Miracle-dz/UniFAR-FTUs huggingface dataset:
A Conserved Domain and Membrane Targeting of Nef from HIV and SIV Are Required for Association with a Cellular Serine Kinase Activity (*)

Among the primate lentiviruses (human immunodeficiency virus (HIV) −1, HIV-2, and simian immunodeficiency virus (SIV)), the nef gene is highly conserved and encodes a myristylated protein of 27 kDa (HIV-1) or 34 kDa (HIV-2, SIV). Previously, we found Nef expressed either as a CD8-Nef fusion protein or as a native protein in virally infected T cell lines associates with a cellular serine kinase. This kinase activity phosphorylated two proteins of 62 and 72 kDa that coimmunoprecipitate with Nef in in vitro kinase assays. Using transient expression, various Nef alleles and mutants have been analyzed for association with the cellular kinase activity. The ability of Nef to associate with the kinase activity is conserved among several alleles of HIV-1 as well as SIV and is observed in non-lymphoid cell lines of simian and murine origins. Two separate regions of HIV-1 Nef are critical for the associated kinase activity. One domain overlaps with a central highly conserved region found in all primate lentivirus nef genes and has been provisionally mapped to amino acids 45-127. Because membrane localization of Nef is important for the associated cellular kinase activity, the second domain represents a membrane targeting signal. Moreover, point mutations within the central region that abrogate the Nef-associated kinase activity in HIV-1 Nef have the same effect when introduced into SIV Nef.
Conditioned media from mouse osteosarcoma cells promote MC3T3‐E1 cell proliferation using JAKs and PI3‐K/Akt signal crosstalk

The maintenance of bone mass requires a strict balance between bone formation by osteoblasts and bone resorption by osteoclasts. In tumoral bone environment, tumor cells frequently disturb this balance by interaction with bone cells to create a favorable site for tumor growth, and promote pathological bone changes. Thus, elucidation of the mechanisms underlying interaction between tumor cells and bone cells might eventually lead to a more rational strategy for therapeutic intervention for bone tumors and better understanding of bone biology. In the present study, the effects of mouse osteosarcoma cells on mouse preosteoblastic cells were determined by assessment of cell viability, osteoblastic differentiation and signal transduction pathways. MOS‐J/POS‐1 conditioned media (CM) significantly induced MC3T3‐E1 cell proliferation in a dose‐dependent manner and reduced both alkaline phosphatase activity and mineralized nodule formation. Piceatannol, AG490, LY294002 and rapamycin significantly abrogated this up‐regulated cell proliferation; however, UO126 and STAT3 inhibitor peptide did not affect this up‐regulated cell proliferation. MOS‐J/POS‐1 CM activated ERK 1/2, STAT3 and Akt signal transduction pathways; however, pro‐proliferating signal induced by MOS‐J/POS‐1 CM was transmitted via Akt not ERK 1/2 and STAT3 pathways. Furthermore, Western blot analyses clearly revealed novel signal crosstalk between JAKs and PI3‐K/Akt in osteoblastic cells. The specific factor(s) involved in MOS‐J/POS‐1 CM‐induced MC3T3‐E1 cell proliferation that use JAKs/PI3‐K/Akt/mTOR pathway remain(s) to be determined. Determination of the specific factor(s) responsible for JAKs and PI3‐K/Akt signal crosstalk that results in up‐regulated preosteoblast proliferation will offer new insight into the pathology of osteosarcoma as well as other bone‐related diseases. (Cancer Sci 2008; 99: 2170–2176)
A Critique of Current Diagnostic Criteria for Attention Deficit Hyperactivity Disorder: Clinical and Research Implications

The present paper critiques the current diagnostic criteria from the DSM-III-R and the draft criteria proposed for the ICD-10 for attention deficit hyperactivity disorder (ADHD). Improvements made in the criteria over earlier editions are discussed along with continuing limitations in these approaches to clinical diagnosis. The issue of whether ADHD constitutes an actual syndrome is also reviewed. It is concluded that despite contradictory evidence for covariation of the symptoms, the disorder meets other important conditions for syndrome definition and should continue to be viewed as such. The variability of symptoms across settings and parameters which may affect this variability are briefly noted as is the impact of this symptom instability on establishing diagnostic criteria. A number of suggestions for revision of these criteria are provided that can be incorporated into current clinical and research practices to improve the rigor and discriminative validity of the criteria for ADHD. The implications of these revisions for clinical diagnosis are also discussed.
Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease.

