and could form a trans-synaptic complex with presynaptic neurexins.
Epoxy‐boehmite nanocomposites as new insulating materials

The results of a comparative analysis performed on specimens of nanostructured epoxy resins obtained by different boehmite filler concentrations are reported in this paper. The specimens were prepared by dispersion of boehmite nanoparticles into a cycloaliphatic epoxy resin cross linked under UV. Photopolymerization process was followed by RT-FTIR and the properties of uv-cured films investigated. Dielectric properties, in particular space charge accumulation, are measured as a function of nanofiller content. Results indicate that space charge build up and charge mobility are affected largely by filler content. Concentrations of nanofiller of 5–7 wt % show significant decrease of the space charge with respect to the base-epoxy resin and an increased mobility of negative carriers. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Role of Protein Phosphatase 2A in mGluR5-regulated MEK/ERK Phosphorylation in Neurons*

The regulation of protein phosphorylation requires coordinated interaction between protein kinases and protein phosphatases (PPs). Recent evidence has shown that the Gαq-protein-coupled metabotropic glutamate receptor (mGluR) 5 up-regulates phosphorylation of MAPK/ERK1/2. However, signaling mechanisms linking mGluR5 to ERK are poorly understood. In this study, roles of a major serine/threonine PP, PP2A, in this event were evaluated in cultured neurons. We found that the PP1/2A inhibitors okadaic acid and calyculin A mimicked the effect of the mGluR5 agonists (RS)-3,5-dihydroxyphenylglycine and (RS)-2-chloro-5-hydroxyphenylglycine in facilitating phosphorylation of ERK1/2 and its upstream kinase, MEK1/2, in a PP2A-dependent but not PP1-dependent manner. Co-administration of either inhibitor with an mGluR5 agonist produced additive phosphorylation of ERK1/2. Enzymatic assays showed a basal level of phosphatase activity of PP2A under normal conditions, and activation of mGluR5 selectively inhibited PP2A, but not PP1, activity. In addition, a physical association of the cytoplasmic C terminus of mGluR5 with PP2A was observed, and ligand activation of mGluR5 reduced mGluR5-PP2A binding. Additional mechanistic studies revealed that mGluR5 activation increased tyrosine (Tyr307) phosphorylation of PP2A, which was dependent on activation of a p60c-Src family tyrosine kinase, but not the epidermal growth factor receptor tyrosine kinase and resulted in dissociation of PP2A from mGluR5 and reduced PP2A activity. Together, we have identified a novel, mGluR5-triggered signaling mechanism involving use- and Src-dependent inactivation of PP2A, which contributes to mGluR5 activation of MEK1/2 and ERK1/2.
Medial Tibial Reduction Osteotomy is Associated with Excellent Outcomes and Improved Coronal Alignment

Background: The medial tibial reduction osteotomy (MTRO) was introduced to achieve coronal ligamentous balance in total knee arthroplasty (TKA) patients with substantial preoperative varus deformity. Limited data exists on the outcomes of patients requiring an MTRO. This study compares outcomes of a matched cohort of patients that either required or did not require an MTRO during TKA. Methods: A retrospective review was performed on 67 patients that underwent an MTRO during primary TKA to achieve coronal balance. This patient population was matched 1:1 to another cohort of TKA patients by age, gender, and BMI that did not require an MTRO. A clinical and radiographic evaluation was utilized to compare the two cohorts. Results: Preoperatively, the tibiofemoral angle was 3.42° valgus versus 6.12° varus in the control and MTRO cohorts respectively (p=0.01). Mean postoperative tibiofemoral angles were 3.40° versus 2.43° valgus respectively. Postoperative Knee Society Scores were superior in the MTRO cohort (183.84 versus 174.58; p=0.04). Intraoperatively, no superficial MCL releases were required to achieve coronal balance in either cohort. Complications were similar and limited in both groups. Medial tibial bone resorption was observed in 64% of MTRO subjects averaging 2.02mm versus only 0.3mm in the control cohort ( p=0.01). Conclusion: Patients requiring an MTRO achieved similar alignment and superior knee scores compared to a control cohort with less varus deformity. This procedure eliminated the need for release of the superficial MCL. Resorption of medial tibial bone was commonly observed, possibly secondary to saw-induced thermal necrosis associated with performing an MTRO.
Gut Hormones and ‘Minimal Enteral Feeding’

