Miracle-dz/UniFAR-FTUs huggingface dataset:
Interdomain side‐chain interactions in human γD crystallin influencing folding and stability

Human γD crystallin (HγD‐Crys) is a two domain, β‐sheet eye lens protein that must remain soluble throughout life for lens transparency. Single amino acid substitutions of HγD‐Crys are associated with juvenile‐onset cataracts. Features of the interface between the two domains conserved among γ‐crystallins are a central six‐residue hydrophobic cluster, and two pairs of interacting residues flanking the cluster. In HγD‐Crys these pairs are Gln54/Gln143 and Arg79/Met147. We previously reported contributions of the hydrophobic cluster residues to protein stability. In this study alanine substitutions of the flanking residue pairs were constructed and analyzed. Equilibrium unfolding/refolding experiments at 37°C revealed a plateau in the unfolding/refolding transitions, suggesting population of a partially folded intermediate with a folded C‐terminal domain (C‐td) and unfolded N‐terminal domain (N‐td). The N‐td was destabilized by substituting residues from both domains. In contrast, the C‐td was not significantly affected by substitutions of either domain. Refolding rates of the N‐td were significantly decreased for mutants of either domain. In contrast, refolding rates of the C‐td were similar to wild type for mutants of either domain. Therefore, domain interface residues of the folded C‐td probably nucleate refolding of the N‐td. We suggest that these residues stabilize the native state by shielding the central hydrophobic cluster from solvent. Glutamine and methionine side chains are among the residues covalently damaged in aged and cataractous lenses. Such damage may generate partially unfolded, aggregation‐ prone conformations of HγD‐Crys that could be significant in cataract.
Formalization Description and Instance Research on Particle Swarm Optimization Algorithm

Formalization description of particle swarm optimization algorithm is proposed based on the collectivity mode framework of swarm intelligence in this paper. As a specific case, a modified particle swarm optimization algorithm is brought forward in formalization description mode on the basis of defining the optimum information broadcasting mode, in which broadcasting scope of the optimum information is provided with logical grouped-and-delayed characteristic and dynamic spreading scope characteristic. The algorithm? s effectiveness is proved by computer simulation results.
The Evolving Internet: Applications and Network Service Infrastructure

This article has three goals. It begins by reviewing the current state of the Internet as a data transport system and some of its emerging problems. Then it discusses two major research initiatives -Internet 2 and the Next Generation Internet (NGI) program- and some of the new network-level services that may first see substantial deployment in these new research testbeds. The article concludes with a few speculations about future changes to the Internet as a data transport system.
α1-Antitrypsin Portland Inhibits Processing of Precursors Mediated by Proprotein Convertases Primarily within the Constitutive Secretory Pathway*

We studied the extent of cellular inhibitory activity of α1-antitrypsin Portland (α1-PDX), a potent inhibitor of proprotein convertases of the subtilisin/kexin type. We compared the inhibitory effects of α1-PDX on the intracellular processing of two model precursors (pro-7B2 and POMC) mediated by six of the seven known mammalian convertases, namely furin, PC1, PC2, PACE4, PC5-A, PC5-B, and PC7. The substrates selected were pro7B2, a precursor cleaved within the trans-Golgi network (TGN), and pro-opiomelanocortin, which is processed in the TGN and secretory granules. Biosynthetic analyses were performed using either vaccinia virus expression in BSC40, GH4C1, and AtT20 cells, or stable transfectants of α1-PDX in AtT20 cells. Results revealed that α1-PDX inhibits processing of these precursors primarily within the constitutive secretory pathway and that α1-PDX is cleaved into a shorter form by some convertases. Evidence is presented demonstrating that in contrast to the full-length α1-PDX (64 kDa), the cleaved (56 kDa) secreted product does not significantly inhibit furin activity in vitro. Cellular expression of α1-PDX results in modified contents of mature secretory granules with increased levels of partially processed products. Biosynthetic and immunocytochemical analyses of AtT20/α1-PDX cells demonstrated that α1-PDX is primarily localized within the TGN, and that a small proportion enters secretory granules where it is mostly stored as the cleaved product.
Undetectable hepatitis C virus RNA at week 4 as predictor of sustained virological response in HIV patients with chronic hepatitis C