OBJECTIVE To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. DESIGN Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months. SETTING Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. SUBJECTS Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. INTERVENTIONS None. OUTCOME MEASURES Onset of chorea and imaging results. RESULTS The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. CONCLUSIONS The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism.
Bowel health to better health: a minimal contact lifestyle intervention for people at increased risk of colorectal cancer

Colorectal cancer screening forms part of Scotland's cancer reduction strategy. Screened participants, who had undergone colonoscopy and had adenoma(s) removed, were invited to participate in the bowel health to better health (BHBH) programme. BHBH tested the hypothesis that a minimal contact lifestyle intervention could prove effective in promoting changes in diet and activity. Baseline and follow-up questionnaires on lifestyle and psycho-social measures were undertaken in adults randomised to BHBH or a comparison group (CG). The 3-month intervention comprised personalised lifestyle advice, goal-setting and social support to promote increases in physical activity, fibre, fruit and vegetables. Response rate to BHBH was 51 %. BHBH participants (n 32) increased their intake of fibre (DINE FFQ scores 30 (sd 11)–41 (sd 13)) significantly (P < 0·001) more than the CG (n 30; 31 (sd 8)–30 (sd 11). No significant differences between the groups were detected for changes in fruits, vegetables and moderate activity. At baseline, only one participant from each study arm, met the target recommendations for fibre, fruit and vegetable intakes and physical activity. At follow up a significant number of BHBH participants, 15 (47 %) compared to 4 (13 %) of the CG were achieving all three lifestyle recommendations (χ2 (1, n 62) = 8·196, P = 0·006). If sustained, the positive behaviour change achieved through this intervention has the potential to impact on the progression of chronic disease risk including CVD.
Synchrony-Breaking Bifurcation at a Simple Real Eigenvalue for Regular Networks 2: Higher-Dimensional Cells

Bifurcation from a trivial branch of equilibria at a simple real eigenvalue can be characterized by a singularity-theoretic normal form $\lambda x \pm x^r$. The case $r=2$ corresponds to transcritical bifurcation and $r=3$ to pitchfork bifurcation. A previous paper [I. Stewart and M. Golubitsky, SIAM J. Appl. Dyn. Syst. , 10 (2011), pp. 1404--1442] discussed such bifurcations in the context of regular coupled cell networks. When cells are 1-dimensional, there exist networks in which all such bifurcations are 3-degenerate, that is, have normal forms with $r \geq 4$. We extend the analysis to cells of arbitrary dimension and prove that if the adjacency matrix has triangular eigenstructure, then the same degree of degeneracy occurs, subject to a mild condition on the linearization that ensures a simple eigenvalue. We give an example of a network without triangular eigenstructure where 3-degeneracy is not preserved for cells of dimension $\geq 2$.
Monitoring of glass derivatization with pulsed force mode atomic force microscopy

Non‐specific adsorption of proteins at solid/liquid interfaces is a major problem in the use of synthetic biomaterials and in ultrasensitive detection methods. Grafting surfaces with a dense layer of poly(ethylene glycol) (PEG) or other polymers is a most widely used strategy to solve this task. While such modified surfaces have been characterized by their ability to resist protein adsorption, the polymer layers themselves have rarely been studied in fine detail. Atomic force microscopy (AFM) using the pulsed force mode (PFM), is an ideal technique to investigate structural features and physiochemical properties of surfaces because topology and adhesion are simultaneously detected with high lateral resolution. In the present study, PFM‐AFM was applied to thoroughly characterize different stages of glass derivatization, up to the formation of a dense PEG layer. Lateral inhomogeneities in topology and/or adhesion were observed at all stages before PEG attachment. The covalently bound PEG, however, was seen to form a densely packed monolayer with maximal thickness, smooth surface, and weak adhesion. Thus, PFM‐AFM appears to be a valuable tool for the characterization of protein‐repelling surfaces in solution. Microsc. Res. Tech. 65:246–251, 2004. © 2005 Wiley‐Liss, Inc.
Atom optics realization of the quantum delta -kicked rotor.

We report the first direct experimental realization of the quantum d-kicked rotor. Our system consists of a dilute sample of ultracold sodium atoms in a periodic standing wave of near-resonant light that is pulsed on periodically in time to approximate a series of delta functions. Momentum spread of the atoms increases diffusively with every pulse until the “quantum break time" after which exponentially localized distributions are observed. Quantum resonances are found for specific values of the pulse period.
Voice Verification System for Mobile Devices based on ALIZE/LIA_RAL

