gebhart/patrepeval huggingface dataset:
Processing of Japanese encephalitis virus non-structural proteins: NS2B-NS3 complex and heterologous proteases (1995)

Processing of Japanese encephalitis (JE) virus non-structural (NS) proteins expressed by recombinant vaccinia viruses was analysed to characterize the responsible viral protease. Analysis of the processing of polyprotein NS2A-2B-3' containing the N-terminal 322 amino acids of NS3 revealed products consistent with cleavages at the predicted intergenic junctions as well as at one or possibly two sites within NS2A. Cleavage at the alternate site(s) containing the cleavage sequence motif within NS2A could possibly explain the production of the NS1' protein in JE virus-infected cells. Polyprotein NS2A-d2B-3' containing a large deletion within NS2B was cleavage-defective, despite the presence of the proposed NS3 protease domain. Cleavage of NS2A-d2B-3' was restored if NS2B or NS2A-2B was supplied in trans, providing evidence that NS2B is strictly required for NS3 proteolytic activity. NS2B- or NS3-specific sera raised against the bacterial TrpE fusion protein co-precipitated NS2B and NS3 or NS3' from the lysate of JE virus or recombinant virus-infected cells. Thus both protease components are associated as a complex, presumably representing the active JE virus protease. JE virus and the analogous dengue 4 (DEN-4) protease components were employed to examine the activity of heterologous proteases. The defective cleavage of JE virus NS2A-d2B-3' was complemented by heterologous DEN-4 NS2B, whereas the defective cleavage of DEN-4 NS2A-d2B-3' was not corrected by heterologous JE virus NS2B. This suggests that the heterologous JE virus NS2B-DEN-4 NS3 protease is not active, despite the considerable sequence conservation of NS2B and NS3 between the two viruses. The cleavage activity was restored by replacement of the C-terminal 80 amino acids of JE virus NS2B with the corresponding DEN-4 sequence, consistent with the notion that the C-terminal region contains amino acid residues for interaction with DEN-4 NS3.
Biochemical characterization of a Naegleria TET-like oxygenase and its application in single molecule sequencing of 5-methylcytosine (2015)

Modified DNA bases in mammalian genomes, such as 5-methylcytosine ((5m)C) and its oxidized forms, are implicated in important epigenetic regulation processes. In human or mouse, successive enzymatic conversion of (5m)C to its oxidized forms is carried out by the ten-eleven translocation (TET) proteins. Previously we reported the structure of a TET-like (5m)C oxygenase (NgTET1) from Naegleria gruberi, a single-celled protist evolutionarily distant from vertebrates. Here we show that NgTET1 is a 5-methylpyrimidine oxygenase, with activity on both (5m)C (major activity) and thymidine (T) (minor activity) in all DNA forms tested, and provide unprecedented evidence for the formation of 5-formyluridine ((5f)U) and 5-carboxyuridine ((5ca)U) in vitro. Mutagenesis studies reveal a delicate balance between choice of (5m)C or T as the preferred substrate. Furthermore, our results suggest substrate preference by NgTET1 to (5m)CpG and TpG dinucleotide sites in DNA. Intriguingly, NgTET1 displays higher T-oxidation activity in vitro than mammalian TET1, supporting a closer evolutionary relationship between NgTET1 and the base J-binding proteins from trypanosomes. Finally, we demonstrate that NgTET1 can be readily used as a tool in (5m)C sequencing technologies such as single molecule, real-time sequencing to map (5m)C in bacterial genomes at base resolution.
High-level production of biologically active human alpha 1-antitrypsin in Escherichia coli. (1984)

A cDNA clone containing the complete human alpha 1-antitrypsin sequence was isolated from a human liver cDNA bank by screening with a chemically synthesized oligonucleotide probe. DNA sequences encoding the alpha 1-antitrypsin mature polypeptide were inserted into an Escherichia coli expression vector that allows transcription from the efficient leftward promoter of bacteriophage lambda (PL) and initiation of translation at the lambda cII gene ribosome-binding site. This construction resulted in the induction of a 45-kilodalton protein at a level of approximately 15% of total cell protein. The polypeptide produced was recognized by antisera raised against human alpha 1-antitrypsin protein and displayed normal biological activity in an in vitro antielastase assay.
Edge-Guided Single Depth Image Super Resolution (2015)