Background: Low baseline serum hepatitis C virus (HCV)-RNA and clearance of viraemia at week 4 with pegylated interferon (pegIFN) plus ribavirin therapy predict sustained virological response (SVR) and enable a shorter duration of therapy in patients with chronic hepatitis C. It is unclear whether this applies to HIV/HCV-co-infected patients. Patients and methods: In the Peginterferon Ribavirin ESpaña COinfection (PRESCO) trial, 389 co-infected patients received pegIFN-α2a 180 μg/week plus ribavirin 1000–1200 mg/day. Patients with HCV-2/3 were treated for 6 or 12 months, whereas patients with HCV-1/4 were treated for 12 or 18 months. For each genotype, baseline HCV-RNA and rapid virological response (RVR), defined as under 50 IU/ml HCV-RNA at week 4, were evaluated as predictors of SVR in an ‘on-treatment’ analysis. Results: Overall, SVR was achieved by 193 patients (49.6%), 68/191 (35.6%) with genotype 1, 110/152 (72.4%) with genotypes 2/3 and 15/46 (32.6%) with genotype 4. RVR was the best predictor of SVR regardless of HCV genotype. Only for HCV-1 patients, baseline HCV-RNA less than 500 000 IU/ml was also associated with SVR. In HCV-3 patients RVR had a positive predictive value (PPV) for SVR of 90%, with treatment for 24 or 48 weeks. The PPV of SVR for patients with RVR was 69% for HCV-1 and 83% for HCV-4. Conclusion: Undetectable HCV-RNA at week 4 is the best predictor of curing chronic hepatitis C in HCV/HIV-co-infected patients. In HCV-1 patients, baseline HCV-RNA also predicts response. HIV patients with HCV-3 and RVR may permit shortening therapy duration to only 24 weeks of pegIFN plus 1000–1200 mg ribavirin.
Polarization Dependent Transmission through a Symmetrical Metallic Grating on Low-Absorption Polymer Substrates

Abstract-A planar structured wire-grid like Cu/polythene/Cu device is designed and demonstrated to control coherent broadband terahertz transmission. The addition of periodic copper corrugation on each side of a polythene wafer allows surface plasmon polaritons localized in the core layer interface to control the intensity and phase shifting of transmitted wave. A significant enhancement and extinction of the terahertz (THz) transmission can be achieved through variation of polarization angle of surface plasmons in the parallel and perpendicular directions.
The Human Cytomegalovirus US10 Gene Product Delays Trafficking of Major Histocompatibility Complex Class I Molecules

ABSTRACT Human cytomegalovirus (HCMV) US10 encodes a glycoprotein that binds to major histocompatibility complex (MHC) class I heavy chains. While expression of US10 delays the normal trafficking of MHC class I molecules out of the endoplasmic reticulum, US10 does not obviously facilitate or inhibit the action of two other HCMV-encoded MHC class I binding proteins, US2 and US11.
Best feature selection for emotional speaker verification in i-vector representation

This paper is dedicated to the gender-dependent text-independent speaker verification from Slovak emotional speech. To investigate the best speaker verification performance different features were extracted in front-end processing, namely MFCC (Mel-Frequency Cepstral Coefficients), LPC (Linear Prediction Coefficients) and LPCC (Linear Prediction Cepstral Coefficients), and their mapping into low-dimensional vector of fixed length was performed following the principles of i-vector method. In evaluation process of i-vectors scoring following Mahalanobis distance metric was employed.
The detection of small simulated field defects using multifocal VEPs

Introduction: The multifocal visual‐evoked potential (mfVEP) has been widely investigated in the study of diseases of the visual system. However, the sensitivity of the mfVEP in objective detection of field defects has not been determined. This study investigates the variation of the mfVEP responses whilst simulating field defects by using different sizes of mask on the stimulus pattern.
The effects of youth training on risk behavior: the role of non-cognitive skills