The main contribution of this paper is providing an architecture for mobile users to authenticate user identity through short text phrases using robust open source voice recognition library ALIZE and speaker recognition tool LIA_RAL. Our architecture consists of a server connected to a group of subscribed mobile devices. The server is mainly needed for training the world model while user training and verification run on the individual mobile devices. The server uses a number of public random speaker text independent voice files to generate data, including the world model, used in training and calculating scores. The server data are shipped with the initial install of our package and with every subsequent package update to all subscribed mobile devices. For security purposes, training data consisting of raw voice and processed files of each user reside on the userâ? s device only. Verification is based on a short text-independent as well as text-dependent phrases, for ease of use and enhanced performance that gets processed and scored against the user trained model. While we implemented our voice verification in Android, the system will perform as efficiently in iOS. It will in fact be easier to implement since the base libraries are all written in C/C++. We show that the verification success rate of our system is 82%. Our system provides a free robust alternative to replace commercial voice identification and verification tools and extensible to implement more advanced mathematical models available in ALIZE and shown to improve voice recognition.
Effectiveness of different preventive procedures in the control of cariogenic risk factors in children

Caries risk assessment is a valuable clinical procedure that in many ways alleviates implementation of preventive procedures in high caries risk children. The aim of this study was to investigate the effectiveness of five different caries preventive procedures in vivo. A 100 children, divided in five groups, each with 20 children (aged 4-5 and 10-12 years) were treated with different preventive procedures (amine fluoride solution, professional prophylactic paste, chewing gum containing xylitol and fluoride, chlorhexidine solution, chlorhexidine-fluoride gel). During a period of two months five measurements were performed and the following variables evaluated: the number of Streptococcus mutans (SM) and Lactobacilli (LB), oral hygiene index (OHI) and the amount of stimulated saliva. Results showed that the highest reduction of the number of bacteria was achieved by the application of professional prophylactic paste and daily use of chewing gum containing xylitol and fluoride, (P<0.001). In these children the number of SM was reduced by class 1 and LB to <104 CFU/ml after two months. In conclusion, the professional teeth cleaning and use of chewing gum with xylitol and fluorides on daily basis could be very effective protocol for controlling the caries risk factors in children.
Subcentimeter thyroid nodules: utility of sonographic characterization and ultrasound-guided needle biopsy.

OBJECTIVE The purpose of this study is to examine subcentimeter thyroid nodules to determine their rate of malignancy, the accuracy of various ultrasound features in prediction of malignancy, and the utility of ultrasound-guided biopsy of these nodules. MATERIALS AND METHODS Included in this retrospective study were 104 patients in whom 108 thyroid nodules smaller than 1 cm had been biopsied. Diagnostic ultrasound examinations were reviewed, and nodules were evaluated for the following ultrasound features: internal echogenicity, margins, height-to-width ratio, presence of calcifications, posterior acoustic features, solid-to-cystic ratio, presence of a halo, and color Doppler characteristics. In addition, a subjective assessment of level of suspicion was assigned to each nodule. Each feature was correlated with the pathologic results to determine the accuracy of the feature for predicting malignancy. RESULTS Adequate cytologic specimens were obtained in 97 of the 108 subcentimeter biopsies (90%) performed. The average size of malignant nodules was significantly smaller than the average size of benign nodules (6.4 ± 2.1 vs 7.7 ± 1.4 mm, p = 0.041). The rate of carcinoma among nodules with a final diagnosis was 19% (16/85). The most accurate features significantly associated with malignancy were posterior acoustic shadowing (87%), many diffuse calcifications (82%), rim calcifications (81%), and taller than wide shape (79%). The subjective level of suspicion correlated well with the presence of malignancy (76%). CONCLUSION Subcentimeter nodules are significantly associated with the risk of malignancy and can be accurately and safely biopsied with a very high diagnostic rate. Certain ultrasound features can be used to accurately stratify risk of malignancy, although no single feature replaces the clinician's overall impression.
Beyond Wise et al.: Neuroleptic-induced “anhedonia” in rats: Pimozide blocks reward quality of food

O all the neurotransmitters in the brain the one that is best known to the lay public, by far, is dopamine (DA). To the public, and much of the media, DA is the brain’s “pleasure transmitter. ” By this popular view, it is a burst of DA that produces the pleasure associated with the receipt or anticipation of natural rewards – a chocolate cake, sex, even social rewards – as well as the euphoria produced by addictive drugs, such as amphetamine, cocaine or heroin. In the popular media it is often suggested that it is pursuit of this DA “rush” that leads to a variety of impulse control disorders, such as over-eating, gambling and addiction. Of all the ideas, in all of neuroscience, this is one of the most widely known, and its origin can be traced to the 1978 paper by Roy Wise, Joan Spindler, Harriet deWit and Gary Gerber, that is the topic of this chapter. This paper is an excellent example of how the interpretation of a seemingly simple experimental finding can profoundly influence the thinking and trajectory of an entire field, and the public imagination, for decades – even if it is wrong. But before getting to that conclusion, we should step back and consider the time leading up to the publication of this extremely influential paper. It was only a little over a decade earlier that DA was first recognized as a neurotransmitter in its own right (rather than just being a precursor of norepinephrine). This came about from a series of important studies by researchers in Sweden who developed a histofluorescence method to identify and map monoamine neurotransmitters in the brain (including DA). They thus effectively created the field of chemical neuroanatomy, as well as vividly mapping the location of dopamine in the brain. They also produced useful methods to selectively lesion monoamine-containing cells with neurotoxins, such as 6-hydroxydopamine (6-OHDA), which would help reveal dopamine’s psychological functions via behavioral consequences. As a result of these studies it became clear that DA-producing neurons located in the midbrain (the substantia nigra and ventral tegmental area) send dense projections to the dorsal and ventral striatum (the caudate-putamen and nucleus accumbens) in the
A Double Blind , Placebo-Controlled Study of Naltrexone in the Treatment of Alcohol Dependence

