Miracle-dz/UniFAR-FTUs huggingface dataset:
Binding of antifusion peptides with HIVgp41 from molecular dynamics simulations: Quantitative correlation with experiment

Peptides based on C‐terminal regions of the human immunodeficiency virus (HIV) viral protein gp41 represent an important new class of antiviral therapeutics called peptide fusion inhibitors. In this study, computational methods were used to model the binding of six peptides that contain residues that pack into a conserved hydrophobic pocket on HIVgp41, an attractive target site for the development of small molecule inhibitors. Free energies of binding were computed using molecular mechanics Generalized Born surface area (MM‐GBSA) methods from molecular dynamics (MD) simulations, which employed either explicit (TIP3P) or continuum Generalized Born (GB) water models and strong correlations between experimental and computational affinities were obtained in both cases. Energy decomposition of the TIP3P‐MD results (r2 = 0.75) reveals that variation in experimental affinity is highly correlated with changes in intermolecular van der Waals energies (ΔEvdw) on both a local (residue‐based, r2 = 0.94) and global (peptide‐based, r2 = 0.84) scale. The results show that differential association of C‐peptides with HIVgp41 is driven solely by changes within the conserved pocket supporting the hypothesis that this region is an important drug target site. Such strong agreement with experiment is notable given the large size of the ligands (34 amino‐acids) relative to the small range of experimental affinities (2 kcal/mol) and demonstrates good sensitivity of this computational method for simulating peptide fusion inhibitors. Finally, inspection of simulation trajectories identified a highly populated π‐type hydrogen bond, which formed between Gln575 on the receptor and the aromatic ring of peptide ligand Phe631, which could have important implications for drug design. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Circular Pseudo-Point Approximations for Scaling Gaussian Processes

We introduce a new approach for performing accurate and computationally efficient posterior inference for Gaussian Process regression problems that exploits the combination of pseudo-point approximations and approximately circulant covariance structure. We argue mathematically that the new technique has substantially lower asymptotic complexity than traditional pseudo-point approximations and demonstrate empirically that it returns results that are very close to those obtained using exact inference.
RFID and beyond - growing your business through real world awareness

PART I: Real World Awareness in Business 1. Business Navigation and Real World Awareness 2. How Real World Awareness Will Change Your Business 3. The Technologies of Real World Awareness 4. Business Process Design and Optimization 5. Implementing Real World Awareness 6. People, Privacy, Politics PART II: Experts in Real World Awareness 7. Mastering the Legal Challenges 8. The Impact of RFID on Supply Chain Efficiency 9. Exploding Edges and Potential for Disruption 10. The X Internet Unleashes Real World Awareness Services Revolution Index
Treatment‐resistant depression: recent developments and future directions

A significant proportion of patients with major depressive disorder (MDD) fail to achieve remission with standard antidepressant therapies, even when optimally delivered. These patients are classified as treatment-resistant depression (TRD), which is distinguished from “difficult-to-treat” depression,[1] defined as depression treated under circumstances that precludes the optimal delivery of a potentially beneficial treatment (e.g., subtherapeutic dosing, intolerable side effects, poor adherence, etc.) TRD is also distinguished from severe depression, as some patients with milder depressive symptoms are markedly treatment resistant, while others with profound, acute depressive symptoms are quite treatment responsive. Defining the boundaries of TRD is critical from a clinical, research, and public health perspective, as drug and device manufacturers seek new regulatory approvals for numerous indications in the TRD spectrum. This article reviews recent developments in TRD, with a focus on classification methods used for regulatory clinical trials; treatments currently approved in the US for TRD; how classification schemes and regulatory rules have limited understanding of their scope of effectiveness; and what changes are needed in research approaches to facilitate novel therapeutic discovery.
Multiple RF-carrier Generation Using the Wavelength-dependent Stokes Shift and Selective Amplification of Stimulated Brillouin Scattering

