gebhart/patrepeval huggingface dataset:
Role of calcium as an inhibitor of rat liver carbamylphosphate synthetase I. (1984)

The mechanism of Ca2+ inhibition of carbamylphosphate synthetase I has been investigated using purified enzyme obtained from livers of rats fed a high protein diet. Binding of Mn2+ to the enzyme was measured by EPR techniques at pH 7.8, and Scatchard plots of the data indicated one Mn2+-binding site with a K'd of 13 microM. From competition studies between Mn2+ and Ca2+ or Mg2+ binding, values of 180 microM were obtained for K'd (Mg) and 193 microM for K'd (Ca). A nonlinear least squares curve fitting program was used to calculate the K'm for MgATP2- at the metal-nucleotide binding sites using a simplified rate equation of the enzyme reaction mechanism. Values of 140 and 2420 microM were obtained for K'm (MgATP) at the first and second sites, respectively, at pH 7.8, with a free Mg2+ of 1 mM and other substrates and activators present at saturating concentrations. Variations of the bicarbonate, N-acetylglutamate, and ammonia concentrations in the absence and presence of different amounts of total calcium, from which free Ca2+, free Mg2+, MgATP2-, and CaATP2- concentrations were calculated, permitted values for K'i (CaATP) to be obtained by graphic procedures. Mean values of 375 and 120 microM were obtained for K'i (CaATP) at the first and second sites, respectively. Using the above kinetic constants, a computer model of the enzyme reaction was constructed and tested using two further sets of kinetic data obtained by varying the concentrations of Mg2+, Ca2+, MgATP2-, and CaATP2-. Poor fits were obtained unless the formation of a mixed complex involving CaATP2- competition with MgATP2- at the second metal-nucleotide-binding site was incorporated into the rate equation. Nonlinear least squares curve fitting of both sets of experimental data gave a well determined value of 124 microM for this final CaATP2- inhibitory constant. Sensitivity tests for variation of the primary kinetic constants with the computer model showed that the inhibitory effect of free Ca2+ was weak and that the observed calcium inhibition of carbamylphosphate synthetase can be accounted for primarily by competitive interaction of CaATP2- at the second MgATP2- binding site. With 1 mM free Mg2+ and 5 mM MgATP2-, half-maximal inhibition of enzyme activity was obtained with 0.2 mM CaATP2-.
Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic approach (2003)

The majority of our patients benefited greatly from laser-derived 308-nm UVB therapy, which cleared skin lesions faster than conventional phototherapy. As this therapy targets only the involved skin, the thickness of the plaques and individual MED-I should determine the initial dose, thus increasing the effectiveness of the therapy. We propose that light therapy sparing uninvolved skin will become predominant in the future.
Measurement of biological activities of purified and crude enterotoxin of Clostridium perfringens (1975)

Enterotoxin of Clostridium perfringens was assayed and compared with toxicity in mice and erythemal activity in guinea pigs. Conversion factors were used to express these biological activities of crude enterotoxin in terms of weight of pure enterotoxin protein. One microgram of enterotoxin was equivalent to 3.41 erythema units and to 0.68 mouse median lethal dose.
Syntheses of 3-hydroxymethyl-2,3-dihydrobenzofurans and 3-hydroxymethylbenzofurans (2003)

Reactions of 2-hydroxyphenylmethanones 8 with 1-chloro-1-(benzotriazol-1-yl)alkanes 9 give intermediates 10a-h , which were converted by trimethylsulfonium iodide to oxirans 11a-h. Treatment of 11a-h with LDA gave either 3-hydroxymethyl-2,3-dihydrobenzofurans or 3hydroxymethylbenzofurans depending on substituents.
Safety and efficacy of 22 weeks of treatment with sapropterin dihydrochloride in patients with phenylketonuria (2008)

Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation, which can lead to neurocognitive and neuromotor impairment. Sapropterin dihydrochloride, an FDA-approved synthetic formulation of tetrahydrobiopterin (6R-BH4, herein referred to as sapropterin) is effective in reducing plasma Phe concentrations in patients with hyperphenylalaninemia due to tetrahydrobiopterin (BH4)-responsive PKU, offering potential for improved metabolic control. Eighty patients, > or =8 years old, who had participated in a 6-week, randomized, placebo-controlled study of sapropterin, were enrolled in this 22-week, multicenter, open-label extension study comprising a 6-week forced dose-titration phase (5, 20, and 10 mg/kg/day of study drug consecutively for 2 weeks each), a 4-week dose-analysis phase (10 mg/kg/day), and a 12-week fixed-dose phase (patients received doses of 5, 10, or 20 mg/kg/day based on their plasma Phe concentrations during the dose titration). Dose-dependent reductions in plasma Phe concentrations were observed in the forced dose-titration phase. Mean (SD) plasma Phe concentration decreased from 844.0 (398.0) micromol/L (week 0) to 645.2 (393.4) micromol/L (week 10); the mean was maintained at this level during the study's final 12 weeks (652.2 [382.5] micromol/L at week 22). Sixty-eight (85%) patients had at least one adverse event (AE). All AEs, except one, were mild or moderate in severity. Neither the severe AE nor any of the three serious AEs was considered related to sapropterin. No AE led to treatment discontinuation. Sapropterin is effective in reducing plasma Phe concentrations in a dose-dependent manner and is well tolerated at doses of 5-20 mg/kg/day over 22 weeks in BH4-responsive patients with PKU.
Both p21ras and pp60v-src are required, but neither alone is sufficient, to activate the Raf-1 kinase. (1992)

The raf genes encode a family of cytoplasmic proteins with intrinsic protein-serine/threonine kinase activity. The c-raf gene is the cellular homolog of v-raf, the transforming gene of murine sarcoma virus 3611. The constitutive kinase activity of the v-Raf protein has been implicated in transformation and mitogenesis. The activity of Raf-1, the protein product of the c-raf gene, is normally suppressed by a regulatory N-terminal domain. Activation of various tyrosine-kinase growth factor receptors results in activation of Raf-1 and its hyperphosphorylation. Further, Raf-1 has been shown to act either downstream or independently of the p21ras protein, as indicated by experiments involving microinjection of anti-Ras antibodies. To investigate the potential role of p21ras in the activation of Raf-1 by tyrosine kinases, we have used the baculovirus/Sf9 cell system to overproduce various wild-type and mutant forms of pp60src, p21ras, and Raf-1 proteins. We show that either pp60v-src or p21c-ras can independently activate the autokinase activity of Raf-1, but only to a limited extent. Surprisingly, both pp60v-src and p21c-ras are required to fully activate Raf-1. Analysis of the Raf-1 autokinase activity in vitro shows that Raf-1 autophosphorylation sites are distributed equally on serine and threonine residues. When Raf-1 is analyzed by immunoblotting, as previously reported for mammalian cell experiments, a marked increase in the apparent molecular weight of Raf-1 is seen only when it is coexpressed with both pp60v-src and p21ras.
High-resolution image recovery from image-plane arrays, using convex projections (1989)

We consider the problem of reconstructing remotely obtained images from image-plane detector arrays. Although the individual detectors may be larger than the blur spot of the imaging optics, high-resolution reconstructions can be obtained by scanning or rotating the image with respect to the detector. As an alternative to matrix inversion or least-squares estimation [Appl. Opt. 26, 3615 (1987)], the method of convex projections is proposed. We show that readily obtained prior knowledge can be used to obtain good-quality imagery with reduced data. The effect of noise on the reconstruction process is considered.
Transfer Mechanisms of Electronic Excitation Energy (1960)

Th. Förster, Transfer Mechanisms of Electronic Excitation Energy, Radiation Research Supplement, Vol. 2, Bioenergetics: Considerations of Processes of Absorption, Stabilization, Transfer, and Utilization. Proceedings of a Symposium Sponsored by the U. S. Atomic Energy Commission Held at Brookhaven National Laboratory, October 12-16, 1959 (1960), pp. 326-339
Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters (2001)

