gebhart/patrepeval huggingface dataset:
Membrane-bound hydrogenase and sulfur reductase of the hyperthermophilic and acidophilic archaeon Acidianus ambivalens (2003)

A sulfur reductase (SR) and a hydrogenase were purified from solubilized membrane fractions of anaerobically grown cells of the sulfur-dependent archaeon Acidianus ambivalens and the corresponding genes were sequenced. The SR reduced elemental sulfur with hydrogen as electron donor [45 U (mg protein)(-1)] in the presence of hydrogenase and either 2,3-dimethylnaphthoquinone (DMN) or cytochrome c in the enzyme assay. The SR could not be separated from the hydrogenase during purification without loss of activity, whereas the hydrogenase could be separated from the SR. The specific activity of the hydrogenase was 170 U (mg protein)(-1) with methyl viologen and 833 U (mg protein)(-1) with DMN as electron acceptors. Both holoenzymes showed molecular masses of 250 kDa. In SDS gels of active fractions, protein bands with apparent masses of 110 (SreA), 66 (HynL), 41 (HynS) and 29 kDa were present. Enriched hydrogenase fractions contained 14 micro mol Fe and 2 micromol Ni (g protein)(-1); in addition, 2.5 micromol Mo (g protein)(-1) was found in the membrane fraction. Two overlapping genomic cosmid clones were sequenced, encoding a five-gene SR cluster (sre) including the 110 kDa subunit gene (sreA), and a 12-gene hydrogenase cluster (hyn) including the large and small subunit genes and genes encoding proteins required for the maturation of NiFe hydrogenases. A phylogenetic analysis of the SR amino acid sequence revealed that the protein belonged to the DMSO reductase family of molybdoenzymes and that the family showed a novel clustering. A model of sulfur respiration in Acidianus developed from the biochemical results and the data of the amino acid sequence comparisons is discussed.
Antiadhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro (2004)

Multicellular resistance, a subtype of therapeutic resistance manifested in cancer cells grown as three-dimensional multicellular masses, such as spheroids in vitro and solid tumors in vivo, occurs with respect to a variety of anticancer treatment strategies including chemotherapy, ionizing radiation, and even host-mediated antibody-dependent cellular cytotoxicity. Previous studies from our laboratory have shown that multicellular resistance to chemotherapy demonstrated by aggregates of EMT-6 murine mammary carcinoma cells can be overcome by using hyaluronidase to disrupt intercellular adhesive interactions and associated patterns of protein expression. In this proof of principle study, we explored the concept of antiadhesive chemosensitization in the context of human cancer cells by using a monoclonal antibody to disrupt E-cadherin-mediated cell-cell interactions in multicellular spheroids of HT29 human colorectal adenocarcinoma. In so doing, we found that disruption of E-cadherin-mediated adhesion sensitizes multicellular spheroids of HT29 in vitro to treatment with 5-fluorouracil, paclitaxel, vinblastine, and etoposide but not cisplatin. Furthermore, we have found that antibody-mediated blockage of E-cadherin function leads to decreased expression and activity of protein kinase C alpha and beta1, both of which have previously been implicated in chemoresistance exhibited by HT29 cells; however, we have found that the chemosensitization effects of the anti-E-cadherin antibody are independent of its influence on protein kinase C beta1.
Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor. (1991)