We present an optical method that can simultaneously generate multiple RF-carriers. The generated RF-carriers meet the requirements of channel separation in fixed wireless services. The proposed method utilizes the wavelength-dependent Stokes shift and selective amplification of stimulated Brillouin scattering in an optical fiber. Four RF-carriers at 10.851, 10.831, 10.811, and 10.791 GHz, which have the narrow linewidth and the 20-MHz separation, are generated using four optical sources spaced 2.78 nm apart.
Immunolocalization of a lipase-like protein in the reproductive apparatus of female Phlebotomus papatasi, at various stages of the gonotrophic cycle

Abstract In female phlebotomine sandflies, little is known about the reproductive accessory glands that presumably contribute to egg production and/or oviposition. The main protein secreted in the accessory glands of female Phlebotomus papatasi was recently characterised as a lipase-like protein, the first to be found in the female accessory glands of any insect. This protein, named PhpaLIP (for Phlebotomus papatasi lipase), has now been detected and localized in the reproductive tissues of female P. papatasi, at different stages of the gonotrophic cycle, using a polyclonal anti-PhpaLIP serum and both confocal scanning laser and immuno-electron microscopy. PhpaLIP appears to be always present in the accessory glands (with a secretory peak shortly before oviposition) but was also detected in the follicle cells of the ovarioles, within the developing vitelline envelope, and in the oviducts. The results are discussed in relation to the functions that PhpaLIP could have during the gonotrophic cycle, in the various reproductive structures of female P. papatasi.
The Efficacy and Cost of Prophylactic and Periprocedural Antibiotics in Patients with External Ventricular Drains

OBJECTIVEProphylactic antibiotics are routinely administered to patients with external ventricular drains (EVDs); however, no conclusive evidence supports this practice. This study compared the efficacy and cost of prophylactic and periprocedural antibiotics in patients with EVDs. METHODSWe reviewed the charts of 308 patients who had an EVD in place for 3 or more days between January 1996 and June 1997. Patients with EVDs placed for shunt infections or meningitis were excluded. A standard protocol was used to insert and monitor EVDs. Catheters were left in place as long as clinically indicated and changed only if they malfunctioned. Cerebrospinal fluid cultures were obtained twice weekly. Prophylactic antibiotics were used at the discretion of the attending neurosurgeon. Patients were divided into two groups: Group A comprised 209 patients who received prophylactic antibiotics for the duration of the EVD (intravenously administered cefuroxime, 1.5 g every 8 h); Group B comprised 99 patients who received only periprocedural antibiotics (intravenously administered cefuroxime, 1.5 g every 8 h, three or less doses). RESULTSAlthough there were significantly more males in Group A than in Group B, the two groups were otherwise well matched, with no significant differences in age, indications, or duration of EVD placement. The overall rate of ventriculitis was 3.9%. The infection rates for Group A (3.8%) and Group B (4.0%) were almost identical. CONCLUSIONProphylactic antibiotics did not significantly reduce the rate of ventriculitis in patients with EVDs, and they may select for resistant organisms. Discontinuing the use of prophylactic antibiotics for EVDs at the authors’ institution would save approximately $80,000 per year in direct drug costs.
Muscle Activity of Lower Extremities for Normal Adults According to the Type of Chair and Posture During Sit-to-stand Movement

The purpose of this study is to investigate the effect of sit to stand movement on the muscle activity of lower extremities muscles by the different type of chair and posture. Total 52 healthy adult between 19 and 26 were selected as subject for the study. The muscle activities of vastus lateralis, rectus femoris, vastus medialis, tibialis anterior and gastrocnemius by the different types of chair during sit to stand movement were measured by using surface electromyography WEMG. Sit to stand movement was performed by the different types of chair. For both fixed and wheeled chairs, rectus femoris and vastus lateralis showed a statistically significant difference (p<.05) when standing, while vastus medialis, rectus femoris, and vastus lateralis showed a statistically significant difference when sitting (p<.05). Comparison of standing and sitting positions revealed that all muscle types except gastrocnemius showed a statistically significant difference. This study suggests that it can be useful for providing fundamental data regarding the muscle activation of lower limbs according to chair type.
Phagocytosis of mycobacteria by U937 cells: a rapid method for monitoring uptake and separating phagocytosed and free bacteria by magnetic beads

