Miracle-dz/UniFAR-FTUs huggingface dataset:
Determinants of the Src Homology Domain 3-Like Fold

ABSTRACT In eukaryotes, the Src homology domain 3 (SH3) is a very important motif in signal transduction. SH3 domains recognize poly-proline-rich peptides and are involved in protein-protein interactions. Until now, the existence of SH3 domains has not been demonstrated in prokaryotes. However, the structure of the C-terminal domain of DtxR clearly shows that the fold of this domain is very similar to that of the SH3 domain. In addition, there is evidence that the C-terminal domain of DtxR binds to poly-proline-rich regions. Other bacterial proteins have domains that are structurally similar to the SH3 domain but whose functions are unknown or differ from that of the SH3 domain. The observed similarities between the structures of the C-terminal domain of DtxR and the SH3 domain constitute a perfect system to gain insight into their function and information about their evolution. Our results show that the C-terminal domain of DtxR shares a number of conserved key hydrophobic positions not recognizable from sequence comparison that might be responsible for the integrity of the SH3-like fold. Structural alignment of an ensemble of such domains from unrelated proteins shows a common structural core that seems to be conserved despite the lack of sequence similarity. This core constitutes the minimal requirements of protein architecture for the SH3-like fold.
MOS memory with double-layer high-κ tunnel oxide Al2O3/HfO2 and ZnO charge trapping layer

In this work, the effect of using a double layer of high-κ tunnel oxides Al2O3/HfO2 instead of a single layer Al2O3 in MOS memory with ZnO charge trapping layer is studied. A memory effect due to charging in the ZnO layer is observed using high frequency C-V measurements. The shift of the threshold voltage (Vt) obtained from the hysteresis measurements at 10/-10 V program/erase voltage is around 3.3 V with single layer tunnel oxide while 7 V with the double layer tunnel oxide with same total oxide thickness. In addition, the memory structures show long retention times (>10 years) which make them promising for applications in non-volatile memory devices. Moreover, the results highlight that tunnel band engineering can be used to further reduce the operating voltage and equivalent oxide thickness of future memory devices without sacrificing the memory performance.
Antibody-based diagnostic for 'refractory' periodontitis.

OBJECTIVE About 10-15% of US adults are 'refractory' to therapy for chronic periodontitis. Recently, studies suggest that these patients have elevated lysine decarboxylase activity in the sulcular microbiota. The aim of this study was to determine whether an elevated IgG antibody response to lysine decarboxylase, alone or with antibody to other bacterial antigens and baseline clinical measurements, would predict 'refractory' patients with high accuracy. METHODS Chronic periodontitis patients were treated using scaling and root planing (SRP) followed by maintenance SRP and 3-monthly re-examinations. If there was a loss of mean full mouth attachment or more than three sites appeared with > 2.5 mm new loss within a year, the subjects were re-treated (modified Widman flap surgery and systemically administered tetracycline). If attachment loss as above recurred, the subjects were 'refractory'. Baseline clinical measurements and specific antibody responses were used in a logistic regression model to predict 'refractory' subjects. RESULTS Antibody to a peptide portion of lysine decarboxylase (HKL-Ab) and baseline bleeding on probing (BOP) prevalence measurements predicted attachment loss 3 months after initial therapy [pIAL = loss (0) or gain (1)]. IgG antibody contents to a purified antigen from Actinomyces spp. (A-Ab) and streptococcal d-alanyl glycerol lipoteichoic acid (S-Ab) were related in 'refractory' patients (R2 = 0.37, p < 0.01). From the regression equation, the relationship between the antibodies was defined as linear (pLA/S-Ab = 0) or non-linear pLA/S-Ab = 1). Using pLA/S-Ab, pIAL and age, a logistic regression equation was derived from 48 of the patients. Of 59 subjects, 37 had 2-4 mm attachment loss and were assigned as 'refractory' or successfully treated with 86% accuracy. CONCLUSION HKL-Ab facilitated an accurate prediction of therapeutic outcome in subjects with moderate periodontitis.
Large‐scale affordable Panleucogated CD4+ testing with proactive internal and external quality assessment: In support of the South African national comprehensive care, treatment and management programme for HIV and AIDS

