Miracle-dz/UniFAR-FTUs huggingface dataset:
New Method for Fast and Accurate Binding‐site Identification and Analysis

Structure‐based drug design seeks to exploit the structure of protein‐ligand or protein‐protein binding sites, but the site is not always known at the outset. Even when the site is known, the researcher may wish to identify alternative prospective binding sites that may result in different biological effects or new class of compounds. It is also vital in lead optimization to clearly understand the degree to which known binders or docking hits satisfy or violate complementarity to the receptor. SiteMap is a new technique for identifying potential binding sites and for predicting their druggability in lead‐discovery applications and for characterizing binding sites and critically assessing prospective ligands in lead‐optimization applications. In large‐scale validation tests, SiteMap correctly identifies the known binding site in > 96% of the cases, with best results (> 98%) coming for sites that bind ligands tightly. It also accurately distinguishes between sites that bind ligands and sites that don't. In binding‐site analysis, SiteMap provides a wealth of quantitative and graphical information that can help guide efforts to modify ligand structure to enhance potency or improve physical properties. These attributes allow SiteMap to nicely complement techniques such as docking and computational lead optimization in structure‐base drug design.
Alphaproteobacterial dominance in a large mesotrophic lake (Lake Biwa, Japan)

We used fluorescence in situ hybridization to examine seasonal variation over 7 mo in the relative abundance of phylogenetic groups of bacterioplankton in the large (area 673.8 km 2 , maximum depth 104 m) mesotrophic, freshwater Lake Biwa, Japan. Alphaproteobacteria dominated the community, with relative abundances (42 ± 12% (mean ± SD, n = 40) of total prokaryote abun- dance) much higher than those in other freshwater communities described in the literature. The second most abundant groups were Actinobacteria (14 ± 9.6%) and Betaproteobacteria (12 ± 6%) followed by the Cytophaga-Flavobacteria (CF) cluster (5.8 ± 3.5%). Filament communities were less diverse, consisting of only Alphaproteobacteria (64 ± 15% (n = 44) of the total filament abundance) and the CF cluster (28 ± 16%). Although seasonal patterns were different among different phylo- genetic and morphotypic groups, Alphaproteobacteria consistently dominated the community throughout the seasons. Our data suggest that Lake Biwa differs from other lakes in some key aspects, urging further investigation of detailed taxonomic compositions and ecological features of freshwater Alphaproteobacteria.
Is there an epidemic of child or adolescent depression?

BACKGROUND Both the professional and the general media have recently published concerns about an 'epidemic' of child and adolescent depression. Reasons for this concern include (1) increases in antidepressant prescriptions, (2) retrospective recall by successive birth cohorts of adults, (3) rising adolescent suicide rates until 1990, and (4) evidence of an increase in emotional problems across three cohorts of British adolescents. METHODS Epidemiologic studies of children born between 1965 and 1996 were reviewed and a meta-analysis conducted of all studies that used structured diagnostic interviews to make formal diagnoses of depression on representative population samples of participants up to age 18. The effect of year of birth on prevalence was estimated, controlling for age, sex, sample size, taxonomy (e.g., DSM vs. ICD), measurement instrument, and time-frame of the interview (current, 3 months, 6 months, 12 months). RESULTS Twenty-six studies were identified, generating close to 60,000 observations on children born between 1965 and 1996 who had received at least one structured psychiatric interview capable of making a formal diagnosis of depression. Rates of depression showed no effect of year of birth. There was little effect of taxonomy, measurement instrument, or time-frame of interview. The overall prevalence estimates were: under 13, 2.8% (standard error (SE) . 5%); 13-18 5.6% (SE .3%); 13-18 girls: 5.9% (SE .3%); 13-18 boys: 4.6% (SE .3%). CONCLUSIONS When concurrent assessment rather than retrospective recall is used, there is no evidence for an increased prevalence of child or adolescent depression over the past 30 years. Public perception of an 'epidemic' may arise from heightened awareness of a disorder that was long under-diagnosed by clinicians.
The Dichotomy in the Preinvasive Neoplasia to Invasive Carcinoma Sequence in the Pancreas: Differential Expression of MUC1 and MUC2 Supports the Existence of Two Separate Pathways of Carcinogenesis

