Miracle-dz/UniFAR-FTUs huggingface dataset:
ConFunc - functional annotation in the twilight zone

MOTIVATION The success of genome sequencing has resulted in many protein sequences without functional annotation. We present ConFunc, an automated Gene Ontology (GO)-based protein function prediction approach, which uses conserved residues to generate sequence profiles to infer function. ConFunc split sets of sequences identified by PSI-BLAST into sub-alignments according to their GO annotations. Conserved residues are identified for each GO term sub-alignment for which a position specific scoring matrix is generated. This combination of steps produces a set of feature (GO annotation) derived profiles from which protein function is predicted. RESULTS We assess the ability of ConFunc, BLAST and PSI-BLAST to predict protein function in the twilight zone of sequence similarity. ConFunc significantly outperforms BLAST & PSI-BLAST obtaining levels of recall and precision that are not obtained by either method and maximum precision 24% greater than BLAST. Further for a large test set of sequences with homologues of low sequence identity, at high levels of presicision, ConFunc obtains recall six times greater than BLAST. These results demonstrate the potential for ConFunc to form part of an automated genomics annotation pipeline. AVAILABILITY http://www.sbg. bio.ic. ac.uk/confunc
An efficient method for opportunistic beamforming with one bit feedback

It is recently shown that the opportunistic beamforming through multiple orthonormal random beamformers (ORBF), results in the optimal scaling law of sum-capacity in a multi-antenna broadcast channel when the number of system users tends to infinity. In this paper we propose a new and efficient method for decreasing the feedback amount required in the ORBF method. In our method, the required feedback reduces to 1 bit per user by partitioning the users in the system and using an optimal predetermined threshold. We evaluate a lower bound of the average sum-rate throughput of the proposed method. Our computer simulations show that the proposed scheme outperforms the proposed method in [6] which requires the same amount of feedback.
Role of Intense Affects in Predicting Short-term Risk for Suicidal Behavior: A Prospective Study

We examined the utility of the Affective States Questionnaire (ASQ) in predicting acute risk for suicidal behavior. Subjects at a VHA Medical Center were interviewed using the ASQ and again 3 months later when their suicidal behaviors over that period were examined. The ASQ had a sensitivity of 60% for predicting suicidal behavior over the follow-up period, and specificity of 74%. The false positive rate was relatively low for a sample not highly selected for suicide risk and utilizing a short period of 3 months for suicidal behavior. Subgroups combining the ASQ with disability level or a diagnosis of substance abuse greatly reduced the percentage of false positives. The ASQ is able to improve significantly our ability to predict acute risk of suicidal behavior in clinical psychiatric populations.
An empirical test of the performance of intelligence and the prospects for organizational reforms

ABSTRACT The occurrence of strategic surprises has led to the development of organizational reforms intended to prevent future intelligence failures. The limited effectiveness of such reforms conforms to a perspective that holds intelligence to be beset by inherent difficulties, such as ambiguous information, enemy deception, and human psychology, which make recurring intelligence failures inevitable. If this perspective is correct, then all functions of intelligence should be distinctly unreliable regardless of implemented reforms. I test this perspective through a comparison of the performance of military capabilities and tactical intelligence capabilities, in terms of their influence on battlefield outcomes. While tactical intelligence is susceptible to the inherent difficulties common to all functions of intelligence, it is less susceptible to the bureaucratic difficulties that most reforms, aimed at preventing strategic intelligence failures, are intended to address. I find that relatively strong tactical intelligence capabilities significantly improve battlefield effectiveness. However, the improvement associated with tactical intelligence capabilities is also significantly more inconsistent when compared to the corresponding improvement associated with military capabilities. Even when evaluating a function of intelligence less susceptible to bureaucratic difficulties, intelligence is still distinctly inconsistent in performance, suggesting that organizational reforms have only a limited ability to prevent future intelligence failures.
Nerve Fiber Ingrowth Into Scar Tissue Formed Following Nucleus Pulposus Extrusion in the Rabbit Anular-Puncture Disc Degeneration Model: Effects of Depth of Puncture