In order to expand the treatment of human immunodeficiency virus‐1 (HIV) infected patients in Africa, millions will require cost‐effective CD4 counts. Supporting laboratories therefore, need to move away from crisis management and haphazard practices to organized pathology services. The authors reviewed the performance of the simplified single platform (SP) PanLeucogated (PLG) CD4 methodology, introduced into 52 laboratories across the South African National Health Laboratory Service (SA‐NHLS), with a proactive approach to training, internal quality control (IQC), and external quality assessment (EQA).
Title Binding of translationally controlled tumour protein to theN-terminal domain of HDM 2 is inhibited by Nutlin-3

Translationally Controlled Tumour Protein (TCTP), a highly conserved protein present in all eukaryotic organisms, has a number of intracellular and extracellular functions including an anti-apoptotic role. TCTP was recently shown to interact with both p53 and HDM2, inhibiting auto-ubiquitination of the latter and thereby promoting p53 degradation. In this study, we further investigated the interaction between TCTP and HDM2, mapping the reciprocal binding sites of TCTP and HDM2. TCTP primarily interacts with the N-terminal, p53-binding region of HDM2 through its highly basic domain 2. Furthermore, we discovered that Nutlin-3, a small molecule known to promote apoptosis and cell cycle arrest by blocking binding between HDM2 and p53, has a similar inhibitory effect on the interaction of HDM2 and TCTP. This result may provide an additional explanation of how Nutlin-derived compounds currently in clinical trials function to promote apoptosis in cancer cells. Citation: Funston G, Goh W, Wei SJ, Tng QS, Brown C, et al. (2012) Binding of Translationally Controlled Tumour Protein to the N-Terminal Domain of HDM2 Is Inhibited by Nutlin-3. PLoS ONE 7(8): e42642. doi:10.1371/journal.pone. 0042642 Editor: Carl G. Maki, Rush University Medical Center, United States of America Received May 15, 2012; Accepted July 10, 2012; Published August 13, 2012 Copyright: 2012 Funston et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the Agency for Science, Technology and Research (Singapore). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: CV is a PLoS ONE Academic Editor. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials. * E-mail: fghadessy@p53Lab.a-star.edu. sg . These authors contributed equally to this work.
Opinions on Psychotherapy: An Enquiry

This enquiry was prompted by a discussion on training in psychotherapy which took place at the Troon Conference on the Teaching of Psychiatry (Ingram, 1963). We felt that more precise information was required about what is meant by the term psychotherapy, which methods are in use and what opinions are held by psychotherapists in training. This information could be of value in assessing the workload of psychiatrists and in deciding what training might be given to psychiatrists and medical students. It was therefore decided to seek the opinions of Scottish psychiatrists on some aspects of their current practice in psychotherapy.
Bottom-Up versus Top-Down Induction of Sleep by Zolpidem Acting on Histaminergic and Neocortex Neurons

