Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of V3 Independent Domains on a Dualtropic Human Immunodeficiency Virus Type 1 (HIV‐1) Envelope gp120 in CCR5 Coreceptor Utilization and Viral Infectivity

The molecular mechanism of human immunodeficiency virus type 1 (HIV‐1) entry into cells involves specific interactions between the viral envelope glycoprotein gp120 and two target cell proteins, CD4 and either CCR5 or CXCR4 chemokine receptors. In order to delineate the functional role of HIV‐1 gp120 subdomains of dualtropic strains in CCR5 coreceptor usage, we used a panel of chimeric viruses in which the V1/V2 and V3 domains of gp120 from the dualtropic HIV‐1KMT isolate were introduced either alone or in combination into the T‐tropic HIV‐1NL4–3 background. These chimeric constructs were employed in cell‐cell fusion and cell‐free virus infectivity assays using cell lines expressing CD4 and the CCR5 chemokine receptor. In both assays, the V3 domain of HIV‐1KMT but not the V1/V2 domain proved to be the principal determinant of CCR5 coreceptor usage. However, in the cell‐free viral infectivity assay although a chimeric virus with a combined V1/V2 and V3 domains of HIV‐1KMT efficiently fused with coreceptor expressing cells, yet its infectivity was markedly diminished in CCR5 as well as CXCR4 expressing cells. Restoring a comparable level of infection of such chimeric virus required the C3‐V5 domain from HIV‐1KMT to be introduced. Our present findings confirmed that the V3 domain is the major determinant of fusion activity and cellular tropism, and demonstrated a dispensable role for the V1/V2 domain. In addition the C3‐V5 domain appeared to play an important role in viral infectivity when the corresponding V1/V2 and V3 domains are present.
Overarching challenges to the implementation of competency-based medical education

Abstract Medical education is under increasing pressure to more effectively prepare physicians to meet the needs of patients and populations. With its emphasis on individual, programmatic, and institutional outcomes, competency-based medical education (CBME) has the potential to realign medical education with this societal expectation. Implementing CBME, however, comes with significant challenges. This manuscript describes four overarching challenges that must be confronted by medical educators worldwide in the implementation of CBME: (1) the need to align all regulatory stakeholders in order to facilitate the optimization of training programs and learning environments so that they support competency-based progression; (2) the purposeful integration of efforts to redesign both medical education and the delivery of clinical care; (3) the need to establish expected outcomes for individuals, programs, training institutions, and health care systems so that performance can be measured; and (4) the need to establish a culture of mutual accountability for the achievement of these defined outcomes. In overcoming these challenges, medical educators, leaders, and policy-makers will need to seek collaborative approaches to common problems and to learn from innovators who have already successfully made the transition to CBME.
Phosphatidic acid regulates the affinity of the murine phosphatidylinositol 4‐phosphate 5‐kinase‐Iβ for phosphatidylinositol‐4‐phosphate

Type I phosphatidylinositol 4‐phosphate 5‐kinase (PI4P5K) catalyzes the phosphorylation of phosphatidylinositol 4 phosphate [PI(4)P] at carbon 5, producing phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2]. Phosphatidic acid (PA) activates PI4P5K in vitro and plays a central role in the activation of PIP5K pathways in vivo. This report demonstrates that actin fiber formation in murine fibroblasts involves PA activation of PIP5Ks and defines biochemical interactions between PA and the PIP5Ks. Inhibition of phospholipase D production of PA results in the loss of actin fibers. Overexpression of the beta isoform of the type I murine phosphatidylinositol 4‐phosphate 5‐kinase (mPIP5K‐Iβ) maintains actin fiber structure in the face of phospholipase D inhibition. PA activates mPIP5K‐Iβ by direct binding to mPIP5K‐Iβ through both electrostatic and hydrophobic interactions, with the fatty acid acyl chain length and degree of saturation acting as critical determinants of binding and activation. Furthermore, kinetic analysis suggests that phosphorylation of the PI(4)P substrate does not follow classical Michaelis–Menten kinetics. Instead, the kinetic data are consistent with a model in which mPIP5K‐Iβ initially binds to the lipid micelle and subsequently binds the PI(4)P substrate. In addition, the kinetics indicate substrate inhibition, suggesting that mPIP5K‐Iβ contains an inhibitory PI(4)P‐binding site. These results suggest a model in which mPIP5K‐Iβ is surrounded by PI(4)P, but is unable to catalyze its conversion to PI(4,5)P2 unless PA is bound. J. Cell. Biochem. 100: 112–128, 2007. © 2006 Wiley‐Liss, Inc.
Noninvasive prenatal diagnosis of fetal aneuploidies and Mendelian disorders: new innovative strategies