The findings give some useful indications for the electrical parameter setting in deep brain stimulation of the STN, and some information about the mechanism of action of deep brain stimulation.
Thermally Triggered Calcium Phosphate Formation from Calcium-Loaded Liposomes (1998)

A thermally triggered liposome-based mineralization system is described that is metastable at ambient temperature but rapidly forms calcium phosphate mineral upon warming to physiologic temperature. Mixing of a calcium-loaded lipid vesicle suspension with aqueous inorganic phosphate resulted in a stable liposome suspension whose bulk ionic concentration was highly supersaturated with respect to hydroxyapatite and other calcium phosphate minerals. The mineralization activity of metastable liposome suspensions was found to be strongly dependent both on temperature and on the composition of the phospholipids that comprise the vesicle membrane. No detectable mineral formation occurred in the metastable liposome suspensions during storage for several weeks at room temperature. However, when the liposome suspensions were heated to near the lipid chain melting transition (Tm), Ca2+ was released from the lipid vesicles and reacted with extravesicular phosphate to form calcium phosphate mineral. Infrared spectroscopy and powder X-ray diffraction analysis of the reaction products indicated the formation of both apatite and brushite minerals, a finding that is consistent with the changing pH conditions of thermally triggered mineralization. Mixtures of miscible phospholipids (dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine) were used to tailor Tm to physiologic temperature. This strategy was employed for the preparation of metastable liposome suspensions that were stable for long periods of time at room temperature but that mineralized rapidly when heated to 37 °C. The potential medical and dental significance of thermally triggered liposomal mineralization is discussed.
NextflowWorkbench: Reproducible and Reusable Workflows for Beginners and Experts (2016)

ABSTRACT Computational workflows and pipelines are often created to automate series of processing steps. For instance, workflows enable one to standardize analysis for large projects or core facilities, but are also useful for individual biologists who need to perform repetitive data processing. Some workflow systems, designed for beginners, offer a graphical user interface and have been very popular with biologists. In practice, these tools are infrequently used by more experienced bioinformaticians, who may require more flexibility or performance than afforded by the user interfaces, and seem to prefer developing workflows with scripting or command line tools. Here, we present a workflow system, the NextflowWorkbench (NW), which was designed for both beginners and experts, and blends the distinction between user interface and scripting language. This system extends and reuses the popular Nextflow workflow description language and shares its advantages. In contrast to Nextflow, NextflowWorkbench offers an integrated development environment that helps complete beginners get started with workflow development. Auto-completion helps beginners who do not know the syntax of the Nextflow language. Reusable processes provide modular workflows. Programmers will benefit from unique interactive features that help users work more productively with docker containers. We illustrate this tool with a workflow to estimate RNA-Seq counts using Kallisto. We found that beginners can be taught how to assemble this workflow in a two hours training session. NW workflows are portable and can execute on laptop/desktop computers with docker, on a lab cluster, or in the cloud to facilitate training. NextflowWorkbench is open-source and available at http://workflow.campagnelab.org .
Autotrophic CO 2 fixation via the reductive tricarboxylic acid cycle in different lineages within the phylum Aquificae : evidence for two ways of citrate cleavage (2006)