Zolpidem, a GABAA receptor-positive modulator, is the gold-standard drug for treating insomnia. Zolpidem prolongs IPSCs to decrease sleep latency and increase sleep time, effects that depend on α2 and/or α3 subunit-containing receptors. Compared with natural NREM sleep, zolpidem also decreases the EEG power, an effect that depends on α1 subunit-containing receptors, and which may make zolpidem-induced sleep less optimal. In this paper, we investigate whether zolpidem needs to potentiate only particular GABAergic pathways to induce sleep without reducing EEG power. Mice with a knock-in F77I mutation in the GABAA receptor γ2 subunit gene are zolpidem-insensitive. Using these mice, GABAA receptors in the frontal motor neocortex and hypothalamic (tuberomammillary nucleus) histaminergic-neurons of γ2I77 mice were made selectively sensitive to zolpidem by genetically swapping the γ2I77 subunits with γ2F77 subunits. When histamine neurons were made selectively zolpidem-sensitive, systemic administration of zolpidem shortened sleep latency and increased sleep time. But in contrast to the effect of zolpidem on wild-type mice, the power in the EEG spectra of NREM sleep was not decreased, suggesting that these EEG power-reducing effects of zolpidem do not depend on reduced histamine release. Selective potentiation of GABAA receptors in the frontal cortex by systemic zolpidem administration also reduced sleep latency, but less so than for histamine neurons. These results could help with the design of new sedatives that induce a more natural sleep. SIGNIFICANCE STATEMENT Many people who find it hard to get to sleep take sedatives. Zolpidem (Ambien) is the most widely prescribed “sleeping pill. ” It makes the inhibitory neurotransmitter GABA work better at its receptors throughout the brain. The sleep induced by zolpidem does not resemble natural sleep because it produces a lower power in the brain waves that occur while we are sleeping. We show using mouse genetics that zolpidem only needs to work on specific parts and cell types of the brain, including histamine neurons in the hypothalamus, to induce sleep but without reducing the power of the sleep. This knowledge could help in the design of sleeping pills that induce a more natural sleep.
A randomised controlled study of mindfulness meditation versus relaxation therapy in the management of tinnitus

Abstract Objective: Psychotherapeutic interventions have been adopted effectively in the management of tinnitus for a long time. This study compared mindfulness meditation and relaxation therapy for management of tinnitus. Methods: In this randomised controlled trial, patients were recruited for five sessions of mindfulness meditation or five sessions of relaxation therapy. Patients’ responses were evaluated using the Tinnitus Reaction Questionnaire as a primary outcome measure, and the Hospital Anxiety and Depression Scale, visual analogue scale and a health status indicator as secondary outcome measures. Results: A total of 86 patients were recruited. Thirty-four patients completed mindfulness meditation and 27 patients completed relaxation therapy. Statistically significant improvement was seen in all outcome measures except the health status indicator in both treatment groups. The change in treatment scores was greater in the mindfulness meditation group than in the relaxation therapy group. Conclusion: This study suggests that although both mindfulness meditation and relaxation therapy are effective in the management of tinnitus, mindfulness meditation is superior to relaxation therapy.
Matrilin-2, a Large, Oligomeric Matrix Protein, Is Expressed by a Great Variety of Cells and Forms Fibrillar Networks*

Matrilin-2 is a member of the protein superfamily with von Willebrand factor type A-like modules. Mouse matrilin-2 cDNA fragments were expressed in 293-EBNA cells, and the protein was purified, characterized, and used to immunize rabbits. The affinity-purified antiserum detects matrilin-2 in dense and loose connective tissue structures, subepithelial connective tissue of the skin and digestive tract, specialized cartilages, and blood vessel walls. In situ hybridization of 35S-labeled riboprobes localizes the matrilin-2 mRNA to fibroblasts of dermis, tendon, ligaments, perichondrium, and periosteum; connective tissue elements in the heart; smooth muscle cells; and epithelia and loose connective tissue cells of the alimentary canal and respiratory tract. RNA blot hybridization and immunoblotting revealed both matrilin-2 mRNA and protein in cultures of a variety of cell types, confirming the tissue distribution. Alternative splicing affects a module unique for matrilin-2 in all of the above RNA sources. SDS-polyacrylamide gel electrophoresis and electron microscopy reveals matrilin-2 from tissue extracts and cell line cultures as a mixture of mono-, di-, tri-, and tetramers. Matrilin-2 is substituted with N-linked oligosaccharides but not with glycosaminoglycans. Because of other, yet unidentified, cell-type dependent posttranslational modifications, the monomer is heterogeneous in size. Immunofluorescence showed that matrilin-2 functions by forming an extracellular, filamentous network.
Enabling wireless power transfer though a metal encased handheld device