ABSTRACT. Previously we have identified multiple surges in plasma concentrations of gut hormones post‐natally in enterally fed term and preterm infants. In this study on 104 preterm infants we have shown that such surges are induced after ingestion of very small quantities of human milk. Whereas 6‐day‐old exclusively parenterally fed infants showed no postnatal elevation in enteroglucagon, gastrin, GIP, motilin and neurotensin, infants recovering from hyaline membrane disease who had received restricted enteral nutrition had similar hormone surges to those seen in well infants on full enteral feeds. Significant elevations in enteroglucagon, gastrin and GIP occurred after a cumulative mean enteral feed volume since birth of only 24 ml (12 ml/kg body weight) had been consumed and after a mean total intake of 96 ml (50 ml/kg) the response was maximal. Greater feed volumes were required to produce a neurotensin or motilin surge, but even these volumes were substantially lower than those required for full enteral feeding. In view of the proposed roles of gut hormones in the adaptation to extrauterine nutrition these data have implications for mammalian biology and raise the possibility that ‘minimal enteral feeding’ might have a clinical therapeutic role in infants undergoing prolonged parenteral nutrition.
Neuroimaging findings in disruptive behavior disorders

Decades of research have shown that youths with disruptive behavior disorders (DBD) are a heterogeneous population. Over the past 20 years, researchers have distinguished youths with DBD as those displaying high (DBD/HCU) versus low (DBD/LCU) callous-unemotional (CU) traits. These traits include flat affect and reduced empathy and remorse, and are associated with more severe, varied, and persistent patterns of antisocial behavior and aggression. Conduct problems in youths with HCU and LCU are thought to reflect distinct causal vulnerabilities, with antisocial behavior in youths with DBD/HCU reflecting a predominantly genetic etiology, while antisocial behavior in youths with DBD/LCU is associated primarily with environmental influences. Here we selectively review recent functional (fMRI) and structural (sMRI) magnetic resonance imaging research on DBD, focusing particularly on the role of CU traits. First, fMRI studies examining the neural correlates of affective stimuli, emotional face processing, empathy, theory of mind, morality, and decision-making in DBD are discussed. This is followed by a review of the studies investigating brain structure and structural connectivity in DBD. Next, we highlight the need to further investigate females and the role of sex differences in this population. We conclude the review by identifying potential clinical implications of this research.
The spatio-temporal organization of DNA replication sites is identical in primary, immortalized and transformed mammalian cells

We investigated the organization of DNA replication sites in primary (young or presenescent), immortalized and transformed mammalian cells. Four different methods were used to visualize replication sites: in vivo pulse-labeling with 5-bromo-2′-deoxyuridine (BrdU), followed by either acid depurination, or incubation in nuclease cocktail to expose single-stranded BrdU-substituted DNA regions for immunolabeling; biotin-dUTP labeling of nascent DNA by run-on replication within intact nuclei and staining with fluorescent streptavidin; and, finally, immunolabeling of the replication fork proteins PCNA and RPA. All methods produced identical results, demonstrating no fundamental differences in the spatio-temporal organization of replication patterns between primary, immortal or transformed mammalian cells. In addition, we did not detect a spatial coincidence between the early firing replicons and nuclear lamin proteins, the retinoblastoma protein or the nucleolus in primary human and rodent cells. The retinoblastoma protein does not colocalize in vivo with members of the Mcm family of proteins (Mcm2, 3 and 7) at any point of the cell cycle and neither in the chromatin-bound nor in the soluble nucleoplasmic fraction. These results argue against a direct role for the retinoblastoma or nuclear lamin proteins in mammalian DNA synthesis under normal physiological conditions.
Air pollution and lung cancer in Trieste, Italy: spatial analysis of risk as a function of distance from sources.

To investigate the relationship between four sources of environmental pollution (shipyard, iron foundry, incinerator, and city center) and lung cancer risk, we conducted a case-control study of decreased men in Trieste, Italy. We identified 755 cases of lung cancer and 755 controls through the local autopsy registry. Information on smoking habits, occupational history, and place of residence were obtained from the subject's next of kin. The case-control design was used to properly account for subject-specific confounders, which represent a major problem in geographical analysis. Spatial models were used to evaluate the effect of sources of pollution on lung cancer after adjustment for age, smoking habits, likelihood of exposure to occupational carcinogens, and levels of air particulate. The models are based on distance from the sources and enable estimation of the risk gradient and directional effects separately for each source. The risk of lung cancer was highly related to the city center (p = 0.0243), with an excess relative risk at zero distance of 2.2 and a smooth decrease moving away from the source (-0.015), and related to the incinerator (p = 0.0098), with an excess relative risk of 6.7 in the source and a very steep decrease (-0.176). These results are consistent with findings of previous analyses and provide further evidence that air pollution is a moderate risk factor of lung cancer. ImagesFigure 1.Figure 2.Figure 3
Is there an association between anxiety/depression and temporomandibular disorders in college students?