The high-affinity receptor for human granulocyte/macrophage colony-stimulating factor (hGM-CSF) is composed of two subunits, alpha and beta. The alpha subunit binds GM-CSF with low affinity, whereas the beta subunit does not bind GM-CSF by itself. The alpha and beta subunits together form the high-affinity GM-CSF receptor. The beta subunit has extensive sequence homology with the mouse interleukin 3 (IL-3) receptor (AIC2A) and its homologue (AIC2B) that does not bind IL-3 or other cytokines including GM-CSF. To examine the function of these receptor components, we expressed the alpha subunit of the hGM-CSF receptor with the human beta subunit or the mouse AIC2A or AIC2B in a mouse IL-3-dependent pro-B-cell line, Ba/F3, and in a mouse IL-2-dependent T-cell line, CTLL2. Coexpression of the alpha and beta subunits in Ba/F3 and CTLL2 cells resulted in high-affinity hGM-CSF binding and growth response to low concentrations of hGM-CSF. Whereas Ba/F3 cells expressing the alpha subunit alone proliferated in response to high concentrations of hGM-CSF, CTLL2 cells expressing the alpha subunit alone did not respond to hGM-CSF at all. Since Ba/F3 cells express endogenous AIC2A and AIC2B whereas CTLL2 expresses neither of them, we examined the possibility that either AIC2A or AIC2B is involved in the formation of a functional GM-CSF receptor. The expression of the human alpha subunit with AIC2B, but not with AIC2A, in CTLL2 cells conferred a growth response to hGM-CSF. These results indicate that the beta subunit of the GM-CSF receptor is required for generation of growth signals and that AIC2B is likely the beta subunit of the mouse GM-CSF receptor.
Carbohydrate-Based Synthetic Approach to Control Toxicity Profiles of Folate−Drug Conjugates (2010)

To better regulate the biodistribution of the vinblastine-folate conjugate, EC145, a new folate-spacer that incorporates 1-amino-1-deoxy-D-glucitol-gamma-glutamate subunits into a peptidic backbone, was synthesized. Synthesis of Fmoc-3,4;5,6-di-O-isopropylidene-1-amino-1-deoxy-D-glucitol-gamma-glutamate 20, suitable for Fmoc-strategy solid-phase peptide synthesis (SPPS), was achieved in four steps from delta-gluconolactone. Addition of alternating glutamic acid and 20 moieties onto a cysteine-loaded resin, followed by the addition of folate, deprotection, and cleavage, resulted in the isolation of the new folate-spacer: Pte-gammaGlu-(Glu(1-amino-1-deoxy-D-glucitol)-Glu)(2)-Glu(1-amino-1-deoxy-D-glucitol)-Cys-OH (21). The addition of 21 to an appropriately modified desacetylvinblastine hydrazide (DAVLBH) resulted in a conjugate (25) with an improved therapeutic index. Treatment of 25 with DTT in neutral buffer at room temperature demonstrated that free DAVLBH would be released under the reductive environment of the internalized endosome.
The scanning model for translation: an update. (1989)

The small (40S) subunit of eukaryotic ribosomes is believed to bind initially at the capped 5'-end of messenger RNA and then migrate, stopping at the first AUG codon in a favorable context for initiating translation. The first-AUG rule is not absolute, but there are rules for breaking the rule. Some anomalous observations that seemed to contradict the scanning mechanism now appear to be artifacts. A few genuine anomalies remain unexplained.
Advances in click chemistry for silica-based material construction (2016)

Click chemistry is undoubtedly the most powerful 1,3-dipolar cycloaddition reaction in organic synthesis.
Quantum mechanical modeling of the charge distribution Si/Si/sub 1-x/Ge/sub x/Si p-channel MOSFET (2002)

Incorporation of a Si/sub 1-x/Ge/sub x/ alloy layer in the channel of a p-channel MOSFET has been proposed as a means to improve device performance. In order to achieve optimal performance in such a device, the inversion charge distribution must be located in the alloy channel layer where the carrier mobility is highest. The smaller bandgap of the Si/sub 1-x/Ge/sub x/ alloy layer, compared to Si, creates a potential well in which the carriers can reside. Understanding how the carriers distribute themselves under various gate bias conditions is necessary in order to achieve optimal device design. The authors' aim is to demonstrate the dependence of the charge distribution in a Si/Si/sub 1-x/Ge/Si p-channel MOSFET based on the self-consistent solution of the Schrodinger-Poisson equations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analysis of transmit-receive diversity in rayleigh fading (2003)

We analyze the error performance of a wireless communication system employing transmit-receive diversity in Rayleigh fading. By focusing on the complex Gaussian statistics of the independent and identically distributed entries of the channel matrix, we derive a formula for the characteristic function (c.f.) of the maximum output signal-to-noise ratio. We use this c.f. to obtain a closed-form expression of the symbol error probability (SEP) for coherent binary keying. The method is easily extended to obtain the SEP for the coherent reception of M-ary modulation schemes.
Identification of an immunodominant neutralizing and protective epitope from measles virus fusion protein by using human sera from acute infection (1997)