Recently, consumer depth cameras have gained significant popularity due to their affordable cost. However, the limited resolution and the quality of the depth map generated by these cameras are still problematic for several applications. In this paper, a novel framework for the single depth image superresolution is proposed. In our framework, the upscaling of a single depth image is guided by a high-resolution edge map, which is constructed from the edges of the low-resolution depth image through a Markov random field optimization in a patch synthesis based manner. We also explore the self-similarity of patches during the edge construction stage, when limited training data are available. With the guidance of the high-resolution edge map, we propose upsampling the high-resolution depth image through a modified joint bilateral filter. The edge-based guidance not only helps avoiding artifacts introduced by direct texture prediction, but also reduces jagged artifacts and preserves the sharp edges. Experimental results demonstrate the effectiveness of our method both qualitatively and quantitatively compared with the state-of-the-art methods.
Transcription from two promoters and autoregulation contribute to the control of expression of the Salmonella typhimurium flagellar regulatory gene flgM (1993)

The flgM gene product has been shown to be a negative regulator of flagellin transcription in Salmonella typhimurium (K. L. Gillen and K. T. Hughes, J. Bacteriol. 173:2301-2310, 6453-6459, 1991; K. Ohnishi, K. Kutsukake, H. Suzuki, and T. Iino, Mol. Microbiol. 6:3149-3157, 1992). Mud-lac fusions to the flgM gene were isolated and used to characterize the regulation of flgM gene expression. Transcription of the flgM gene was decreased more than 30-fold in strains with the flagellar master regulatory genes, flhC and flhD, deleted. A class 2 flagellar defect caused a slight increase of flgM gene transcription unless a wild-type copy of the flgM gene was present, in which case transcription was decreased threefold. A deletion in the gene for the alternative sigma factor sigma 28 (FliA) caused a fourfold decrease in flgM expression. Insertional inactivation of a gene upstream of the flgM gene (flgA) in a fliA mutant strain caused transcription of the flgM gene to be decreased to a basal level. Northern (RNA) blot analysis confirmed the presence of two transcripts through the flgM gene, one which initiates upstream of the flgM gene and a second which initiates upstream of the flgA gene.
WNT antagonist, SFRP1, is Hedgehog signaling target (2006)

Hedgehog and WNT signaling pathways network together during embryogenesis and carcinogenesis. Hedgehog signaling in intestinal epithelium represses canonical WNT signaling to restrict expression of WNT target genes to stem or progenitor cells; however, the mechanism remains unclear. The Hedgehog signal is transduced to GLI family transcription factors though Patched receptor, Smoothened signal transducer, and other signaling components, such as KIF27, KIF7, STK36, SUFU, and DZIP1. Here, we searched for the GLI-binding site within the promoter region of genes encoding secreted-type WNT signal inhibitors, including SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, DKK1, DKK2, DKK3, DKK4, and WIF1. The GLI-binding site was identified within the human SFRP1 promoter based on bioinformatics and human intelligence. The chimpanzee SFRP1 gene was identified within the NW_110515.1 genome sequence. The GLI-binding site of the human SFRP1 promoter was conserved in chimpanzee SFRP1, mouse Sfrp1, and rat Sfrp1 promoters. SFRP1 is the evolutionarily conserved target of the Hedgehog-GLI signaling pathway. Expression domain analyses based on text mining revealed that Indian Hedgehog (IHH), SFRP1, and WNT6 are expressed in differentiated intestinal epithelial cells, mesenchymal cells, and stem/progenitor cells, respectively. Hedgehog is secreted from differentiated epithelial cells to induce SFRP1 expression in mesenchymal cells, which keeps differentiated epithelial cells away from the effects of canonical WNT signaling. These facts indicate that SFRP1 is the Hedgehog target to confine canonical WNT signaling within stem or progenitor cells. Therefore, epigenetic CpG hypermethylation of the SFRP1 promoter during chronic persistent inflammation and aging leads to the occurrence of gastrointestinal cancers, such as colorectal cancer and gastric cancer, through the breakdown of Hedgehog-dependent WNT signal inhibition.
First Zoea of a Rare Deep-sea Shrimp Vexillipar repandum Chace, 1988 (Crustacea, Decapoda, Caridea, Alpheidae), with Special Reference to Larval Characters of the Family (1998)