Autotrophic carbon fixation was characterized in representative members of the three lineages of the bacterial phylum Aquificae. Enzyme activity measurements and the detection of key genes demonstrated that Aquificae use the reductive tricarboxylic acid (TCA) cycle for autotrophic CO(2) fixation. This is the first time that strains of the Hydrogenothermaceae and 'Desulfurobacteriaceae' have been investigated for enzymes of autotrophic carbon fixation. Unexpectedly, two different mechanisms of citrate cleavage could be identified within the Aquificae. Aquificaceae use citryl-CoA synthetase and citryl-CoA lyase, whereas Hydrogenothermaceae and 'Desulfurobacteriaceae' use ATP citrate lyase. The first mechanism is likely to represent the ancestral version of the reductive TCA cycle. Sequence analyses further suggest that ATP citrate lyase formed by a gene fusion of citryl-CoA synthetase and citryl-CoA lyase and subsequently became involved in a modified version of this pathway. However, rather than having evolved within the Aquificae, our phylogenetic analyses indicate that Aquificae obtained their ATP citrate lyase through lateral gene transfer. Aquificae play an important role in biogeochemical processes in a variety of high-temperature habitats. Thus, these findings substantiate the hypothesis that autotrophic carbon fixation through the reductive TCA cycle is widespread and contributes significantly to biomass production particularly in hydrothermal habitats.
Neglected evidence in idiopathic pulmonary fibrosis and the importance of early diagnosis and treatment (2014)

In idiopathic pulmonary fibrosis (IPF), some facts or concepts based on substantial evidence, whilst implicit for learned subspecialists, have previously been neglected and/or not explicitly formulated or made accessible to a wider audience. IPF is strongly associated with cigarette smoking and is predominantly a disease of ageing. However, its cause(s) remain elusive and, thus, it is one of the most challenging diseases for the development of novel effective and safe therapies. With the approval of pirfenidone for patients with mild-to-moderate IPF, an earlier diagnosis of IPF is a prerequisite for earlier treatment and, potentially, improvement of the long-term clinical outcome of this progressive and ultimately fatal disease. An earlier diagnosis may be achieved in IPF by promoting thin-slice chest high-resolution computed tomography screening of interstitial lung disease as a "by-product" of large-scale lung cancer screening strategies in smokers, but other techniques, which have been neglected in the past, are now available. Lung auscultation and early identification of "velcro" crackles has been proposed as a key component of early diagnosis of IPF. An ongoing study is exploring correlations between lung sounds on auscultation obtained using electronic stethoscopes and high-resolution computed tomography patterns.
MUSCLE: multiple sequence alignment with high accuracy and high throughput (2004)

We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the log-expectation score, and refinement using tree-dependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.
Enhanced coexpression of thioredoxin and high mobility group protein 1 genes in human hepatocellular carcinoma and the possible association with decreased sensitivity to cisplatin. (1996)

Thioredoxin (TRX), a disulfide-reducing intracellular protein, functions as a cellular defense mechanism against oxidative stress. In this study, we asked whether expression of TRX, glutathione-thiol transferase pi, and high mobility group protein 1 (HMG-1) genes is enhanced in human hepatocellular carcinoma and whether expression of these genes is associated with sensitivity to cisplatin. Both TRX and HMG-1 were co-overexpressed in almost all cancerous lesions in comparison to normal tissue in surgically resected hepatocellular carcinomas of 20 patients. Tumor sensitivity to cisplatin [cis-diamminedichloroplatinum (II)], but not to mitomycin C or doxorubicin, correlated with mRNA levels of TRX in cancer tissue. TRX and HMG-1 may be useful tumor markers, and TRX might be also a useful marker for sensitivity to cisplatin in human hepatocellular carcinomas.
A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding. (1993)

Synaptotagmin I is a Ca(2+)- and phospholipid-binding protein of synaptic vesicles with an essential function in neurotransmission. Ca2+/phospholipid binding by synaptotagmin I may be mediated by its C2 domains, sequence motifs that have been implicated in the Ca2+ regulation of a variety of proteins. However, it is currently unknown if C2 domains are sufficient for Ca2+/phospholipid binding or if they even directly participate in Ca2+/phospholipid binding. In order to address this question, we have studied the Ca2+/phospholipid-binding properties of the first C2 domain of synaptotagmin I. Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity. The C2 domain is specific for negatively charged phospholipids and for those divalent cations that are known to stimulate synaptic vesicle exocytosis (Ca2+ > Sr2+, Ba2+ >>> Mg2+). These studies establish that C2 domains can serve as independently folding Ca2+/phospholipid-binding domains. Furthermore, the cation specificity and the cooperativity of Ca2+ binding by the C2 domain from synaptotagmin I support a role for this protein in mediating the Ca2+ signal in neurotransmitter release.
Inflorescence Commitment and Architecture in Arabidopsis (1997)