Objective Considering the high incidence of Temporomandibular Disorders (TMD) in the population aged 15-30 years and the fact that students are exposed to stressful psychosocial factors, the purposes of this study were: to verify clinical symptoms and jaw functionality in college students with TMD according to the anxiety/depression (A/D) level and to evaluate the correlation between A/D and functionality, maximum mouth opening (MMO) and pain and muscle activity. Material and Methods Nineteen students with TMD diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorders underwent two assessments during an academic semester. The evaluations were based on questionnaires (MFIQ - Mandibular Function Impairment Questionnaire; HADS - Hospital Anxiety and Depression Scale), clinical measurements (MMO without pain, MMO and assisted MMO; palpation of joint and masticatory muscles), and electromyography. The HADS scores obtained in the two assessments were used to classify all data as either "high" or "low" A/D. Data normality, differences and correlations were tested with the Shapiro-Wilk test, Student's t-test (or the Wilcoxon test), and Spearman test, respectively. The alpha level was set at 0.05. Results None of the clinical variables were significantly different when comparing low and high A/D data. In low A/D there was a significant correlation between HADS score and: MFIQ (P=0.005, r=0.61), and MMO without pain (P=0.01, r=-0.55). Conclusions Variation in A/D level did not change clinical symptoms or jaw functionality in college students with TMD. Apparently, there is a correlation between TMJ functionality and A/D level, which should be further investigated, taking into account the source of the TMD and including subjects with greater functional limitation.
Multiple Compound-Related Adverse Properties Contribute to Liver Injury Caused by Endothelin Receptor Antagonists

Drug-induced liver injury has been observed in patients treated with the endothelin receptor antagonists sitaxentan and bosentan, but not following treatment with ambrisentan. The aim of our studies was to assess the possible role of multiple contributory mechanisms in this clinically relevant toxicity. Inhibition of the bile salt export pump (BSEP) and multidrug resistance-associated protein 2 was quantified using membrane vesicle assays. Inhibition of mitochondrial respiration in human liver–derived HuH-7 cells was determined using a Seahorse XFe96 analyzer. Cytochrome P450 (P450)–independent and P450-mediated cell toxicity was assessed using transfected SV40-T-antigen–immortalized human liver epithelial (THLE) cell lines. Exposure-adjusted assay ratios were calculated by dividing the maximum human drug plasma concentrations by the IC50 or EC50 values obtained in vitro. Covalent binding (CVB) of radiolabeled drugs to human hepatocytes was quantified, and CVB body burdens were calculated by adjusting CVB values for fractional drug turnover in vitro and daily therapeutic dose. Sitaxentan exhibited positive exposure-adjusted signals in all five in vitro assays and a high CVB body burden. Bosentan exhibited a positive exposure-adjusted signal in one assay (BSEP inhibition) and a moderate CVB body burden. Ambrisentan exhibited no positive exposure-adjusted assay signals and a low CVB body burden. These data indicate that multiple mechanisms contribute to the rare, but potentially severe liver injury caused by sitaxentan in humans; provide a plausible rationale for the markedly lower propensity of bosentan to cause liver injury; and highlight the relative safety of ambrisentan.
Path-SGD: Path-Normalized Optimization in Deep Neural Networks

We revisit the choice of SGD for training deep neural networks by reconsidering the appropriate geometry in which to optimize the weights. We argue for a geometry invariant to rescaling of weights that does not affect the output of the network, and suggest Path-SGD, which is an approximate steepest descent method with respect to a path-wise regularizer related to max-norm regularization. Path-SGD is easy and efficient to implement and leads to empirical gains over SGD and Ada-Grad.
Geometric Protean Graphs

Abstract We study the link structure of online social networks (OSNs) and introduce a new model for such networks that may help in inferring their hidden underlying reality. In the geo-protean (GEO-P) model for OSNs, nodes are identified with points in Euclidean space, and edges are stochastically generated by a mixture of the relative distance of nodes and a ranking function. With high probability, the GEO-P model generates graphs satisfying many observed properties of OSNs, such as power-law degree distributions, the small-world property, densification power law, and bad spectral expansion. We introduce the dimension of an OSN based on our model and examine this new parameter using actual OSN data. We discuss how the geo-protean model may eventually be used as a tool to group users with similar attributes using only the link structure of the network.
The Gray filtration on phantom maps