Study Design. In vivo histologic study of nerve ingrowth in the rabbit anular-puncture disc degeneration model. Objective. To examine innervation of intervertebral discs and surrounding tissues in the rabbit anular-puncture model with various magnitudes of injury. Summary of Background Data. A rabbit anular-puncture model of disc degeneration was recently established. However, to our knowledge, the neuropathologic changes in the degenerated disc and surrounding tissues in this model have not been examined. Methods. Anular punctures with an 18-gauge needle at depths of 1 and 5-mm were randomly performed at the L2–L3 or L4–L5 discs in New Zealand white rabbits (n = 16; 3.0–3.5 kg). The degree of disc degeneration was followed radiographically, and was further evaluated by magnetic resonance imaging and histology at sacrifice 4 or 12 weeks after the puncture. To identify nerve ingrowth into the discs, the L2–L3 to L4–L5 discs were immunostained with an antibody against protein gene product 9.5, a general marker for nerve fibers. Results. Significant decreases in disc height and signal intensity in magnetic resonance imaging were observed only in the 5-mm punctured discs (P < 0.05). In all the discs, including nonpunctured control discs, protein gene product 9.5-immunoreactive fibers were only occasionally observed in the outermost part of the anulus fibrosus. In the 5-mm punctured discs, nucleus pulposus tissues were extruded, and scar tissues formed outside the discs. No nerve ingrowth into the needle track lesion at the anular puncture site was observed. However, protein gene product 9.5-immunoreactive fibers were observed in scar tissues on the surface of the puncture site. This finding was more evident in the 5-mm than in the 1-mm punctured discs (P < 0.05). Conclusions. This study indicates that in the rabbit anular-puncture disc degeneration model, disc degeneration associated with a higher nerve growth into the scar tissue was more evident when induced by a 5-mm than a 1-mm puncture. Although nerve ingrowth was observed in the extruded disc tissue, nerve ingrowth into the outer anulus, which has been reported in patients with discogenic pain, was not observed during the short observation period in this disc degeneration model. The limitation in assessing pain by behavior analysis or histologic evaluation of nerve ingrowth should be considered. Further studies to identify a surrogate marker of pain should be encouraged.
Computationally‐predicted CB1 cannabinoid receptor mutants show distinct patterns of salt‐bridges that correlate with their level of constitutive activity reflected in G protein coupling levels, thermal stability, and ligand binding

The cannabinoid receptor 1 (CB1), a member of the class A G‐protein‐coupled receptor (GPCR) family, possesses an observable level of constitutive activity. Its activation mechanism, however, has yet to be elucidated. Previously we discovered dramatic changes in CB1 activity due to single mutations; T3.46A, which made the receptor inactive, and T3.46I and L3.43A, which made it essentially fully constitutively active. Our subsequent prediction of the structures of these mutant receptors indicated that these changes in activity are explained in terms of the pattern of salt‐bridges in the receptor region involving transmembrane domains 2, 3, 5, and 6. Here we identified key salt‐bridges, R2.37 + D6.30 and D2.63 + K3.28, critical for CB1 inactive and active states, respectively, and generated new mutant receptors that we predicted would change CB1 activity by either precluding or promoting these interactions. We find that breaking the R2.37 + D6.30 salt‐bridge resulted in substantial increase in G‐protein coupling activity and reduced thermal stability relative to the wild‐type reflecting the changes in constitutive activity from inactive to active. In contrast, breaking the D2.63 + K3.28 salt‐bridge produced the opposite profile suggesting this interaction is critical for the receptor activation. Thus, we demonstrate an excellent correlation with the predicted pattern of key salt‐bridges and experimental levels of activity and conformational flexibility. These results are also consistent with the extended ternary complex model with respect to shifts in agonist and inverse agonist affinity and provide a powerful framework for understanding the molecular basis for the multiple stages of CB1 activation and that of other GPCRs in general. Proteins 2013; 81:1304–1317. © 2013 Wiley Periodicals, Inc.
The potential for intraspecific horizontal gene exchange by natural genetic transformation: sexual isolation among genomovars of Pseudomonas stutzeri.