The application of recent technical developments, such as digital PCR or shot-gun sequencing, for the analysis of cell-free fetal DNA, have indicated that the long-sought goal of the noninvasive detection of Down syndrome may finally be attained. Although these methods are still cumbersome and not high throughput, they provide a paradigm shift in prenatal diagnosis, as they could effectively pronounce the end of invasive procedures, such as amniocentesis or chorionic villous sampling for the detection of such fetal anomalies. However, it remains to be determined how suitable these approaches are for the detection of more subtle fetal genetic alterations, such as those involved in hereditary Mendelian disorders (e.g., thalassemia and cystic fibrosis). New technical developments, such as microfluidics and reliable automated scanning microscopes, have indicated that it may be possible to efficiently retrieve and examine circulating fetal cells. As these contain the entire genomic complement of the fetus, future developments may include the noninvasive determination of the fetal karyotype.
Past Suicide Attempts in Depressed Inpatients: Clinical versus Research Assessment

The objective of this study was to compare structured clinical assessment versus research measurement of suicidal risk among inpatients with major depression. Fifty depressed inpatients underwent a structured clinical and an independent research assessment of suicidal risk. Agreement between both assessments and its impact upon time to first readmission was tested. A false negative rate of 25% in the clinical screening of past suicide attempts was associated with older age, concealment, and reported lower frequency of suicidal thoughts. Mean times to first readmission (2.5 years follow-up) were 74 weeks (discordant responders) and 118 weeks (concordant responders). A failure to detect 25% of patients with past suicide attempt history in the clinical assessment was associated with older age and concealment of suicidal thoughts.
A human 200-kDa protein binds selectively to DNA fragments containing G.T mismatches.

G.T mispairs, the sole mismatch type that can arise in "resting" mammalian DNA (through spontaneous hydrolytic deamination of 5-methylcytosine), are corrected in vivo with high efficiency and mostly to a G.C. We identified a protein factor, present in HeLa cell extracts, that binds selectively to DNA substrates containing this mismatch. The partially purified protein was shown by gel-filtration chromatography and UV cross-linking experiments to have an apparent molecular mass of 200 kDa. Its binding to G.T mispairs was not influenced by sequences flanking the mismatch, but methylation of guanines either within the mismatch itself or in its immediate vicinity abolished the formation of the protein-DNA complex. The protein appears to lack both endo- and exonuclease activities and requires neither magnesium nor zinc nor ATP for binding. We discuss the possible role of this protein in a repair pathway, which helps mammalian cells counter the mutagenic effect of the hydrolytic deamination of 5-methylcytosine.
Heterogeneous Oxidation by Ozone of Naphthalene Adsorbed at the Air-Water Interface of Micron-Size Water Droplets

Abstract The mass transfer of naphthalene vapor to water droplets in air was studied in the presence of ozone (O3) in the gas phase. A falling droplet reactor with water droplets of diameters 55, 91, and 182 μm was used for the study. O3 reacted with naphthalene at the air-water interface, thereby decreasing the mass transfer resistance and increasing the rate of uptake of naphthalene into the droplet. A Langmuir-Hinshelwood reaction mechanism at the air-water interface satisfactorily described the surface reaction. The first-order surface reaction rate constant, ks, increased with decreasing droplet size. Three organic intermediates were identified in the aqueous phase as a result of ozonation of naphthalene at the surface of the droplet indicating both peroxidic and nonperoxidic routes for ozonation. The presence of an organic carbon surrogate (fulvic acid) increased both the partition constant of naphthalene and the surface reaction rate of O3. The heterogeneous oxidation of naphthalene by O3 on the droplet was 15 times faster than the homogeneous oxidation by O3 in the bulk air phase, whereas it was only 0.08 times the homogeneous gas-phase oxidation by hydroxyl radicals under atmospheric conditions.
Weather Factors Influencing the Population Dynamics of Culex pipiens (Diptera: Culicidae) in the Po Plain Valley, Italy (1997–2011)