Polyclonal sera obtained from African children with acute measles were used to screen a panel of 15-mer overlapping peptides representing the sequence of measles virus (MV) fusion (F) protein. An immunodominant antigenic region from the F protein (p32; amino acids 388 to 402) was found to represent an amino acid sequence within the highly conserved cysteine-rich domain of the F protein of paramyxoviruses. Epitope mapping of this peptide indicated that the complete 15-amino-acid sequence was necessary for high-affinity interaction with anti-MV antibodies. Immunization of two strains of mice with the p32 peptide indicated that it was immunogenic and could induce antipeptide antibodies which cross-reacted with and neutralized MV infectivity in vitro. Moreover, passive transfer of antipeptide antibodies conferred significant protection against fatal rodent-adapted MV-induced encephalitis in susceptible mice. These results indicate that this epitope represents a candidate for inclusion in a future peptide vaccine for measles.
Automatic multiscale enhancement and segmentation of pulmonary vessels in CT pulmonary angiography images for CAD applications (2007)

The authors are developing a computerized pulmonary vessel segmentation method for a computer-aided pulmonary embolism (PE) detection system on computed tomographic pulmonary angiography (CTPA) images. Because PE only occurs inside pulmonary arteries, an automatic and accurate segmentation of the pulmonary vessels in 3D CTPA images is an essential step for the PE CAD system. To segment the pulmonary vessels within the lung, the lung regions are first extracted using expectation-maximization (EM) analysis and morphological operations. The authors developed a 3D multiscale filtering technique to enhance the pulmonary vascular structures based on the analysis of eigenvalues of the Hessian matrix at multiple scales. A new response function of the filter was designed to enhance all vascular structures including the vessel bifurcations and suppress nonvessel structures such as the lymphoid tissues surrounding the vessels. An EM estimation is then used to segment the vascular structures by extracting the high response voxels at each scale. The vessel tree is finally reconstructed by integrating the segmented vessels at all scales based on a "connected component" analysis. Two CTPA cases containing PEs were used to evaluate the performance of the system. One of these two cases also contained pleural effusion disease. Two experienced thoracic radiologists provided the gold standard of pulmonary vessels including both arteries and veins by manually tracking the arterial tree and marking the center of the vessels using a computer graphical user interface. The accuracy of vessel tree segmentation was evaluated by the percentage of the "gold standard" vessel center points overlapping with the segmented vessels. The results show that 96.2% (2398/2494) and 96.3% (1910/1984) of the manually marked center points in the arteries overlapped with segmented vessels for the case without and with other lung diseases. For the manually marked center points in all vessels including arteries and veins, the segmentation accuracy are 97.0% (4546/4689) and 93.8% (4439/4732) for the cases without and with other lung diseases, respectively. Because of the lack of ground truth for the vessels, in addition to quantitative evaluation of the vessel segmentation performance, visual inspection was conducted to evaluate the segmentation. The results demonstrate that vessel segmentation using our method can extract the pulmonary vessels accurately and is not degraded by PE occlusion to the vessels in these test cases.
Vaginal Fluid and Serum CEA, CA125 and SCC in Normal Conditions and in Benign and Malignant Diseases of the Genital Tract (1997)