Emerging evidence suggests a dichotomy in the dysplasia–CIS-invasive carcinoma sequence in the pancreas. Pancreatic intraepithelial neoplasms (PanINs; small, incidental duct lesions) progress to invasive ductal adenocarcinomas (5-y survival of <15%), whereas intraductal papillary mucinous neoplasms (large, intraductal tumors with ductal dilatation) are often associated with colloid carcinoma (5-y survival of >55%). We explored the relationship of these lesions by examining the expression of MUC1 and MUC2, glycoproteins reportedly reflecting “aggressive” and “indolent” phenotypes in pancreas cancer, respectively. Immunohistochemical labeling with MUC1 (clone Ma695) and MUC2 (clone Ccp58) antibodies was performed on PanINs (n = 43), intraductal papillary mucinous neoplasms (n = 74), ductal adenocarcinomas (n = 136), and colloid carcinomas (n = 15). Fifty-four percent of the intraductal papillary mucinous neoplasms expressed MUC2, whereas none of the PanINs did. In contrast, PanINs, especially higher grade lesions, were often positive for MUC1 (61% of PanIN 3), whereas the expression of this glycoprotein was infrequent in intraductal papillary mucinous neoplasms (20%). This dichotomy was further accentuated in the invasive carcinomas with which these two preinvasive pathways are respectively associated: all colloid carcinomas were MUC2+ (100%) and MUC1− (0%), whereas the labeling pattern was the reverse for ductal adenocarcinomas: 63% were MUC1+ and only 1% were MUC2+. These results support a dichotomy in the dysplasia–CIS sequence in the pancreas. Because these two pathways often lead to different types of invasive carcinomas, this is an invaluable model for the study of carcinogenesis. The findings here also support the previous impression that MUC2 (the mucin associated with gel formation) is a marker of the “indolent” pathway (intraductal papillary mucinous neoplasm and colloid carcinoma), whereas MUC1 (the glycoprotein known to have an inhibitory role in cell–cell and cell–stroma interactions as well as in immunoresistance of tumor cells) is a marker of the “aggressive” pathway (PanIN to ductal adenocarcinoma).
Learning from “ Shadow Security : ” Why nderstanding on-ompliant ehaviors rovides the asis for ffective ecurity

Over the past decade, security researchers and practitioners have tried to understand why employees do not comply with organizational security policies and mechanisms. Past research has treated compliance as a binary decision: people comply, or they do not. From our analysis of 118 in-depth interviews with individuals (employees in a large multinational organization) about security non-compliance, a 3rd response emerges: shadow security. This describes the instances where securityconscious employees who think they cannot comply with the prescribed security policy create a more fitting alternative to the policies and mechanisms created by the organization’s official security staff. These workarounds are usually not visible to official security and higher management – hence ‘shadow security’. They may not be as secure as the ‘official’ policy would be in theory, but they reflect the best compromise staff can find between getting the job done and managing the risks that the assets they understand face. We conclude that rather than trying to ‘stamp out’ shadow security practices, organizations should learn from them: they provide a starting point ‘workable’ security: solutions that offer effective security and fit with the organization’s business, rather than impede it.
Dietary fish oil and cytokine and eicosanoid production during human immunodeficiency virus infection.