ABSTRACT The impact of weather variables on Culex pipiens L. (Diptera: Culicidae) population dynamics in the Po Valley, Northern Italy, a densely populated region containing the largest industrial and agricultural areas in Italy, was investigated. Monitoring of mosquitoes was carried out by using CO2-baited traps without light, collecting data weekly from 1700 to 0900 hours during the period May–September, from 1997 to 2011. Daily minimum, average, and maximum relative humidity; daily minimum, maximum, and average temperature; rainfall; and hydroclimatic balance (rainfall-potential evapotranspiration) were obtained from three weather stations within the surveillance zone. The average population dynamic trend over the 15-yr period showed a bell-shaped curve with a major peak in June and a secondary peak at the end of August in the rural areas, whereas bimodality was not evidenced in the urban areas. The correlation analyses showed that the mosquito seasonal population and the population in the period of maximum West Nile virus circulation (August–September) was mostly affected by the relative humidity registered from March to July, particularly in May, and, to a lower extent, also by hydroclimatic balance registered in April–July, and by the rainfall occurred in June–July. In addition, the rate of increase of the population during the spring months influenced the development of the mosquito population of the following months.
Passive transfer of Sjogren's syndrome IgG produces the pathophysiology of overactive bladder.

OBJECTIVE The presence, in patients with primary and secondary Sjogren's syndrome (SS), of autoantibodies that acutely inhibit M(3) muscarinic receptor (M3R)-mediated bladder contractions is difficult to reconcile with the fact that symptoms of detrusor overactivity and other features of cholinergic hyperresponsiveness occur in this disease. This study was undertaken to examine the in vivo effects of these autoantibodies on bladder function by examining bladder responsiveness and compliance following passive transfer of patient IgG to mice. METHODS Contractile responses of isolated bladder strips both to the muscarinic agonist carbachol and to electrically evoked acetylcholine release were measured 48 hours after injection of mice with patient or control IgG. A whole bladder assay with intact neuronal pathways was developed to assess bladder wall compliance on filling cystometry. Expression of M3R in bladders from IgG-injected mice was assessed by immunohistochemistry. RESULTS Passive transfer of SS IgG with inhibitory anti-M3R activity produced a paradoxical increase in contractile responses of detrusor strips to cholinergic stimulation. Cystometry of whole bladders revealed a corresponding decrease in bladder wall compliance and phasic detrusor contractions upon filling, replicating the urodynamic features of an overactive bladder. The features of cholinergic hyperresponsiveness were associated with increased postsynaptic M3R expression and were reproduced by injecting mice with a rabbit antibody against the second extracellular loop of M3R. CONCLUSION These findings are consistent with the notion that there is initial inhibition of parasympathetic neurotransmission by antagonistic autoantibodies to M3R, which produces a compensatory increase in M3R expression in vivo. The enhanced cholinergic responses during bladder distention result in detrusor overactivity. We conclude that the overactive bladder associated with SS is an autoantibody-mediated disorder of the autonomic nervous system, which may be part of a wider spectrum of cholinergic hyperresponsiveness.
Regulation of Sprouty2 stability by mammalian Seven‐in‐Absentia homolog 2