AbstractThis paper uses unique experimental data from a youth training program in the Favelas, Brazil, to examine whether youth training programs can prevent treatment recipients from engaging in risk behavior—i.e., cigarettes, alcohol, and hard drug utilization, as well as witnessing or being a victim of violent crime. Although the program was successful in increasing income, we find that it only improved risk behavior of the treated individuals with higher levels of socio-emotional skills. JEL Classification: O11, O22, O17
Local feature fitting active contour for segmenting vessels in angiograms

An active contour model for vascular segmentation has been proposed, by defining a new, local, feature fitting, energy function. A vesselness filter is applied to the image in a directional Hessian-based framework. The filter output, as a feature, expresses the degree of the correspondence of each pixel to the vessel structure. By using intensity information obtained from local regions, the proposed model is able to solve the problem of intensity inhomogeneity in images. In addition, by introducing this feature into the fitting process, the model exhibits greater accuracy when compared to existing models. Experimental results from synthetic images and coronary X-ray angiograms verify the desirable performance of the proposed model.
Identification and distance detection for ultrasonic sensor by correlation method

Abstract This paper presents a method for identification and distance detection for ultrasonic sensors of indoor mobile robot by using correlation scheme. The transmitted signal is identified by correlation between known model patterns and the patterned signal from transmitters and this scheme is useful when multiple sensors are involved. Distance detection by correlation is shown to be more accurate than conventional threshold method.
Quantifying antigenic relationships among the Lyssaviruses 2 Running title 3 Quantifying Lyssavirus antigenic relationships

Horton, D.L. , 1,2,3* ; McElhinney, L.M. , 1,7 ; Marston, D.A. , 1 ; Wood, J.L. N. , 2 ; Russell, 6 C.A. , 3,6 ; Lewis, N. , 2,3 ; Kuzmin, I.V. , 4 ; Fouchier, R.A.M., 5 ;Osterhaus, A.D.M.E. 5 ; 7 Fooks, A.R. 1,7 ; Smith, D. J. 3,5,6 8 1 Rabies and Wildlife Zoonoses, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, 9 Surrey KT15 3NB, UK. 10 2 Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, Cambridge, CB2 11 1DQ, UK. 12 3 Department of Zoology, Cambridge University, Downing Street, Cambridge, CB2 3EJ, UK. 13 4 Centers for Disease Control and Prevention, Division of Viral and Rickettsial Diseases, 1600 Clifton 14 Road, MSG-33, Atlanta, GA 30333, USA. 15 5 Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, 16 Netherlands 17 6 Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA 18 7 The National Centre for Zoonosis Research, University of Liverpool, Leahurst, Chester High Road, 19 Neston, CH64 7TE, UK 20 21
Expression of DARC, CXCR3 and CCR5 in giant cell arteritis.

OBJECTIVES Leucocyte infiltration is the hallmark of vasculitis, chemokines being mainly responsible for leucocyte migration into inflamed tissues. The objective was to evaluate the local expression of chemokines and chemokine receptors in biopsies of patients with giant cell arteritis (GCA) compared with arteries from patients with polymyalgia rheumatica (PMR). We studied the expression of CCR5, CXCR3 and that of the Duffy antigen/receptor of chemokine (DARC), a chemokine internalizing receptor (interceptor), in parallel to the expression of the CCR5 ligand RANTES/CCL5. METHODS Paraffin-embedded tissue sections from six patients with GCA and five patients with PMR were available for immunohistological analysis of chemokine receptor expression. RANTES/CCL5 mRNA was detected in tissue sections by in situ hybridization. RESULTS In patients with biopsy-proven giant cell arteritis, CCR5 and CXCR3 were highly expressed by infiltrating leucocytes in involved tissue sections. Predominant clustering of CCR5+ and CXCR3+ leucocytes was found in the adventitia and was co-localized with the expression of CCL5/RANTES mRNA. Interestingly, we found marked expression of DARC on adventitial high endothelial venules in vasculitis lesions of patients with GCA, while in arteries from patients with PMR DARC was only expressed on a low number of vessels with flat lining endothelium. CONCLUSIONS The co-localization of infiltrating CCR5+ and CXCR3+ leucocytes together with CCL5/RANTES and DARC in vasculitis lesions suggests a role for these chemokine receptors in leucocyte infiltration, possibly supported by DARC-mediated vascular presentation of chemokines.
Formulation and evaluation of anti-rheumatic dexibuprofen transdermal patches: a quality-by-design approach