First zoea of a rare alpheid shrimp Vexillipar repandum Chace, associated with a deep-sea hexactinellid sponge, is described and illustrated based on laboratory-hatched material. The general morphology of the first zoea of V. repandum is similar to those of the previously-known examples of Alpheus. A diagrammatic key for identification of the family among caridean zoeas is proposed.
Activation of the transcription factor NFAT1: concerted or modular regulation? (2004)

The transcription factor NFAT1 is activated through dephosphorylation of multiple serine residues, contained within the SRR1 and SP motifs. The phosphorylation status of these motifs regulates the subcellular localisation of NFAT1 via a conformational switch. Here, we discuss two molecular mechanisms for NFAT1 activation that resemble network-oriented approaches. In the modular mechanism, import and export are regulated separately by the SRR1 and SP motifs, respectively, whereas in the concerted model all residues jointly control both processes. Using simulations of a computational model, we show that both mechanisms may be compatible with recent experimental data on the import and export kinetics of NFAT1.
A first look at the Oxford Nanopore MinION sequencer (2014)

Oxford Nanopore's third-generation single-molecule sequencing platform promises to decrease costs for reagents and instrumentation. After a 2-year hiatus following the initial announcement, the first devices have been released as part of an early access program. We explore the performance of this platform by resequencing the lambda phage genome, and amplicons from a snake venom gland transcriptome. Although the handheld MinION sequencer can generate more than 150 megabases of raw data in one run, at most a quarter of the resulting reads map to the reference, with less than average 10% identity. Much of the sequence consists of insertion/deletion errors, or is seemingly without similarity to the template. Using the lambda phage data as an example, although the reads are long, averaging 5 kb, at best 890 ± 1932 bases per mapped read could be matched to the reference without soft clipping. In the course of a 36 h run on the MinION, it was possible to resequence the 48 kb lambda phage reference at 16× coverage. Currently, substantially larger projects would not be feasible using the MinION. Without increases in accuracy, which would be required for applications such as genome scaffolding and phasing, the current utility of the MinION appears limited. Library preparation requires access to a molecular laboratory, and is of similar complexity and cost to that of other next-generation sequencing platforms. The MinION is an exciting step in a new direction for single-molecule sequencing, though it will require dramatic decreases in error rates before it lives up to its promise.
Clamping down on weak terminal base pairs: oligonucleotides with molecular caps as fidelity-enhancing elements at the 5'- and 3'-terminal residues (2004)

The base-pairing fidelity of oligonucleotides depends on the identity of the nucleobases involved and the position of matched or mismatched base pairs in the duplex. Nucleobases forming weak base pairs, as well as a terminal position favor mispairing. We have searched for 5'-appended acylamido caps that enhance the stability and base-pairing fidelity of oligonucleotides with a 5'-terminal 2'-deoxyadenosine residue using combinatorial synthesis and MALDI-monitored nuclease selections. This provided the residue of 4-(pyren-1-yl)butyric acid as a lead. Lead optimization gave (S)-N-(pyren-1-ylmethyl)pyrrolidine-3-phosphate as a cap that increases duplex stability and base-pairing fidelity. For the duplex of 5'-AGGTTGAC-3' with its fully complementary target, this cap gives an increase in the UV melting point T(m) of +10.9 degrees C. The T(m) is 6.3-8.3 degrees C lower when a mismatched nucleobase faces the 5'-terminal dA residue. The optimized cap can be introduced via automated DNA synthesis. It was combined with an anthraquinone carboxylic acid residue as a cap for the 3'-terminal residue. A doubly capped dodecamer thus prepared gives a melting point decrease for double-terminal mismatches that is 5.7-5.9 degrees C greater than that for the unmodified control duplex.
Characterization of Gene Expression in Resting and Activated Mast Cells (1998)