J. WHYTE, A.D.G. ROBERTS, K.A. MORLEY, R.J. SHARP and P.D. MARSH.2000. A human‐derived monocytic cell line (U937) was induced to phagocytose Mycobacterium phlei by the addition of phorbol myristate acetate (PMA) to the culture medium for 50–60 h. Cells not treated with PMA were unable to phagocytose M. phlei. Magnetic beads enabled a rapid and highly efficient separation of phagocytosed and free bacteria to be achieved, an approach which is particularly useful if colony plating is used to enumerate bacterial survival within phagocytic cells. Fluorescence‐activated cell sorting (FACS) analysis showed that 98% of U937 cells contained viable bacteria after 3 h.
Inhibition of autophagy at a late stage enhances imatinib‐induced cytotoxicity in human malignant glioma cells

Malignant gliomas are common primary tumors of the central nervous system. The prognosis of patients with malignant glioma is poor in spite of current intensive therapy and thus novel therapeutic modalities are necessary. Imatinib mesylate, a tyrosine kinase inhibitor, is effective in the therapy of tumors including leukemias but not as a monotherapy for malignant glioma. Recently, it is thought that the adequate modulation of autophagy can enhance efficacy of anticancer therapy. The outcome of autophagy manipulation, however, seems to depend on the autophagy initiator, the combined stimuli, the extent of cellular damage and the type of cells, and it is not yet fully understood how we should modulate autophagy to augment efficacy of each anticancer therapy. In this study, we examined the effect of imatinib with or without different types of autophagy inhibitors on human malignant glioma cells. Imatinib inhibited the viability of U87‐MG and U373‐MG cells in a dose dependent manner and caused nonapoptotic autophagic cell death. Suppression of imatinib‐induced autophagy by 3‐methyladenine or small interfering RNA against Atg5, which inhibit autophagy at an early stage, attenuated the imatinib‐induced cytotoxicity. In contrast, inhibition of autophagy at a late stage by bafilomycin A1 or RTA 203 enhanced imatinib‐induced cytotoxicity through the induction of apoptosis following mitochondrial disruption. Our findings suggest that therapeutic efficiency of imatinib for malignant glioma may be augmented by inhibition of autophagy at a late stage, and that appropriate modulation of autophagy may sensitize tumor cells to anticancer therapy. © 2008 Wiley‐Liss, Inc.
Expression and Purification of GnT15 an N-acetylglucosamine Binding Protein from Dictyostelium Discoideum in E.coli

Glycosyltransferases play an essential role in protein glycosylation, localization and function. In Dictyostelium discoideum (D.discoideum), four GlcNAc transferases genes, gnt12, gnt13, gnt14 and gnt15 were identified by an in silico approach based on their similarity to mammalian GlcNAc transferase. The glycosyltransferase activities of these gene products were unknown. In this study, we expressed D.discoideum GlcNAc transferase (DdGnT15) in E.coli and its biochemical function was explored. The phylogenetic alignment showed DdGnT15 had higher similarity with hs β3GnT1 among the 9 human β3GnTs. The expressed DdGnT15 protein was purified by Ni-NTA column and confirmed by Western blot. The DdGnT15 showed no GlcNAc transferase activity with pyridylaminated lacto-N-neotetraose as substrate under in vitro conditions. The carbohydrate binding activity of DdGnT15 was measured by incubating with affinity matrix containing immobilized carbohydrates. DdGnT15 bound to a matrix containing immobilized N-acetylglucosamine, but not to other carbohydrates. These results helped to conclude that DdGnT15 is a carbohydrate binding protein with binding specificity similar to that of wheat germ agglutinin. We hypothesize that DdGnT15 is the first identified D.discoideum GlcNAc lectin.
Identification of T cell lymphoma tumor antigens on human T cell lines

All human T lymphoblast cell lines have been derived from subjects with leukemia secondary to thymic lymphoblastic lymphoma, a T cell malignacy, suggesting that such lines represent established cultures of neoplastic T cells. Based on this observation, we prepared rabbit antisera to T cell line HSB‐2, removed reactivity for histocompatibility antigens and normal T cells by absorption with autocthonous B cell line CCRF‐SB and normal thymocytes, and tested the absorbed antisera by complement‐dependent cytotoxicity against a panel of normal and malignant cells.
Femoral Condyle Geometry in the Normal and Varus Knee