Carcinoembryonic antigen (CEA), CA125, and squamous cell carcinoma antigen (SCC) were evaluated in paired vaginal fluid and serum samples from 69 women, mean age 40.6 (20-78) years. Fifteen of the subjects were normal females (controls), 12 were pregnant, 20 had benign gynecological diseases, 5 presented severe cervical dysplasias and 17 suffered from cancer of the genital tract. Highly elevated CEA, CA125 and SCC concentrations (median, range) were found in vaginal fluid: 186 ng/ml (12-5420); 890 U/ml (54-65000); 1600 ng/ml (27-13000) respectively, compared with those in the paired serum samples: 1 ng/ml (0.5-8.6); 12 U/ml (3.0-1590); 1 ng/ml (0.3-19). Vaginal fluid CEA, CA125 and SCC values were significantly different among the five studied groups (p < 0.0002; p < 0.02: p < 0.002 respectively), being significantly higher in the patients with benign gynecological diseases, compared with those in the patients with malignancies of the genital tract (p < 0.0001; p < 0.02; p < 0.005), and those in controls (p < 0.02; p < 0.007; p < 0.02 respectively). The results of this study suggest that: 1) CEA, CA125 and SCC seem to be normal constituents of vaginal fluid. 2) The distribution of CEA, CA125 and SCC between vaginal fluid and the circulation is affected by pregnancy, inflammation and cancer of the genital tract.
Function and Evolutionary Origin of Unicellular Camera-Type Eye Structure (2015)

The ocelloid is an extraordinary eyespot organelle found only in the dinoflagellate family Warnowiaceae. It contains retina- and lens-like structures called the retinal body and the hyalosome. The ocelloid has been an evolutionary enigma because of its remarkable resemblance to the multicellular camera-type eye. To determine if the ocelloid is functionally photoreceptive, we investigated the warnowiid dinoflagellate Erythropsidinium. Here, we show that the morphology of the retinal body changed depending on different illumination conditions and the hyalosome manifests the refractile nature. Identifying a rhodopsin gene fragment in Erythropsidinium ESTs that is expressed in the retinal body by in situ hybridization, we also show that ocelloids are actually light sensitive photoreceptors. The rhodopsin gene identified is most closely related to bacterial rhodopsins. Taken together, we suggest that the ocelloid is an intracellular camera-type eye, which might be originated from endosymbiotic origin.
Anti-tumor effects of the bacterium caulobacter crescentus in murine tumor models (2006)

Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.
Inferring Orthology and Paralogy (2012)

The distinction between orthologs and paralogs, genes that started diverging by speciation versus duplication, is relevant in a wide range of contexts, most notably phylogenetic tree inference and protein function annotation. In this chapter, we provide an overview of the methods used to infer orthology and paralogy. We survey both graph-based approaches (and their various grouping strategies) and tree-based approaches, which solve the more general problem of gene/species tree reconciliation. We discuss conceptual differences among the various orthology inference methods and databases, and examine the difficult issue of verifying and benchmarking orthology predictions. Finally, we review typical applications of orthologous genes, groups, and reconciled trees and conclude with thoughts on future methodological developments.
Thin-Film, Ultra High-Density Microelectrocorticographic Decoding of Speech Sounds in Human Superior Temporal Gyrus (2016)

Abstract not provided
Effect of denosumab on prolonging bone-metastasis-free survival (BMFS) in men with nonmetastatic castrate-resistant prostate cancer (CRPC) presenting with aggressive PSA kinetics. (2012)

6 Background: Denosumab, an anti-RANK-ligand monoclonal antibody, has been shown to prolong BMFS by a median 4.2 months and with a 15% risk reduction vs. placebo in men with non-metastatic CRPC and baseline PSA value ≥ 8.0 ng/mL and/or PSA doubling time (DT) ≤ 10.0 months. To determine the efficacy of denosumab in men at greatest risk for bone metastases, we evaluated BMFS in a subset of men with PSADT &lt; 6 months, a cutoff based on a previous report (Smith MR, et al: J Clin Oncol. 23:2918-2925, 2005). Methods: 1432 men with non-metastatic CRPC (baseline [median] PSA: 12.3 ng/mL, PSADT: 5.1 months, ADT duration: 47.1 months) were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or placebo. The first patient enrolled February 2006; primary analysis cut-off was July 2010, when &gt; 660 men had developed bone metastasis or died. The primary endpoint was BMFS (time to first bone metastasis or death from any cause). BMFS results are presented for men with baseline PSADT &lt; 6 months. Results: Median BMFS in the placebo group of men with PSADT &lt; 6 months was 6.5 months shorter than for the placebo group in the full population (18.7 months vs. 25.2 months), indicating that these men are at particularly high risk. In this group of men with PSADT &lt; 6 months, denosumab prolonged BMFS by a median of 7.2 months and with a 23% reduction in risk compared with placebo (Table). Conclusions: Patients with shortened PSADT are at higher risk of developing bone metastasis and denosumab is markedly effective at prolonging BMFS in this subset of patients. [Table: see text]
Investigations on Reaction Mechanisms in a Surface Modification Resist Process Using Chemical Vapor Deposition of Polysiloxane (1997)