The goal of this study was to assess the efficacy of a 50-mg-per-day dose of naltrexone in the maintenance treatment of alcohol-dependent patients over a 12-week treatment period. Patients were randomized to two groups. Subjects consisted of 116 male alcohol dependents who met the DSM-IV criteria for alcohol dependence and were seeking treatment. Patients received naltrexone at a dose of 50 mg per day or placebo in a double-blind placebo-controlled trial, and were treated in an outpatient clinic, offering a weekly 0.5-hour individual counseling session. Days retained in treatment were measured. Overall, 71 patients (61.2%) completed the 12week study. Completion rates by group were 79.3% for the 50 mg naltrexone group and 43.1% for the placebo group (χ = 16.01; p<0.0001). The results support the efficacy and safety of naltrexone for outpatient treatment of alcohol-dependent patients (German J Psychiatry 2002; 5(4): 85-89).
Effective Design-Based Model Selection for Definitive Screening Designs

ABSTRACT Since their introduction by Jones and Nachtsheim in 2011, definitive screening designs (DSDs) have seen application in fields as diverse as bio-manufacturing, green energy production, and laser etching. One barrier to their routine adoption for screening is due to the difficulties practitioners experience in model selection when both main effects and second-order effects are active. Jones and Nachtsheim showed that for six or more factors, DSDs project to designs in any three factors that can fit a full quadratic model. In addition, they showed that DSDs have high power for detecting all the main effects as well as one two-factor interaction or one quadratic effect as long as the true effects are much larger than the error standard deviation. However, simulation studies of model selection strategies applied to DSDs can disappoint by failing to identify the correct set of active second-order effects when there are more than a few such effects. Standard model selection strategies such as stepwise regression, all-subsets regression, and the Dantzig selector are general tools that do not make use of any structural information about the design. It seems reasonable that a modeling approach that makes use of the known structure of a designed experiment could perform better than more general purpose strategies. This article shows how to take advantage of the special structure of the DSD to obtain the most clear-cut analytical results possible.
Child and familial pathways to academic achievement and behavioral adjustment: A prospective six-year study of children with and without ADHD

This longitudinal study examined familial and child predictors of academic achievement and behavioral adjustment. Participants included 115 children with ADHD and 59 normative comparisons. Data analyses spanned three assessment waves from elementary-through secondary-school grades. We evaluated the degree to which child and familial factors present during middle school mediated relationships between childhood ADHD, subsequent academic achievement, and behavioral adjustment during high school. We found that emotional and behavioral well-being of ADHD children during middle school mediated relations between childhood ADHD and adverse academic and behavioral outcomes during high school. In addition, familial factors in middle school years predicted the behavioral adjustment of children in both the ADHD and non-ADHD groups. Academic achievement during high school was strongly associated with previous achievement levels. Our results provide support for tailoring preventive interventions to the unique needs of children with ADHD and their parents at various stages of adolescent development.
Epidemiological study on vaginal Candida glabrata isolated from pregnant women

Candida glabrata was the second most frequently occurring fungus and the dominant non-albicans species caused candidal vulvovaginitis. We used a randomly amplified polymorphic DNA method to compare genotypes of vaginal C. glabrata from pregnant women with or without clinical symptoms. The aims of our study were to define the prevalence of C. glabrata during pregnancy and identify the relationship between genotypes of C. glabrata and the clinical symptoms. A total of 50 C. glabrata strains were isolated, identified, and genotyped from 628 pregnant women. The prevalence of C. glabrata during pregnancy was 7.96% (50/628). C. glabrata was detected in 25.12% (50/199) of all Candida isolates. 17 unique genotypes were generated by RAPD and the mean SAB value of all isolates was 0.891±0.002. All results show that the genotypes of vaginal C. glabrata isolated from pregnant women were highly similar but non-identical. Compared to those of symptomatic patients in the same trimester and asymptomatic patients in different trimesters, C. glabrata isolated from the asymptomatic patients in the first trimester had more genotypical similarities. Genotypical similarities of C. glabrata were related to clinical signs and symptoms, to some degree.