The potential for natural genetic transformation among the seven genomovars (gvs) of Pseudomonas stutzeri was investigated. Of the 12 strains originating from a variety of environments, six strains (50%) from five gvs were competent for DNA uptake (Rif(R) marker). The transformation frequencies varied over more than three orders of magnitude. With three highly transformable strains (ATCC 17587, ATCC 17641, JM300) from two gvs and all other strains as DNA donors, sexual isolation from other pseudomonad species (Pseudomonas alcaligenes, Pseudomonas mendocina) and also from other P. stutzeri gvs was observed (i.e. heterogamic transformation was reduced). For ATCC 17587 (gv 2) and ATCC 17641 (gv 8), heterogamic transformation was up to two and three orders of magnitude lower with other P. stutzeri gv and the other species employed, respectively, than in homogamic transformations. Interestingly, whereas with ATCC 17587 and ATCC 17641 heterogamic transformation with donors of the same gv was as high as homogamic transformation, JM300 (gv 8) was sexually isolated from its nearest relative (ATCC 17641). Also, sexual isolation of JM300 from other P. stutzeri gvs was most pronounced among the recipients tested, in some cases reaching the highest levels found with the other species as DNA donors (reduction of heterogamic transformation by 4000-fold). Results obtained here from nucleotide sequence analysis of part (422 nt) of the gene for the RNA polymerase ss subunit (rpoB) from various strains indicated that sexual isolation of ATCC 17641 increased with nucleotide sequence divergence. Implications of the observed great heterogeneity in transformability, competence levels and sexual isolation among strains are discussed with regard to the evolution of P. stutzeri.
Idiosyncratic control of the center of mass in expert climbers

Here, we studied posture and movement coordination adopted by expert climbers. The investigation of such expertise might be of particular interest to gain understanding about the mechanisms underlying the biomechanical control of vertical quadrupedal locomotion. A novel custom setup was developed to analyze the motion of the center‐of‐mass (COM) and complementary information about the dynamic distribution of vertical reaction forces under the feet during climbing in nine elite climbers (EC) and nine control subjects. Two adaptive features were found in EC. First, unexpectedly they tended to maintain larger COM distances from the wall relative to controls, during both the static and dynamic phases of vertical motion (by ∼5 cm in both cases). Second, while the control subjects tended to restrain the lateral motion of the COM, all EC demonstrated systematic COM oscillations (∼1.3 times larger) associated with a significant alternating dynamic redistribution of the body weight between the limbs during the double support phase. The latter phenomenon likely reflects an adopted basic climbing strategy in experts. Furthermore, a convergence of the optimal solution towards a more diagonal climbing strategy in EC may shed light on the origin of the diagonal gait in primates and early hominids habituated to quadrupedal vertical locomotion.
Phosphatidylglycerol Is Essential for Oligomerization of Photosystem I Reaction Center1

Our earlier studies with the pgsA mutant of Synechocystis PCC6803 demonstrated the important role of phosphatidylglycerol (PG) in PSII dimer formation and in electron transport between the primary and secondary electron-accepting plastoquinones of PSII. Using a long-term depletion of PG from pgsA mutant cells, we could induce a decrease not only in PSII but also in PSI activity. Simultaneously with the decrease in PSI activity, dramatic structural changes of the PSI complex were detected. A 21-d PG depletion resulted in the degradation of PSI trimers and concomitant accumulation of monomer PSI. The analyses of PSI particles isolated by MonoQ chromatography showed that, following the 21-d depletion, PSI trimers were no longer detectable in the thylakoid membranes. Immunoblot analyses revealed that the PSI monomers accumulating in the PG-depleted mutant cells do not contain PsaL, the protein subunit thought to be responsible for the trimer formation. Nevertheless, the trimeric structure of PSI reaction center could be restored by readdition of PG, even in the presence of the protein synthesis inhibitor lincomycin, indicating that free PsaL was present in thylakoid membranes following the 21-d PG depletion. Our data suggest an indispensable role for PG in the PsaL-mediated assembly of the PSI reaction center.
Development and Actual Use of 275KV Low-Loss Self-Contained Oil-Filled Cables with Laminated Paper Insulated