Abstract Dexibuprofen (DXIBN) transdermal patches were formulated using various concentrations of selected polymeric excipients (matrix material; ethyl cellulose and polyvinylpyrrolidone, plasticizer (di-N-butyl phthalate), and a conventional permeation enhancer (almond oil)). Initial patch formulations were evaluated for their physiochemical properties (thickness, moisture uptake, final moisture content, and DXIBN content). Also, impact of patch components on resulting tensile strength and in vitro permeation were used to predict an optimal patch formulation using a quality-by-design (QbD) approach, which was subsequently evaluated and further compared with a commercial oral tablet dosage form for in vitro and in vivo release (rabbit model). Initially formulated patches demonstrated uniform thickness (0.44 ± 0.02 cm), relatively low moisture uptake (7.87 ± 1.11 w/w %), and highly acceptable drug loading values (100.0 ± 0.026%). The tensile strength of patches increased significantly with matrix polymer concentration and to a lesser degree with increase in plasticizer and permeation enhancer content, although these affected the permeation of DXIBN. Predicted properties (tensile strength and DXIBN steady-state flux) for the QbD-optimized formulation were in close agreement to experimental results. The QbD optimal patch formulation behavior differed significantly from the commercial tablet formulation in vivo. Such model-based predictions (QbD approach) will reduce cost and time in formulation development sciences.
Differences by race, sex and age in the clinical and immunologic features of recently diagnosed systemic lupus erythematosus patients in the southeastern United States

We examined the prevalence of clinical and immunologic features of systemic lupus erythematosus (SLE) by race, sex and age in a population-based study of 265 SLE patients. Patients ful” lled the American College of Rheumatology classi” cation criteria. The median time between diagnosis and study enrollment was 13 months. The clinical and hematologic data were limited to occurrences up to 6 months after the diagnosis date, as documented in medical records. We used sera collected at study enrollment from 244 (92%) patients for serologic testing of autoantibodies. The associations between clinical and immunological features of SLE and age, sex and race were examined using logistic regression. The effect of each of these variables was examined adjusting for the other two demographic factors. Mean age at diagnosis was 6 years younger among African-Americans and other minorities compared with white patients (P < 0.01). Discoid lupus, proteinuria, anti-Sm and anti-RNP autoantibodieswere more commonly seen in African-American patients, with odds ratios higher than 3.0. Photosensitivity and mucosal ulcers were noted less often in African-American patients. Proteinuria, leukopenia, lymphopenia and thrombocytopenia were approximately three times more common in men compared with women. The prevalence of oral or nasal ulcers and antiDNA autoantibodies declined with age. The extent to which the differences we observed re‘ ect genetic or environmental in‘ uences on the disease process should be investigated.
Deep learning based recommender systems

In parallel with the rapid development of prospective systems in the last 20 years, many methods have been applied to this field. One of them is the deep learning networks that have attracted the interest of researchers in recent years. The DBN (Deep Belief Network), which trains one layer at a time greedily, uses unsupervised learning for each layer and is composed of RBMs (Restricted Boltzman Machine), has become a turning point in this area. In this study, the deep learning method is applied to the recommender system problem. The Python-based deep learning library, Keras, is used and the existing learning algorithms are compared.
Can you snooze your way to an ‘A’? Exploring the complex relationship between sleep, autonomic activity, wellbeing and performance in medical students