Femoral condyle geometry was evaluated in 30 normal and 30 varus knees using magnetic resonance imaging. In the sagittal view, the distal part of the medial condyle was deformed in the varus knees, but there was no significant difference in the posterior part of the medial condyle between the normal and varus knees. In the transverse view, the transepicondylar axis(a reliable rotational landmark) showed approximately 6° external rotation relative to the posterior condylar axis in the varus knees and the normal knees. The results of this study suggest that no hypoplasia exists at the posterior part of the medial condyle in varus knees. In addition, the posterior condylar axis may be a reliable rotational landmark but is in relative internal rotation in varus knees when total knee arthroplasty is performed.
Modulation of Retinoic Acid Receptor-related Orphan Receptor α and γ Activity by 7-Oxygenated Sterol Ligands*

The retinoic acid receptor-related orphan receptors α and γ (RORα (NR1F1) and RORγ (NR1F3)) are orphan nuclear receptors and perform critical roles in regulation of development, metabolism, and immune function. Cholesterol and cholesterol sulfate have been suggested to be RORα ligands, but the physiological significance is unclear. To date, no endogenous RORγ ligands have been described. Here, we demonstrate that 7-oxygenated sterols function as high affinity ligands for both RORα and RORγ by directly binding to their ligand-binding domains (Ki ∼20 nm), modulating coactivator binding, and suppressing the transcriptional activity of the receptors. One of the 7-oxygenated sterols, 7α-hydroxycholesterol (7α-OHC), serves as a key intermediate in bile acid metabolism, and we show that 7α-OHC modulates the expression of ROR target genes, including Glc-6-Pase and phosphoenolpyruvate carboxykinase, in an ROR-dependent manner. Furthermore, glucose output from hepatocytes is suppressed by 7α-OHC functioning as an RORα/γ ligand. Thus, RORα and RORγ are ligand-regulated members of the NR superfamily and may serve as sensors for 7-oxygenated sterols.
Postural Balance Following Aerobic Fatigue Tests: A Longitudinal Study Among Young Athletes

ABSTRACT General fatigue can cause aggravation of postural balance, with increased risk for injuries. The present longitudinal study aimed to evaluate the postural balance of young athletes following field aerobic tests throughout 1 year of training. Thirty children from a sports center in Nazareth, participating in a 3 times/week training program (specific to basketball, soccer, or athletic training), were assessed. Postural balance parameters were taken before, immediately after, and 10 min after a 20 m shuttle-run aerobic test, at 3 time points during 1 training year (Start/Y, Mid/Y, and End/Y). Fitness improved at the Mid/Y and End/Y compared to Start/Y. Postural balance significantly deteriorated immediately after the aerobic test and improved significantly in the 10-min testing in all 3 time points, with significant deterioration in the End/Y compared with the Start/Y. In conclusions, postural balance deteriorates immediately after aerobic exercises, and at the end of the year. To better practice drills related to postural balance and possibly to prevent injuries, it is best for young athletes to properly rest immediately following aerobic exercises and to practice postural balance mainly at the beginning and at the middle of the training year.
Theoretical Risk and Prevention Model for Secondary Health Conditions and Mortality After SCI: 15 Years of Research.

BACKGROUND To successfully prevent secondary health conditions (SHCs) and promote longevity after spinal cord injury (SCI), we must first understand the risk factors precipitating their occurrence and develop strategies to address these risk factors. Conceptual models may aid in identifying the nature of SHCs and guide research, clinical practice, and the development of prevention strategies. OBJECTIVE Our purpose is to review and refine an existing theoretical risk and prevention model (TRPM) as a means of classifying risk and protective factors for SHCs and mortality after SCI and for identifying points of intervention. METHODS We describe conceptual work within the field of SCI research and SHCs, including a description of the TRPM, a review of research using the TRPM, and conceptual enhancements to the TRPM based on previous research. CONCLUSIONS The enhanced TRPM directs research to the timing and chronicity of the SHCs and their relationship with overall health and physiologic decline. Future research should identify differences in the nature of SHCs, the extent to which they relate to risk and protective factors, and the degree to which they may be prevented with appropriate research-based strategies.
Analysis of censored and incomplete survival data using flowgraph models