To characterize gene expression in activated mast cells more comprehensively than heretofore, we surveyed the changes in genetic transcripts by the method of serial analysis of gene expression in the RBL-2H3 line of rat mast cells before and after they were stimulated through their receptors with high affinity for immunoglobulin E (FcepsilonRI). A total of 40,759 transcripts derived from 11,300 genes were analyzed. Among the diverse genes that had not been previously associated with mast cells and that were constitutively expressed were those for the cytokine macrophage migration inhibitory factor neurohormone receptors such as growth hormone- releasing factor and melatonin and components of the exocytotic machinery. In addition, several dozen transcripts were differentially expressed in response to antigen-induced clustering of the FcepsilonRI. Included among these were the genes for preprorelaxin, mitogen-activated protein kinase kinase 3, and the dual specificity protein phosphatase, rVH6. Significantly, the majority of genes differentially expressed in this well-studied model of mast cell activation have not been identified before this analysis.
A phase I and pharmacologic evaluation of the DNA intercalator CI-958 in patients with advanced solid tumors. (2000)

5-[(2-Aminoethyl)amino]-2-[2-(diethylamino)ethyl]-2H-[1]benzothiopyra no[4,3,2-cd]-indazol-8-ol trihydrochloride (CI-958) is the most active member of a new class of DNA intercalating compounds, the benzothiopyranoindazoles. Because of its broad spectrum and high degree of activity as well as a favorable toxicity profile in preclinical models, CI-958 was chosen for further development. The Phase I study described here was undertaken to determine the toxicity profile, maximum tolerated dose, and pharmacokinetics of CI-958 given as an i.v. infusion every 21 days. Adult patients with advanced refractory solid tumors who had adequate renal, hepatic, and hematological function, life expectancy, and performance status were eligible for this study. Written informed consent was obtained from all patients. Patients received a 1- or 2-h infusion of CI-958 at 21-day intervals. The starting dose was 5.2 mg/m2, and at least three patients were evaluated at each dose level before proceeding to a new dose level. A pharmacokinetically guided dose escalation design was used until reaching a predetermined target area under the plasma concentration versus time curve (AUC), after which a modified Fibonacci scheme was used. Forty-four patients (21 men and 23 women; median age, 59 years) received 162 courses of CI-958. Neutropenia and hepatorenal toxicity were the dose-limiting toxicities, which defined the maximum tolerated dose of CI-958 to be 875 mg/m2 when given as a 2-h infusion every 21 days. There were no tumor responses. Two patients had stable disease for >250 days. The recommended Phase II dose is 560 mg/m2 for patients with significant prior chemotherapy and 700 mg/m2 for patients with minimal prior chemotherapy. Pharmacokinetic analysis of plasma and urine concentration-time data from each patient was performed. At the recommended Phase II dose of 700 mg/m2, mean CI-958 clearance was 370 ml/min/m2, mean AUC was 33800 ng-h/ml, and mean terminal half-life (t1/2) was 15.5 days. The clearance was similar at all doses, and plasma CI-958 AUC increased proportionally with dose, consistent with linear pharmacokinetics. The percentage reduction in absolute neutrophil count from baseline was well predicted by AUC using a simple Emax model. The pharmacokinetically guided dose escalation saved five to six dose levels in reaching the maximum tolerated dose compared with a standard dose escalation scheme. This may represent the most successful application to date of this dose escalation technique.
Determination of streptomycin sulphate with the method of ponceau S spectrophotometric (2010)

In the condition of pH 4.0～5.0,ponceau S reacted with streptomycin sulphate to form ion-association 1∶1 complex,which faded the color of ponceau S and generated a new absorption.The maximum fading wavelength was at 537 nm and the absorption wavelength was at 575 nm.The content of streptomycin sulphate was determinated with the difference between the best faded peak valve and the new absorption peak value.The apparent molar absorptivity(e) was 1.25×104 L·mol-1·cm-1 and Beer's law is obeyed under the concentration range 1.46～58.30 mg·L-1,a detection limit was 0.91 mg·L-1.The relative standard deviation was 1.20%～1.82% for six parallel determinations.The recovery range was 95.6%～102%.The method has been applied for determination of the real sample with a satisfactory result.
The Li Insertion/Extraction Characteristics of Amorphous Silicon Thin Films (2007)