Flowering plants exhibit one of two types of inflorescence architecture: indeterminate, in which the inflorescence grows indefinitely, or determinate, in which a terminal flower is produced. The indeterminate condition is thought to have evolved from the determinate many times, independently. In two mutants in distantly related species, terminal flower 1 in Arabidopsis and centroradialis in Antirrhinum, inflorescences that are normally indeterminate are converted to a determinate architecture. The Antirrhinum gene CENTRORADIALIS (CEN) and the Arabidopsis gene TERMINAL FLOWER 1 (TFL1) were shown to be homologous, which suggests that a common mechanism underlies indeterminacy in these plants. However, unlike CEN, TFL1 is also expressed during the vegetative phase, where it delays the commitment to inflorescence development and thus affects the timing of the formation of the inflorescence meristem as well as its identity.
Sensitivity and reproducibility of standardized-competitive RT-PCR for transcript quantification and its comparison with real time RT-PCR (2004)

Probe based detection assays form the mainstay of transcript quantification. Problems with these assays include varying hybridization efficiencies of the probes used for transcript quantification and the expense involved. We examined the ability of a standardized competitive RT-PCR (StaRT PCR) assay to quantify transcripts of 4 cell cycle associated genes (RB, E2F1, CDKN2A and PCNA) in two cell lines (T24 & LD419) and compared its efficacy with the established Taqman real time quantitative RT-PCR assay. We also assessed the sensitivity, reproducibility and consistency of StaRT PCR. StaRT PCR assay is based on the incorporation of competitive templates (CT) in precisely standardized quantities along with the native template (NT) in a PCR reaction. This enables transcript quantification by comparing the NT and CT band intensities at the end of the PCR amplification. The CT serves as an ideal internal control. The transcript numbers are expressed as copies per million transcripts of a control gene such as β-actin (ACTB). The NT and CT were amplified at remarkably similar rates throughout the StaRT PCR amplification cycles, and the coefficient of variation was least (<3.8%) when the NT/CT ratio was kept as close to 1:1 as possible. The variability between the rates of amplification in different tubes subjected to the same StaRT PCR reaction was very low and within the range of experimental noise. Further, StaRT PCR was sensitive enough to detect variations as low as 10% in endogenous actin transcript quantity (p < 0.01 by the paired student's t-test). StaRT PCR correlated well with Taqman real time RT-PCR assay in terms of transcript quantification efficacy (p < 0.01 for all 4 genes by the Spearman Rank correlation method) and the ability to discriminate between cell types and confluence patterns. StaRT PCR is thus a reliable and sensitive technique that can be applied to medium-high throughput quantitative transcript measurement. Further, it correlates well with Taqman real time PCR in terms of quantitative and discriminatory ability. This label-free, inexpensive technique may provide the ability to generate prognostically important molecular signatures unique to individual tumors and may enable identification of novel therapeutic targets.
Semi-supervised multi-label learning by constrained non-negative matrix factorization (2006)

We present a novel framework for multi-label learning that explicitly addresses the challenge arising from the large number of classes and a small size of training data. The key assumption behind this work is that two examples tend to have large overlap in their assigned class memberships if they share high similarity in their input patterns. We capitalize this assumption by first computing two sets of similarities, one based on the input patterns of examples, and the other based on the class memberships of the examples. We then search for the optimal assignment of class memberships to the unlabeled data that minimizes the difference between these two sets of similarities. The optimization problem is formulated as a constrained Non-negative Matrix Factorization (NMF) problem, and an algorithm is presented to efficiently find the solution. Compared to the existing approaches for multi-label learning, the proposed approach is advantageous in that it is able to explore both the unlabeled data and the correlation among different classes simultaneously. Experiments with text categorization show that our approach performs significantly better than several state-of-the-art classification techniques when the number of classes is large and the size of training data is small.