BACKGROUND Dietary fish oil (FO) has been shown to modulate the immune system. The purpose of this study was to explore the effects of FO supplementation on the production of dienoic eicosanoids and cytokines in patients with human immunodeficiency virus (HIV) infection. METHODS This was a randomized, prospective, double-blind study that included homosexual males with HIV infection. Patients were asked to consume voluntarily five food bars daily containing FO (n = 10) or safflower oil (SO) (n = 9) for 6 weeks. At baseline and week 6, plasma was obtained to measure incorporation of omega-3 fatty acids. At baseline, week 3, and week 6, measurements were made of changes in dienoic eicosanoids and cytokines from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) or spontaneously releasing cells. RESULTS In the FO group but not the SO group, there was increased incorporation of the omega-3 fatty acid docosahexaenoic acid (DHA) into the phospholipids of the fatty acids of the plasma. In the FO group, there was a significant decrease (p = .01) in 6-keto prostaglandin (PG) F1 alpha released from PBMC. There was a significant increase (p = .01) in interleukin (IL)-6 released from the PBMC in the FO group between baseline and week 3 and between week 3 and week 6. At week 6, there was significantly more IL-6 (p = .01) released from the PBMC in the FO group compared with the SO group. There was no change in CD4 cell counts by analysis of variance. CONCLUSIONS The FO-containing food bars were well tolerated and allowed incorporation of omega-3 fatty acids to occur. Despite evidence of significant metabolic effects on eicosanoid and cytokine production, widespread clinical use of FO for HIV-infected patients is not warranted without further study, particularly given the trend toward a decline in CD4 cell numbers at this dose and with this type of fish oil.
Analysis of Epstein-Barr Virus Glycoprotein B Functional Domains via Linker Insertion Mutagenesis

ABSTRACT Epstein-Barr Virus (EBV) glycoprotein B (gB) is essential for viral fusion events with epithelial and B cells. This glycoprotein has been studied extensively in other herpesvirus family members, but functional domains outside of the cytoplasmic tail have not been characterized in EBV gB. In this study, a total of 28 linker insertion mutations were generated throughout the length of gB. In general, the linker insertions did not disrupt intracellular expression and variably altered cell surface expression. Oligomerization was disrupted by insertions located between residues 561 and 620, indicating the location of a potential site of oligomer contacts between EBV gB monomers. In addition, a novel N-glycosylated form of wild-type gB was identified under nonreducing Western blot conditions that likely represents a mature form of the protein. Fusion activity was abolished in all but three variants containing mutations in the N-terminal region (gB30), within the ectodomain (gB421), and in the intracellular C-terminal domain (gB832) of the protein. Fusion activity with variants gB421 and gB832 was comparable to that of the wild type with epithelial and B cells, and only these two mutants, but not gB30, were able to complement gB-null virus and subsequently function in virus entry. The mutant gB30 exhibited a low level of fusion activity with B cells and was unable to complement gB-null virus. The mutations generated here indicate important structural domains, as well as regions important for function in fusion, within EBV gB.
5 Stereotactic Radiosurgery for Pituitary Adenomas

Stereotactic Radiosurgery (SRS) is a technology that utilizes externally generated ionizing radiation to treat (a) defined target(s) in the head or spine without the need to make an incision. The target is defined by high-resolution stereotactic imaging. It uses multiple convergent beams aimed to the target. The beams deliver a maximal dose to the target (with precision of less than 1mm), while minimizing irradiation of the surrounding tissues. The treatment is performed in a single session. The procedure requires a multidisciplinary team consisting of a neurosurgeon, radiation oncologist and medical physicist. Technologies that are used to perform SRS include linear accelerators, particle beam accelerators and multisource Cobalt 60 units. In order to enhance precision, various devices may incorporate robotics and real time digital imaging. (Stereotactic Radiosurgery Task Force AANS/CNS/ASTRO, March 20, 2006).
Angiotensin II is the mediator of the increase in hepatic angiotensinogen synthesis after bilateral nephrectomy.