Amorphous hydrogenated silicon (a-Si:H) is known to be a perspective material for negative electrodes of modem lithium-ion batteries. The electrochemical lithium insertion into thin-film a-Si:H electrodes is studied using chronopotentiometry, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The electrodes were grown on stainless-steel substrates by glow discharge at the temperature of T = 100 and 250 °C. The insertion capacity of the films deposited at 250 °C is higher than that of the equally thick films deposited at 100 °C. The increase in the film thickness involves the drastic decrease of the insertion capacity during the potential cycling. An equivalent circuit is suggested for the lithium insertion to the electrodes, which comprises electrolyte resistance and three RC-chains in series, each chain being a parallel connection of a resistance and a constant-phase element, which relate to charge transfer at the silicon/electrolyte interface, charge transport in the passive film on silicon, and the lithium diffusion into the silicon bulk. With the potential cycling in progress, the most significant changes are observed in the chain relating to the passive film. The Li diffusion coefficient in a-Si:H is estimated from data of CV and EIS. It equals D = 4 10 -13 and 10 -13 cm 2 s -1 for electrodes synthesized at a temperature of 100 and 250 °C, respectively.
Synthese von kristallin‐flüssigen Verbindungen. I. n‐Alkyl‐ und n‐Alkoxyderivate des 3‐Hydroxy‐2,5‐diphenyl‐pyrazins (1966)

Abstract Es werden die Synthesen von 2 homologen Reihen des 3‐Hydroxy‐2,5‐diphenyl‐pyrazins und 2‐Benzoyl‐4(5)‐phenyl‐imidazols beschrieben. p‐n‐Alkyl‐ und p‐n‐Alkoxyphenylglyoxal‐hydrate kondensieren unter ammoniakalischen Bedingungen bevorzugt zu den entsprechenden Imidazolylketonen und nur in geringen Ausbeuten zu Hydroxypyrazinen. Die Alkylhomologen des Pyrazins schmelzen ab Äthylderivat zu kristallin‐flüssigen Phasen auf, die dem smektischen Typ angehören. Mit wachsenden Flügelgruppen treten Umwandlungspunkte in diesen Phasen auf. Die beiden ersten Glieder der Ätherreihe haben zusätzlich einen nematischen Bereich. Allen Imidazolylketonen fehlen diese Eigenschaften. Der Einfluß der α‐ständigen Hydroxygruppe am heterocyclischen Mittelstück der gestreckten Molekeln wird diskutiert.
A fluid biopsy as investigating technology for the fluid phase of solid tumors (2012)

Reliable measurement of internal bodily substances and structures is one of the cornerstones of modern medicine. Progress in cancer medicine, like that in many medical fields, must encompass and take advantage of progress in the physical sciences. Historically, the development and refinement of physical sciences-based detection of biological entities precedes periods of great advancements in therapies. To treat broken limbs and arthritis, we are indebted to Conrad Roentgen's discovery of x-rays by which we can evaluate the bones; to apply gamma knife therapy for cancer, we are indebted to Marie Curie's discoveries about radioactivity by which we can eradicate tumors; to manage the complications of diabetes, we are indebted to Tom Clemens, Ames Pharmaceuticals and Dick Bernstein's refinement of direct blood glucose measurement technology by which we can count, hour-to-hour, the waxing and waning of blood sugar levels; to understand anything at all on the cellular level, we are indebted to Antonie van Leeuwenhoek's microscope, by which we can see our cells. The application of physical sciences perspectives to biological and medical problems has a long and productive history. As of late, however, the increasing compartmentalization of science and exponential increases of knowledge in both arenas has resulted in a rift between the two. The NCI has initiated a research network establishing multiple centers of investigation, the Physical Sciences in Oncology Centers (http://physics.cancer.gov), which seek to mend the rift. Each headed by a pair of investigators, one in the physical sciences and one in the biological sciences, the centers seek to bring the advances and breakthroughs of the physical sciences world to bear on the question of cancer.
Signal Transducers and Activators of Transcription: Insights into the Molecular Basis of Oral Cancer (2004)

Recent efforts on developing more direct and effective targets for cancer therapy have revolved around a family of transcription factors known as STATs (signal transducers and activators of transcription). STAT proteins are latent cytoplasmic transcription factors that become activated in response to extracellular signaling proteins. STAT proteins have been convincingly reported to possess oncogenic properties in a plethora of human cancers, including oral and oropharyngeal cancer. Signal transduction pathways mediated by these oncogenic transcription factors and their regulation in oral cancer are the focus of this review.