Mammalian Sprouty (Spry) gene expression is rapidly induced upon activation of the FGF receptor signaling pathway in multiple cell types including cells of mesenchymal and epithelial origin. Spry2 inhibits FGF‐dependent ERK activation and thus Spry acts as a feedback inhibitor of FGF‐mediated proliferation. In addition, Spry2 interacts with the ring‐finger‐containing E3 ubiquitin ligase, c‐Cbl, in a manner that is dependent upon phosphorylation of Tyr55 of Spry2. This interaction results in the poly‐ubiquitination and subsequent degradation of Spry2 by the proteasome. Here, we describe the identification of another E3 ubiquitin ligase, human Seven‐in‐Absentia homolog‐2 (SIAH2), as a Spry2 interacting protein. We show by yeast two‐hybrid analysis that the N‐terminal domain of Spry2 and the ring finger domain of SIAH2 mediated this interaction. Co‐expression of SIAH2 resulted in proteasomal degradation of Spry1, 2, and to a lesser extent Spry4. The related E3 ubiquitin‐ligase, SIAH1, had little effect on Spry2 protein stability when co‐expressed. Unlike c‐Cbl‐mediated degradation of Spry2, SIAH2‐mediated degradation was independent of phosphorylation of Spry2 on Tyr55. Spry2 was also phosphorylated on Tyr227, and phosphorylation of this residue was also dispensable for SIAH2‐mediated degradation of Spry2. Finally, co‐expression of SIAH2 with Spry2 resulted in a rescue of FGF2‐mediated ERK phosphorylation. These data suggest a novel mechanism whereby Spry2 stability is regulated in a manner that is independent of tyrosine phosphorylation, and provides an addition level of control of Spry2 protein levels. J. Cell. Biochem. 100: 151–160, 2007. © 2006 Wiley‐Liss, Inc.
Developmental timing of mutations revealed by whole-genome sequencing of twins with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the major pediatric cancer. At diagnosis, the developmental timing of mutations contributing critically to clonal diversification and selection can be buried in the leukemia's covert natural history. Concordance of ALL in monozygotic, monochorionic twins is a consequence of intraplacental spread of an initiated preleukemic clone. Studying monozygotic twins with ALL provides a unique means of uncovering the timeline of mutations contributing to clonal evolution, pre- and postnatally. We sequenced the whole genomes of leukemic cells from two twin pairs with ALL to comprehensively characterize acquired somatic mutations in ALL, elucidating the developmental timing of all genetic lesions. Shared, prenatal, coding-region single-nucleotide variants were limited to the putative initiating lesions. All other nonsynonymous single-nucleotide variants were distinct between tumors and, therefore, secondary and postnatal. These changes occurred in a background of noncoding mutational changes that were almost entirely discordant in twin pairs and likely passenger mutations acquired during leukemic cell proliferation.
Fragmented QRS complexes are associated with left ventricular dysfunction in patients with type-2 diabetes mellitus: a two-dimensional speckle tracking echocardiography study

Abstract Background: Heart failure may develop independently of coronary artery disease in diabetes mellitus (DM) patients. Fragmented QRS (fQRS) is a marker of myocardial fibrosis or scar tissue and is related to an increase in cardiovascular adverse events. In this study, we examined the utility of speckle tracking echocardiography (STE) in assessing LV function in DM patients with fQRS. Methods and Results: The current study included 178 consecutive patients diagnosed with type-2 DM. The patients included were separated into two groups: those with (n = 50) and without (n = 128) fQRS. The two groups were compared by obtaining LV strain values with STE. Statistically significant differences were also identified between fQRS(−) and fQRS (+) groups with respect to Lv-GLS (p < .001), maxLAVI (p = .020), minLAVI (p < .001), E velocity (p < .001), Em velocity (0.002), E/Em ratio (<0.001) SRe (p < .001), SRe/SRa ratio (p < .001), SRivr (p < .001) and E/SRivr ratio (p < .001). In the multiple linear regression analysis, fQRS (β = −2.077, p = .002) and DM duration (β = −0.216, p = .021) were identified as independent predictors of Lv-GLS. However, fQRS (β = 4.557, p = .001) and minLAVI (β = −2.198, p = .031) were also found to be independent predictors of E/SRivr. We also performed multiple logistic regression analysis and identified Lv-GLS (β = −0.557, p = .001), minLAVI (β = −0.769, p = .001), E/Em ratio (β = 0.650, p = .001) and E/SRivr (β = 0.105, p = .001) as independent predictors of fQRS. Conclusıons: The results of this study revealed that subclinical LV dysfunction was more common in diabetic patients with fQRS. Therefore, determination of fQRS could be an indicator of the diabetic CMP in patients with DM.
Perspectives on power-aware electronics

In the coming ubiquitous-IT society, low-power design is one of the key features at which the VLSI designer should aim. Otherwise, power increase will remain as one of the main obstacles to Moore's law growth. Unless VLSI power is lowered by orders of magnitude, we cannot enjoy the progress that scaling offers. This talk will cover what we now have, and what we should provide in our low-power armory to allow us to cope with ever-increasing leakage loss, as well as dynamic power. The techniques to be presented range over the system, software, circuit, and device levels including interconnect and I/O issues. The novel trend is to examine cooperative approaches between levels such as software-circuit cooperation and circuit-technology cooperation. The biggest challenge that System-on-Chip designers must resolve in the future is the fact that transistors for digital and memory circuits will be more and more leaky as technology generations advance. Approaches to solving this serious problem will be described. Beyond the quest for low-power solutions lies a promising world of ubiquitous VLSI devices and products ranging from "wireless sensors and tags for everything" to "everything-you-must-do mobile terminals".
Fabrication and Characterization of Proton-Exchanged Waveguide on X-Cut LiNbO3