The present study investigated the hypothesis that the increase in plasma angiotensinogen after nephrectomy is mediated by endogenous renin and angiotensin (ANG) II. Rats were divided into control, nephrectomy, or nephrectomy plus adrenalectomy groups. In addition, similar cohorts were divided as just mentioned and then given either atenolol (selective beta 1-adrenoceptor inhibitor that prevents renin release) or Dup-753 [ANG II (AT1) receptor antagonist]. The plasma angiotensinogen levels increase approximately fivefold after 24 h in nephrectomized rats. Pretreatment with atenolol blunted this increase. A significant reduction was observed 4 h (P < 0.05) and 8 h (P < 0.005) after surgery. Dup-753 nearly abolished the increase in angiotensinogen plasma levels. After pretreatment with Dup-753, significantly higher angiotensinogen levels (P < 0.005) were found only after 24 h. Nephrectomy plus adrenalectomy also blunted the rise in plasma angiotensinogen. A significant increase in angiotensinogen plasma levels could only be observed after 8 h (P < 0.005) and 12 h (P < 0.005) but not after 24 h. Atenolol further reduced this increase. After atenolol pretreatment, significantly higher angiotensinogen levels could only be observed after 12 h (P < 0.05). Dup-753 completely abolished the increase of plasma angiotensinogen after nephrectomy plus adrenalectomy. In anesthetized control rats at time 0 the plasma ANG I levels were 0.7 nM. Pretreatment with atenolol decreased the ANG I values by 30%, whereas Dup-753 caused a sixfold increase in plasma ANG I levels in the control rats at time 0. (ABSTRACT TRUNCATED AT 250 WORDS)
On Observation of Time-Delay Systems With Unknown Inputs

Causal and non-causal observability are discussed in this technical note for nonlinear time-delay systems with unknown inputs. Using the theory of non-commutative rings and the algebraic framework introduced by Xia , the nonlinear time-delay system is transformed into a suitable canonical form to solve the problem. A necessary and sufficient condition is given to guarantee the existence of a change of coordinates leading to such a form.
Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel complexes with ISA‐like properties

Kv4 pore‐forming subunits are the principal constituents of the voltage‐gated K+ channel underlying somatodendritic subthreshold A‐type currents (ISA) in neurones. Two structurally distinct types of Kv4 channel modulators, Kv channel‐interacting proteins (KChIPs) and dipeptidyl‐peptidase‐like proteins (DPLs: DPP6 or DPPX, DPP10 or DPPY), enhance surface expression and modify functional properties. Since KChIP and DPL distributions overlap in the brain, we investigated the potential coassembly of Kv4.2, KChIP3 and DPL proteins, and the contribution of DPLs to ternary complex properties. Immunoprecipitation results show that KChIP3 and DPP10 associate simultaneously with Kv4.2 proteins in rat brain as well as heterologously expressing Xenopus oocytes, indicating Kv4.2 + KChIP3 + DPP10 multiprotein complexes. Consistent with ternary complex formation, coexpression of Kv4.2, KChIP3 and DPP10 in oocytes and CHO cells results in current waveforms distinct from the arithmetic sum of Kv4.2 + KChIP3 and Kv4.2 + DPP10 currents. Furthermore, the Kv4.2 + KChIP3 + DPP10 channels recover from inactivation very rapidly (τrec∼18–26 ms), closely matching that of native ISA and significantly faster than the recovery of Kv4.2 + KChIP3 or Kv4.2 + DPP10 channels. For comparison, identical triple coexpression experiments were performed using DPP6 variants. While most results are similar, the Kv4.2 + KChIP3 + DPP6 channels exhibit inactivation that slows with increasing membrane potential, resulting in inactivation slower than that of Kv4.2 + KChIP3 + DPP10 channels at positive voltages. In conclusion, the native neuronal subthreshold A‐type channel is probably a macromolecular complex formed from Kv4 and a combination of both KChIP and DPL proteins, with the precise composition of channel α and auxiliary subunits underlying tissue and regional variability in ISA properties.
A Novel CBCD Approach Using MPEG-7 Motion Activity Descriptors

Motion features contribute significant information about a video content. This paper highlights a novel CBCD (Content-Based Copy Detection) approach, by incorporating several motion activity features. First, we extract both temporal and spatial motion features to describe overall activity of a video sequence. Second, we combine these features in a feasible manner, to generate robust video fingerprints. Third, clustering based pruned search is utilized for similarity matching instead of direct searching of video fingerprints. The proposed system is tested on TRECVID-2007 data set and the results demonstrate the effectiveness of the proposed system against several transformations such as random noise, fast forward, pattern insertion, cropping and picture-inside-picture.
Geometric barycenters and their application to radar training data selection/target detection