Wireless power transfer through a metal object is a major obstacle for the conventionally available tightly coupled inductive system. In this paper, we demonstrate that a metal encased mobile device is enabled for efficient wireless charging using a loosely coupled resonant system. To facilitate this approach, three coils are designed and distributed on a metal phone case and they are tuned for resonance at 6.78MHz. With electromagnetic analysis of the coil geometry, a prototype is fabricated by machining an aluminum. Measurement results show that 8W can be delivered to the load on a regular AFA (AirFuel Alliance)-resonant compatible charger. In practice, using all three coils is optional and a designer may use only one coil for the metal cover design.
Complex PTSD: A syndrome in survivors of prolonged and repeated trauma.

This paper reviews the evidence for the existence of a complex form of post-traumatic disorder in survivors of prolonged, repeated trauma. This syndrome is currently under consideration for inclusion in DSM-IV under the name of DESNOS (Disorders of Extreme Stress Not Otherwise Specified). The current diagnostic formulation of PTSD derives primarily from observations of survivors of relatively circumscribed traumatic events. This formulation fails to capture the protean sequelae of prolonged, repeated trauma. In contrast to a single traumatic event, prolonged, repeated trauma can occur only where the victim is in a state of captivity, under the control of the perpetrator. The psychological impact of subordination to coercive control has many common features, whether it occurs within the public sphere of politics or within the private sphere of sexual and domestic relations.
Prospective Study of the Association Between Neurobehavior Disinhibition and Peer Environment on Illegal Drug Use in Boys and Girls

Background: Individual and contextual factors jointly participate in the onset and progression of substance abuse; however, the pattern of their relationship in males and females has not been systematically studied. Objectives: Male and female children and adolescents were compared to determine the relative influence of individual susceptibility (neurobehavior disinhibition or ND) and social environment (deviancy in peers) on use of illegal drugs. Methods: Boys (N = 380) and girls (N = 127) were prospectively tracked from age 10–12 to age 16 to delineate the role of ND and peer deviancy on use of illegal drugs. Results: Girls exhibited lower ND scores than boys in childhood and were less inclined to affiliate with deviant peers. These differences were reduced or disappeared by mid-adolescence. In boys only, peer deviancy in childhood mediated the association between ND and illegal drug use at age 16. In both genders, peer deviancy in mid-adolescence mediated ND and substance abuse at age 16. Conclusions: Individual and contextual risk factors promoting substance abuse are more salient at a younger age in boys compared to girls. Scientific Significance: These results point to the need for earlier screening and intervention for boys.
Cu(In,Ga)Se$_{\bf 2}$ Solar Cells With Varying Na Content Prepared on Nominally Alkali-Free Glass Substrates

In this paper, Cu(In,Ga)Se2 (CIGS) thin-film solar cells are prepared on nominally alkali-free glass substrates using an in-line CIGS growth process. As compared with, for example, borosilicate glass or quartz, the glass is engineered to have similar thermal expansion coefficient as soda-lime glass (SLG) but with alkali content close to zero. Na is incorporated in the CIGS material using an ex-situ deposited NaF precursor layer evaporated onto the Mo back contact. Several thicknesses of the NaF layer were tested. The results show that there is a process window, between 15 and 22.5 nm NaF, where the solar cell conversion efficiency is comparable with or exceeding that of SLG references. The effect of an NaF layer that is too thin on the solar cell parameters was mainly lowering the open-circuit voltage, which points to a lower effective dopant concentration in the CIGS layer and is also consistent with presented C - V measurements and modeling results. For excessively thick NaF layers, delamination of the CIGS layer occurred. Additional measurements, such as scanning electron microscopy (SEM), secondary ion mass spectrometry, capacitance-voltage analysis (C - V), time-resolved photoluminescence (TRPL), external quantum efficiency (EQE), current-voltage analysis (J-V), and modeling, are presented, and the results are discussed.
A Knowledge-Based Approach to Social Sensors for Environmentally-Related Problems