This paper summarizes the development of two kinds of new 275kV self-contained oil-filled cables which are insulated with Polypropylene Laminated Paper (PPLP) or Fluorinated Ethylene Propylene Copolymer Laminated Paper (FEP/C) and kraft paper, respectively. Prototype cables were manufactured, tested in the factories, and subjected to an accelerated longterm (1-1/2 year) field test. After the successful field test, these two kinds of cables have been utilized in a main commercial transmission line of the Kansai Electric Power Co., Inc. since November 1982.
The Synthetic N-Terminal Peptide of Human Lactoferrin, hLF(1-11), Is Highly Effective against Experimental Infection Caused by Multidrug-Resistant Acinetobacter baumannii

ABSTRACT The lactoferrin-derived peptide hLF(1-11), but not its control peptide, was highly effective against five multidrug-resistant Acinetobacter baumannii strains in vitro (3 to 4 log reduction) and against four of these strains in an experimental infection in mice (2 to 3 log reduction). Therefore, this peptide is a promising candidate as a novel agent against infections with multidrug-resistant A. baumannii.
Efficient Responses in a Murine Renal Tumor Model by Electroloading Dendritic Cells With Whole-Tumor Lysate

Electroporation of dendritic cells (DCs) with tumor lysate elicited greater antitumor responses in vitro and in vivo, using less lysate than standard coincubation. Electroloaded DCs had normal surface marker expression and matured into competent antigen-presenting cells. In a renal carcinoma (RENCA) model, mice were pretreated with lysate-loaded DCs before tumor challenge. Mice that received DCs electroloaded with RENCA lysate had significantly smaller tumors (9 ± 6 mm2) than mice given DCs coincubated with the same lysate (23 ± 5 mm2). To evaluate a metastatic therapeutic tumor model, mice were first injected with Lewis lung carcinoma (LLC) and then given 2 doses of cryopreserved LLC lysate-loaded DCs. Mice treated with electroloaded DCs had a 50% reduction in lung metastases compared with control mice that received no DCs or DCs loaded with liver lysate. In contrast, DCs coincubated with LLC lysate were indistinguishable from controls. Tumor lysate-electroloaded but not-coincubated DCs also primed syngeneic mouse splenocytes in vitro to produce interferon-γ and, specifically, lyse tumor cells. The electroloaded DCs elicited specific T-cell responses with less lysate than the amount reported in standard coincubation procedures. This approach may be particularly useful when small amounts of tumor material are available.
Two measurement techniques for assessing subtalar joint position: a reliability study.

Proper assessment of the subtalar joint is critical for foot and ankle evaluation. Yet, reliability of open kinetic chain goniometric measurements of the subtalar joint has been poor. Two alternative techniques, navicular height and calcaneal position with an inclinometer, have been reported in the literature but lack reliability assessment. The purpose of this study was to determine the intertester and intratester reliability of navicular height and calcaneal position using an inclinometer. Thirty healthy, volunteer subjects (22 females, age 24 +/- 3.6 years; eight males, age 25 +/- 5.1 years) participated in this study. Two testers performed repeated measures on both feet of each subject (N = 60) during two testing sessions. Testers determined the 1) subtalar neutral position, 2) resting position, and 3) difference between these two measurements using an inclinometer for calcaneal position and navicular height. Intratester and intertester reliabilities (ICC 2, 1), standard errors of measurement, and 95% confidence intervals were determined. Intertester and intratester reliability for calcaneal position ranged from . 68 to . 91 for all measurements. Intertester and intratester reliability for navicular height ranged from . 73 to . 96 for all measurements. We conclude that these weight-bearing measurement techniques are reliable and acceptable for clinical and research purposes as measured. In addition, we hypothesize that these measurement techniques are simpler than previously described open kinetic chain methods.
Ileal Cytokine Dysregulation in Experimental Necrotizing Enterocolitis Is Reduced by Epidermal Growth Factor

BackgroundNecrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We have shown in previous studies that proinflammatory interleukin-18 and interleukin-12 are up-regulated in the ileum of rats with experimental NEC and that epidermal growth factor (EGF) reduces the development of disease. Here we investigated whether the protective effects of EGF are a result of changes in ileal interleukin-18, interleukin-12 and/or antiinflammatory interleukin-10. MethodsNewborn rats were artificially fed with either growth-factor–free rat milk substitute (RMS) or RMS supplemented with 500 ng/mL EGF (RMS + EGF) and NEC was induced via exposure to asphyxia and cold stress. Cytokine expression and localization were assessed using reverse-transcription real-time polymerase chain reaction and immunohistology/confocal microscopy. ResultsEnteral administration of EGF (RMS + EGF) decreased overproduction of interleukin-18 and increased interleukin-10 production in the ileum. Furthermore, increased interleukin-10 production was associated with up-regulation of the transcription factor Sp1 in RMS + EGF rats. ConclusionsThese data suggest that EGF may reduce NEC via increased interleukin-10 and decreased interleukin-18 and that EGF-mediated up-regulation of Sp1 may account for the increased interleukin-10.
Ca2+‐dependent generation of mitochondrial reactive oxygen species serves as a signal for poly(ADP‐ribose) polymerase‐1 activation during glutamate excitotoxicity

Mitochondrial Ca2+ uptake and poly(ADP‐ribose) polymerase‐1 (PARP‐1) activation are both required for glutamate‐induced excitotoxic neuronal death. Since activation of the glutamate receptors can induce increased levels of reactive oxygen species (ROS), we investigated the relationship of mitochondrial Ca2+ uptake and ROS generation, and the possibility that ROS increase is a required signal for PARP‐1 activation in cultured striatal neurons. Based on the spatial profile of NMDA‐induced ROS generation, we found that only mitochondria showed a significant ROS increase within 30 min after NMDA receptor activation. This ROS increase was inhibited by the mitochondrial complex inhibitors rotenone and oligomycin, but not by the cytosolic phospholipase A2 or xanthine oxidase inhibitors. Mitochondrial ROS generation was also inhibited by both removal of Ca2+ from extracellular medium and blockage of mitochondrial Ca2+ uptake by either a mitochondrial uncoupler or a Ca2+ uniporter inhibitor. Furthermore, both DNA damage and PARP‐1 activation induced by NMDA treatment was inhibited by blocking mitochondrial Ca2+ uptake or by antioxidants. Our results demonstrate that ROS production during the early stage of acute excitotoxicity derives primarily from mitochondria and is Ca2+‐dependent. More importantly, the increase of mitochondrial ROS serves as a signal for PARP‐1 activation, suggesting that concomitant mitochondrial Ca2+ uptake and PARP‐1 activation constitute a unified mechanism for excitotoxic neuronal death.
A common mutation in the lipoprotein lipase gene promoter, -93T/G, is associated with lower plasma triglyceride levels and increased promoter activity in vitro.

Single-strand conformational polymorphism analysis of the lipoprotein lipase promoter identified a T-->G transition at position -93. The frequency in healthy white men was 3.4% (n = 1575). There was an 83% allelic association between -93T-->G and Asp9-->Asn (D9N); all N9 mutations occurred on a -93G allele, but not all -93G mutations occurred on an N9 allele. It was thus possible to assess the effect on plasma triglyceride (Tg) levels of the rare -93G mutation in the presence of the wild-type D9. Carriers of the -93G, with genotype TG/DD, had significantly lower Tg levels than TT/DD individuals (1.36 versus 1.78 mmol/L, P = .01); carriers of both mutations (TG/DN) had the highest Tg levels (1.93 mmol/L). When the group was stratified above and below the sample mean for body mass index (BMI), carriers of the -93G on a D9 allele (TG/DD) were "protected" against the Tg-raising effect of obesity, as assessed by BMI. In Afro-Caribbeans (n = 91), the carrier frequency of -93G was 18-fold higher (63%), with weaker (17%) allelic association between -93G and N9. In vitro, the -93G promoter had 24% higher activity than the -93T in a rat smooth muscle cell line and 18% higher activity in a human adrenal cell line. A protein identified by band-shift assays bound to the -93G but not to the -93T allele, which may explain the lower Tg levels in -93G carriers.