In this letter, we report proton-exchanged (PE) slab and channel waveguides fabricated on x-cut lithium niobate. The thickness and the optical constants as well as the composition profiles of the PE films at different PE hours are measured using prism coupling technique and secondary ion mass spectroscopy method. Planar and channel waveguide structures are characterized and an 8 times 8 square array of air holes on PE LiNbO3 waveguide is demonstrated using focused ion beam.
Sequencing of a New Target Genome: the Pediculus humanus humanus (Phthiraptera: Pediculidae) Genome Project

Abstract The human body louse, Pediculus humanus humanus (L.), and the human head louse, Pediculus humanus capitis, belong to the hemimetabolous order Phthiraptera. The body louse is the primary vector that transmits the bacterial agents of louse-borne relapsing fever, trench fever, and epidemic typhus. The genomes of the bacterial causative agents of several of these aforementioned diseases have been sequenced. Thus, determining the body louse genome will enhance studies of host–vector–pathogen interactions. Although not important as a major disease vector, head lice are of major social concern. Resistance to traditional pesticides used to control head and body lice have developed. It is imperative that new molecular targets be discovered for the development of novel compounds to control these insects. No complete genome sequence exists for a hemimetabolous insect species primarily because hemimetabolous insects often have large (2,000 Mb) to very large (up to 16,300 Mb) genomes. Fortuitously, we determined that the human body louse has one of the smallest genome sizes known in insects, suggesting it may be a suitable choice as a minimal hemimetabolous genome in which many genes have been eliminated during its adaptation to human parasitism. Because many louse species infest birds and mammals, the body louse genome-sequencing project will facilitate studies of their comparative genomics. A 6–8× coverage of the body louse genome, plus sequenced expressed sequence tags, should provide the entomological, evolutionary biology, medical, and public health communities with useful genetic information.
Margin Maximum Embedding Discriminant (MMED) for Feature Extraction and Classification

This paper develops a supervised discriminant technique, called Margin Maximum Embedding Discriminant (MMED), for dimensionality reduction of high-dimensional data. In graph embedding, our objective is to find a linear transform matrix to make the samples in the same class as compact as possible and the samples belong to the different classes as dispersed as possible. The proposed method effectively avoids the singularity problem frequently encountered in the classical linear discriminant analysis due to the small sample size (SSS) and overcomes the limitations of the traditional linear discriminant analysis algorithm (LDA) due to data distribution assumptions and available projection directions. Experimental results on ORL and AR face databases show the effectiveness of the proposed method
3D modeling and augmented reality

In this talk, I will first introduce our research on 3D modeling. For 3D geometry modeling, we present a rapid method to align large sets of 3D scanned data automatically. We articulate a novel approach to geometric model completion via interactive sketches. For appearance modeling, we present a new method for modeling real-world surface reflectance, described with non-parametric spatially-varying bidirectional reflectance distribution functions (SVBRDF). Then I will show our Augmented Reality Aided Jet Engine Assembly and Disassembly Guidance System. In this system, context-aware text instructions, video clips and virtual assembly/disassembly demonstrations are displayed on demand as an overlay in head-mounted displays (HMD); hands-free voice interfaces are used for user interaction; operations are synchronized wirelessly among different technicians and controlled with a dedicated work flow server.
When do firms focus on public research? : evidence from U.S. medical device industry

ABSTRACT Public research including universities and research institutes is an important source of innovation. This paper describes how a performance feedback model explains the conditions under which firms source external knowledge through universities and research institutes. In the U.S. medical device industry, we show that there is an inverted U-shaped relationship between performance below aspirations and knowledge sourcing from public research. Furthermore, we find that firms respond to historical aspirations more sensitively than social aspirations, and slack resources tend to attenuate the relationship between performance below historical aspirations and knowledge sourcing from public research.