Social media can serve to contribute to situation awareness, which involves the perception and comprehension of the reality around us, so that future actions can be projected. For example, Twitter can be used as a real-time channel of communication to report on environmentally-related problems. The goal of this paper is to describe a knowledge-based system that is able to detect such problems, so that a protocol of action can be developed. The evaluation of the system demonstrated that our symbolic approach to problem detection can outperform supervised classification methods.
Wideband beam and null steering using a rectangular array of planar monopoles

This article presents the design of a wideband rectangular array of planar monopoles, which is able to steer its beam and nulls over a wide frequency band using real-valued weights. These weights can be realized in practice by amplifiers or attenuators leading to a low cost development of a wideband array antenna with beam and null steering capability. The weights are determined by applying an inverse discrete Fourier transform to an assumed radiation pattern. This wideband beam and null forming concept is verified by full electromagnetic simulations which take into account mutual coupling effects between the array elements
A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein*

Background: Rabies virus expresses five isoforms of P protein, which undergo nucleocytoplasmic trafficking important to roles as antagonists of interferon-mediated immunity. Results: P isoform trafficking is mediated by a novel module containing co-regulated overlapping nuclear localization and export signals. Conclusion: P isoform nuclear localization involves a novel trafficking module. Significance: A novel molecular switch regulating trafficking, important to a viral interferon antagonist, is identified. Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1–P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3–P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection.
Treatment with Methimazole in a 3-Year-Old Male with Thyroid Hormone Resistance

Background: Thyroid hormone resistance syndromes are disorders in which there is decreased end-organ responsiveness to thyroid hormone. Patients typically present with elevated levels of thyroxine and triiodothyronine with a normal or increased serum thyroid-stimulating hormone concentration. Clinical features are variable, and there are no guidelines regarding treatment. Patient: The patient was noted to have tachycardia at 6 months of age. He had persistently elevated free thyroxine and normal/mildly elevated thyroid-stimulating hormone for the first 2 years of life. At age 2 years, he was noted to have sinus tachycardia, a mildly enlarged thyroid, hyperactive behavior, subtle developmental delay, and poor weight gain. The patient has a previously described de novo mutation in the thyroid hormone receptor-β gene. Intervention and Outcomes: He was started on methimazole (0.3–0.5 mg/kg/day) at age 3 years to treat his symptoms. With medication, weight gain, sleep, behavior, and tachycardia improved. Linear growth has remained appropriate for age. Heart rate is in the upper normal range and his thyroid has become more enlarged. Conclusions: Methimazole has improved thyrotoxic symptoms in a 3-year-old male with thyroid hormone resistance. The use of methimazole should be considered in certain patients.
Recognizing Natural Emotions in Speech, Having Two Classes

Emotion recognition is a useful way to filter important information, especially when it comes to situations where statistics are kept to track ones performance during work time, such as for workers in a call centre (for example, you might want to record a call when a customer sounds angry, so you can track the patience of an employee). However, there is little research conducted on how emotion recognition methods behave in practice, compared to the work that has been done using data from actors. This paper emphasizes on the input data (sound samples), requiring them to be natural instead of acted. It shows that training and testing on the same datasets yield high accuracy rates (with accuracy rates on acted data around 90%, and accuracy rates on natural data between 60 – 70%). When cross trained-tested with the acted set as training data and the natural set as testing data, there is not much difference from randomly labelling the samples. However, if the natural set is used as training data and the acted set as testing data, the classifiers SMO and AdaBoostM1 yield very high accuracy rates (78.6% and 74.2% respectively) and the Bayesian Network classifier only classifies the samples as „anger/frustration‟.