Objective: Medical training brings with it multiple stressors, including demanding workloads in highly competitive environments, with well-documented impact on psychiatric morbidity. This study evaluated the impact of sleep-related factors on psychological wellbeing, cognitive task performance and academic standing in medical students. Methods: A total of 59 undergraduate medical students took part in this cross-sectional study over two consecutive days. Participants responded to questionnaires about their physical and psychological health, sleep, functioning and academic performance at the initial visit. Participants then wore an ambulatory bioharness overnight (to derive heart rate variability measures), before returning to complete a computerised battery of cognitive tasks. A sleep diary was completed for the next 7 days. Results: Poor sleep quality in the month preceding assessment correlated with psychological distress (p < 0.001) and reduced nocturnal heart rate variability (p = 0.007). Psychological distress also correlated with reduced nocturnal heart rate variability (p = 0.031) and less refreshing sleep during the monitoring week (p < 0.001), but not with sleep timing parameters. A greater increase in heart rate variability during the transition from awake to sleep significantly predicted better spontaneous cognitive performance (p = 0.021). Better academic standing was predicted by consistently short, less refreshing sleep (all p < 0.001), along with earlier bedtimes (p = 0.004) and greater psychological wellbeing (p = 0.009). Conclusion: Unrefreshing, short-duration sleep and psychological distress are prevalent in medical students during university training and were associated with reduced nocturnal parasympathetic autonomic activity. Achieving higher academic grades was associated with high psychological wellbeing despite consistently short, unrefreshing sleep. The long-term repercussions of such sleep behaviours on later professional functioning remain unclear, warranting further research.
Guidelines for the use of RNA purification kits.

INTRODUCTION With the proliferation of researchers investigating various aspects of RNA biology has come a corresponding proliferation of commercially available kits for RNA purification. Some of these kits have specialized uses and applications, and it is not always possible to simply mix and match the different protocols. Although the instructions are often written with a minimum of specifics concerning the chemical basis for the separation characteristics that the kits use, the competent researcher will want to understand these important features. Unfortunately, commercial sources work hard to hide the specifics of their methods. Fortunately, patent documents are publicly available, and the government mandates material safety data disclosures of the composition of at least those components that represent a threat to environmental health and safety. Thus, it is possible to infer many aspects of such "proprietary" materials, which in most cases are only slightly and unimportantly modified from published techniques. We do not describe in detail the specific steps involved in the use of particular kits; they are detailed in the literature that comes with each kit and their components (e.g., proprietary buffers). Instead, we detail some advantages and disadvantages of using RNA purification kits.
Proceedings of preparing for a significant Central United States earthquake-Science needs of the response and recovery community

6 Introduction . 7 Discussion . 7 Shaking Intensity Versus Distance . 7 Potential Economic Impact of Soil Liquefaction . 8 Shaking Intensity Varies According to Underlying Geology . 8 Likely Impacts of Most Probable Quake . 8 Planning Aspects . 11 Regional and National Economic Impacts . 12 Conclusions . 12 References . 13 Earthquake Hazards (Timing/Reoccurrence/Probability of an Event) . 14 Conference Abstract . 14 Post-Conference Paper . 14 Earthquake Hazard and Recurrence in the New Madrid Region . 14 Abstract . 14.14 Introduction . 14 Earthquake Hazard . 14 Earthquake Ground Motions . 14 The Earthquake Source . 15 Earthquake Recurrence . 16 Paleoseismology and Large Infrequent Earthquakes . 16 Earthquake Recurrence from the Instrumental Catalog . 17
Optimization of train speed curve based on ATO tracking control strategy

How to reduce the energy consumption of urban rail transit system is always the focus of attention. The automatic train operation(ATO) system operates trains between successive stations by controlling the speed automatically, which is very important for the train energy saving operation. The traditional ATO recommended speed curve optimization research is based on line information, train information and control objectives to generate the optimal recommended speed curve, which does not take the influence ATO tracking control strategy taken on the practical driving strategy into account. In this paper, the recommended speed curve optimization and ATO tracking control strategy are considered together. On the basis of using the dynamic programming to optimize the recommended speed curve of the train, a method based on the existing ATO tracking control strategy for the recommended speed curve optimization is given. The method can effectively reduce the energy consumption under the condition that the running time is acceptable.
Social and therapeutic horticulture: evidence and messages from research

This literature review presents a detailed analysis of over 100 texts relating to the outcomes and effectiveness of horticulture and gardening in a number of different therapeutic settings and with different client groups. It will be invaluable to anyone interested in demonstrating the benefits of social and therapeutic horticulture, as well as those interested in understanding the background and development of this growing field. This literature review represents the first part Growing Together, the first detailed study of horticulture and gardening projects across the UK. The Growing Together study is a partnership between Thrive and Loughborough University and has been funded by the Big Lottery Fund.