Multi‐state stochastic models are widely used to model stages of disease progression in survival analysis. This paper develops flowgraph models for data analysis in survival analysis. We illustrate these methods using data from a study of diabetic retinopathy consisting of 277 subjects with insulin‐dependent (type I) diabetes mellitus (IDDM). These data were collected at the Eye‐Kidney Clinic of the Barbara Davis Center for Childhood Diabetes at the University of Colorado Health Sciences Center. Copyright © 2002 John Wiley & Sons, Ltd.
Comparative analysis of on-chip transmission line de-embedding techniques

Formal comparative analysis is presented of three known de-embedding and characteristic impedance estimation techniques for on-chip transmission lines, used after probe-tip calibration. Somewhat counterintuitively, experience accumulated in the field seems to suggest that the apparently most simplistic of the three gives much better results than the other two, more "accurate-looking" techniques. The reason, however, never seems to have been explained clearly. This paper attempts to explain why and suggests some new alternative techniques.
A Systematic Review of Technology-assisted Self-Management Interventions for Chronic Pain: Looking Across Treatment Modalities

Objectives:The use of technology to provide chronic pain self-management interventions has increased in the recent years. Individual studies have primarily focused on a single technology-assisted modality and direct comparisons of different technology-assisted modalities are rare. Thus, little is known about the relative strengths and weaknesses of each technology-assisted modality. Materials and Methods:This article is a systematic review of technology-assisted self-management interventions for chronic nonheadache, noncancer pain in adults. We examined 3 treatment modalities: telephone, interactive voice response, and Internet. Electronic searches of OVID MEDLINE, OVID PsychINFO, and the Cochrane Database of Systematic Reviews were conducted. Forty-four articles including 9890 participants were reviewed. Results:Across modalities, the existing evidence suggests that technology-assisted psychological interventions are efficacious for improving self-management of chronic pain in adults. All modalities have been shown to provide benefit and no clearly superior modality has emerged. The primary gaps in the literature are lack of in-person comparison groups, lack of direct comparison among technology-assisted modalities, and heterogeneity of methods and interventions that limit comparability across studies and modalities. Discussion:Future trials should focus on direct comparisons of technology-assisted interventions with in-person treatment and head to head comparisons of different technology-assisted modalities. Additional areas of focus include quantifying the cost of technology-assisted interventions, examining the effect of treatment “dose” on outcomes, and establishing guidelines for developing treatments for the technology-assisted environment.
Secreted Aspartic Proteases as Virulence Factors of Candida Species

Abstract Candida infections have emerged as a significant medical problem during the last few decades. Among the different virulence traits of C. albicans, secreted proteolytic activity has been intensively investigated. Pathogenesis of the various forms of candidiasis was shown to be associated with the differential and temporal regulation of the expression of genes coding for secreted aspartic proteases (Sap). These enzymes act as cytolysins in macrophages after phagocytosis of Candida, are present in tissue penetration and are also involved in adherence to epithelial cells. Since the introduction of new antiretroviral therapeutics such as HIV protease inhibitors, oropharyngeal candidiasis is less often observed in AIDS patients. Different HIV aspartic protease inhibitors were able to inhibit the C. albicans Saps involved in adherence. The lower rates of oropharyngeal candidiasis observed in individuals receiving antiretroviral combination therapy could reflect not only an improvement in the immune system but also direct inhibition of Candida Saps by HIV protease inhibitors. Therefore, the development of specific aspartic protease inhibitors might be of interest for the inhibition of candidiasis.
A Study on Intrusion Detection using Data Mining Techniques

In the present world huge amounts of data are stored and transferred from one location to another. The data when transferred or stored is primed exposed to attack. Although various techniques or applications are available to protect data, loopholes exist. Thus to analyze data and to determine various kind of attack data mining techniques have emerged to make it less vulnerable. Anomaly detection uses these data mining techniques to detect the surprising behavior hidden within data increasing the chances of being intruded or attacked. Various hybrid approaches have also been made in order to detect known and unknown attacks more accurately. This paper reviews various data mining techniques for anomaly detection to provide better understanding among the existing techniques that may help interested researchers to work future in this