A surface modification resist process (SMR), in which polysiloxane is formed on the exposed resist surface by chemical vapor deposition, was studied for subquarter micron pattern fabrication. This paper describes the microscopic and macroscopic reaction mechanisms in SMR when methyltriethoxysilane is used as the chemical vapor deposition gas. Hydrolysis and condensation reactions occurring in acid‐catalyzed polysiloxane formation were investigated through Fourier transform infrared spectroscopy. It was demonstrated that the hydrolysis is the dominant reaction rather than the condensation, and is dependent on the generated acid catalyst and sorbed water. Polysiloxane layer growth at the near resist surface was observed by Rutherford backscattering spectroscopy and from cross‐sectional views of the polysiloxane layer. The polysiloxane layer initially grows in the resist film because of the dominant diffusion of methyltriethoxysilane molecules. Afterward the diffusion is prevented due to the excessive networking of the polysiloxane so that the polysiloxane layer grows on the resist surface. Furthermore, 0.20 μm pattern fabrication was demonstrated by applying SMR to KrF excimer laser lithography with an alternating phase‐shifting mask.
Use of A-192621 and IRL-2500 to Unmask the Mesenteric and Renal Vasodilator Role of Endothelin ETB Receptors (2002)

Endothelin-1 (ET-1) is known to cause a transient (<1 min) depressor followed by a sustained (>1 h) pressor response. The former through the activation of ET(B) receptors, and the latter through the activation of ET(A) and ET(B) receptors. This study examines if ET(B) receptors mediate sustained mesenteric and renal dilation in anesthetized rats. Intravenous bolus ET-1 (0.8, 1.4, and 2 nmol/kg) and IRL-1620 (ET(B) agonist, 2, 5, and 10 nmol/kg) caused transient decrease followed by sustained increases in mean arterial pressure (MAP) that were accompanied by increases in total peripheral resistance (TPR), reductions in cardiac output (CO), and mesenteric and renal vasoconstriction. Pretreatment with FR-139317 (ET(A) antagonist, 1 mg/kg) attenuated the pressor and constrictor effects of ET-1 but did not alter responses to IRL-1620. IRL-2500 (ET(B) antagonist, 5 mg/kg) slightly inhibited the renal constrictor effect of IRL-1620, whereas A-192621 (ET(B) antagonist, 5 mg/kg) abolished all hemodynamic responses to IRL-1620. Both IRL-2500 and A-192621 markedly enhanced MAP, TPR, and mesenteric, and the renal constrictor effects of ET-1. Therefore, A-192621 was more effective than IRL-2500 in blocking IRL-1620-induced vasoconstriction, but both augmented constrictor responses to ET-1. The potentiation of ET-1-induced vasoconstriction by ET(B) receptor antagonists revealed a sustained vasodilator role of ET(B) receptors.
Granulocyte colony stimulating factor treatment for neonatal neutropenia. (1995)

In a pilot study recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered to 12 neutropenic preterm infants to determine if neonatal neutropenia is secondary to decreased endogenous G-CSF production. Respiratory variables were monitored because of the possible link between inflammatory cells and hyaline membrane disease. All infants showed increased neutrophil counts. The only possible side effect observed was an exacerbation of thrombocytopenia.
CRISP-ID: decoding CRISPR mediated indels by Sanger sequencing (2016)

The advent of next generation gene editing technologies has revolutionized the fields of genome engineering in allowing the generation of gene knockout models and functional gene analysis. However, the screening of resultant clones remains challenging due to the simultaneous presence of different indels. Here, we present CRISP-ID, a web application which uses a unique algorithm for genotyping up to three alleles from a single Sanger sequencing trace, providing a robust and readily accessible platform to directly identify indels and significantly speed up the characterization of clones.