This paper deals with the problem of covariance matrix estimation for radar signal processing applications. We propose and analyze a class of estimators which do not require any knowledge about the probability distribution of the sample support and exploit the characteristics of the positive definite matrix space. Any estimator of the class is associated with a suitable distance in the considered space and is defined as the geometric barycenter of some basic covariance matrix estimates obtained from the available secondary data set.
Medicare Part D Coverage Gap: Race, Gender, and Cost-Related Medication Nonadherence

This study examined whether the Medicare Part D coverage gap directly and indirectly affects the relationship between race, gender, and cost-related nonadherence (CRN). Using a nationally representative sample (N = 1,157), this study found that racial disparities in CRN existed under Medicare Part D. However, reaching the coverage gap mediated differences in CRN between older Blacks and Whites. The coverage gap was associated with CRN and poorer health and lower income were associated with CRN after accounting for coverage gap status. Findings highlight the need to help vulnerable populations avoid CRN and for greater consideration of racial inequities in future policy decisions.
Power Amplifier Integrated With Bandpass Filter for Long Term Evolution Application

This letter presents a high-power amplifier (PA) matched by bandpass filter (BPF) for long term evolution (LTE) applications. The phase shift of the BPF is found to retain ±90° at the working frequency. It can be employed as the output impedance transformer which transforms 50 Ω to the desired maximum power point. By using this method, the high-PA integrated with the BPF avoids extreme wide line and obtain three functions which could boost the radio signal, select the working frequency band and eliminate the harmonics at the same time. The system dimensions are consequently reduced as the following BPF after PA is omitted. A high-PA matched by BPF working at 2.6 GHz is designed. The analysis is given and the measured results and comparisons are presented. The good agreement confirms the validity of the proposed method.
Periodontitis: A risk for delivery of premature labor and low birth weight infants

Periodontitis is a destructive inflammatory disease of the supporting tissues of the teeth and is caused by specific microorganisms or a group of specific microorganisms. Association of periodontal infection with organ systems like cardiovascular system, endocrine system, reproductive system, and respiratory system makes periodontal infection a complex multiphase disease. Inflamed periodontal tissues produce significant amounts of pro-inflammatory cytokines, mainly interleukin 1 beta (IL-1β), IL-6, prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF-α), which may have systemic effects on the host. Low birth weight, defined as birth weight less than 2500 g, continues to be a significant public health issue in both developed and developing countries. Research suggests that the bacteria that cause inflammation in the gums can actually get into the bloodstream and target the fetus, potentially leading to premature labor and low birth weight (PLBW) babies. One reasonable mechanism for this is the deleterious effect of endotoxin released from gram-negative bacteria responsible for periodontal disease. Hence, periodontal disease appears to be an independent risk factor for PLBW and there is a need to expand preventive measures for pregnant women in coordination with the gynecological and dental professions.
Comparative evaluation of radiometric tryptic soy broth versus radiometric tryptic soy broth with 10% sucrose for detection of bacteremia and fungemia in pediatric patients

We compared BACTEC radiometric blood culture media with (8B) and without (6B) 10% sucrose for the detection of bacteremia and fungemia in pediatric patients at four university teaching hospitals that used identical methods for obtaining and processing specimens. Overall, the yields of microorganisms from 5,714 blood culture sets were no different in the two media, although a trend was noted favoring 6B for the detection of pneumococci. Speed of detection of positive results was faster in the 6B than in the 8B medium (P less than 0.05), largely due to the faster detection of Staphylococcus aureus in the 6B medium. We conclude that, overall, with pediatric patients the hypertonic 8B radiometric medium has no advantage and that it possibly has a modest disadvantage, compared with isotonic 6B radiometric medium.