This paper is a study of the Gray index of phantom maps. We give a new, tower theoretic, definition of the Gray index, which allows us to study the naturality properties of the Gray index in some detail. McGibbon and Roitberg have shown that if f∗ is surjective on rational cohomology, then the induced map on phantom sets is also surjective. We show that if f ∗ is surjective just in dimension k, then f induces a surjection on a certain subquotient of the phantom set. If the condition holds for all k, we recover McGibbon and Roitberg’s theorem. There is a dual result, and a theorem on phantom maps into spheres which holds one dimension at a time as well. Finally, we examine the set of phantom maps whose Gray index is infinite. The main theorem is a partial verification of our conjecture that if X and Y are nilpotent and of finite type, then every phantom map f : X −→Y must have finite index. Math. Subject Classifications: 55S37, 55P30, 55P62, 20G10, 20J05
Influence of Experimental Parameters on Fatigue Crack Growth and Heat Build-Up in Rubber

Loading parameters (frequency, amplitude ratio and waveform) are varied to determine their influence on fatigue crack growth in rubber. Up to three different rubber blends are investigated: one actual engineering material and two model materials. Fatigue crack growth curves and strain distributions of pure shear and faint waist pure shear samples are compared for a model material. Fatigue behavior is studied for three different frequencies (1 Hz, 3 Hz and 5 Hz). Amplitude ratio appears to be another important influence factor concerning fatigue crack growth in rubber. The beneficial effect of positive amplitude ratios (tensional loading conditions) is shown for different materials. However, fatigue crack growth is considerably increased for negative amplitude ratios (tensional-compressional loading conditions). Furthermore, the influence of the waveform is determined for three different waveform shapes. One is sinusoidal, and two have a square shape, including dwell periods and sinusoidal slopes. Special focus lies on heat build-up, which is substantial, especially for large loads, high frequencies and/or highly filled rubber blends. Plateau temperatures are determined for various loading conditions and rubber blends. A very simple linear relationship with dissipated energy per time and unit area is obtained. Results gathered with dynamic mechanical analyses show, likewise, a linear trend, but the heat build-up is very small, due to different sample geometries.
One‐Pot Reaction to Synthesize Biocompatible Magnetite Nanoparticles

Biocompatible magnetite nanocrystals (see Figure) are prepared by thermal decomposition of ferric triacetylacetonate in 2-pyrrolidone in the presence of monocarboxyl-terminated poly(ethylene glycol) (MPEG-COOH). The results reveal that MPEG is covalently bound to the nanocrystal surface by COOH groups. Magnetic resonance imaging (MRI) experiments indicate that the coated nanocrystals are potential MRI contrast agents due to their excellent water solubility and biocompatibility.
Dynamic Assessment of Reading Difficulties: Predictive and Incremental Validity on Attitude toward Reading and the Use of Dialogue/Participation Strategies in Classroom Activities

Dynamic Assessment (DA) has been shown to have more predictive value than conventional tests for academic performance. However, in relation to reading difficulties, further research is needed to determine the predictive validity of DA for specific aspects of the different processes involved in reading and the differential validity of DA for different subgroups of students with an academic disadvantage. This paper analyzes the implementation of a DA device that evaluates processes involved in reading (EDPL) among 60 students with reading comprehension difficulties between 9 and 16 years of age, of whom 20 have intellectual disabilities, 24 have reading-related learning disabilities, and 16 have socio-cultural disadvantages. We specifically analyze the predictive validity of the EDPL device over attitude toward reading, and the use of dialogue/participation strategies in reading activities in the classroom during the implementation stage. We also analyze if the EDPL device provides additional information to that obtained with a conventionally applied personal-social adjustment scale (APSL). Results showed that dynamic scores, obtained from the implementation of the EDPL device, significantly predict the studied variables. Moreover, dynamic scores showed a significant incremental validity in relation to predictions based on an APSL scale. In relation to differential validity, the results indicated the superior predictive validity for DA for students with intellectual disabilities and reading disabilities than for students with socio-cultural disadvantages. Furthermore, the role of metacognition and its relation to the processes of personal-social adjustment in explaining the results is discussed.
ELECTRON MICROSCOPY OF VIRUSES OF HUMAN PAPILLOMA, MOLLUSCUM CONTAGIOSUM, AND VACCINIA, INCLUDING OBSERVATIONS ON THE FORMATION OF VIRUS WITHIN THE CELL

This discussion will deal with electron microscopic studies of two lesions of human skin, papilloma and molluscum contagiosum. Both diseases are infectious, the etiological agents being filterable. Work on these viruses has been limited, however, in that the only known host is man. Our work on human papilloma was carried out in conventional fashion, i . e . , isolation of cellular components by differential centrifugation and their examination in the electron microscope. Molluscum contagiosum was studied in the same way, but, in addition, infected cells have been cut in thin sectionsand thevirus examined in situ. For purposes of comparison, thin sections of vacciniavirus-infected cells of the chorio-allantoic membrane have been studied. I t will soon become obvious that two pox viruses do not necessarily multiply in the same fashion.