gebhart/patrepeval huggingface dataset:
Sequence analysis of a human RhoGAP domain-containing gene and characterization of its expression in human multiple tissues (2007)

Rho GTPase activating proteins (GAPs) stimulate the intrinsic GTP hydrolysis activity of Rho family proteins. Here we isolated a rhoGAP domain-containing protein gene with the same reading frame with ARHGAP19 gene, which has an ORF of 1485 bp encoding a putative protein of 494 amino acid residues with a predicted molecular mass of 55.806 kDa. Protein pattern analysis shows that it contains a bipartite nuclear localization signal (NLS) besides the rhoGAP domain, and it is consistent with the result of sub-cellular localization. ARHGAP19 is located in chromosome 10q24.1 and consists of 12 exons according to the Blastn result. Weak expression was detected in adult pancreas, spleen, thymus and ovary of the 16 adult tissues examined, while it had a more abundant expression pattern in eight important human fetal tissues. The expression pattern of ARHGAP19 shows it may have functions related to fetus development and gives us some clues on its probable functions in adult tissues.
Evaluation of segmentation methods on head and neck CT: Auto‐segmentation challenge 2015 (2017)

The Head and Neck Auto-Segmentation Challenge 2015 was a good opportunity to assess the current state-of-the-art in segmentation of organs at risk for radiotherapy treatment. Participating teams had the possibility to compare their approaches to other methods under unbiased and standardized circumstances. The results demonstrate a clear tendency toward more general purpose and fewer structure-specific segmentation algorithms.
Mutants of Escherichia coli K12 with Defects in Anaerobic Pyruvate Metabolism (1981)

A strain of Escherichia coli with a mutation in the ana gene was shown to lack acetaldehyde dehydrogenase and alcohol dehydrogenase. The requirement of this strain for an external oxidant to grow anaerobically on glucose shows that the reduction of acetyl-CoA is the principal means of reoxidation of NADH produced during glycolysis in E. coli. Further mutants derived from the ana strain were shown to be affected in the enzymes involved in the fermentation of pyruvate (pyruvate formate-lyase, phosphotransacetylase, acetate kinase). A gene controlling acetate kinase (ackB) activity has been located at 39 min on the chromosomal map. Evidence is presented that anaerobic nitrite reduction with pyruvate involves at least the dehydrogenase subunit of the pyruvate dehydrogenase complex.
Homologous desensitization of the human guanylate cyclase C receptor (2000)

Guanylate Cyclase C (GCC) serves as a receptor for the endogenous ligands, guanylin and uroguanylin, as well as the family of bacterial heat-stable enterotoxins (ST), which are one of the major causes of diarrhoea the world over. We had earlier provided evidence that GCC, present in the human colonic T84 cell line, is desensitized on prolonged exposure to ST, and this desensitization was reflected in a reduced ST-stimulated guanylate cyclase activity of GCC [Bakre, M.M. & Visweswariah, S.S. (1997) FEBS Lett. 408, 345-349]. In this study, we have investigated the mechanisms that underlie this cellular desensitization process. Desensitization of T84 cells was not a result of reduction in GCC present in membranes prepared from desensitized T84 cells, nor due to increased cGMP-phosphodiesterase activity associated with the membrane fraction. The decrease in ST-stimulatable guanylate cyclase activity of GCC was due to a dramatic reduction in the Vmax of the cyclase, which was also seen when MnGTP was used as the substrate. GCC undergoes ligand-induced inactivation in vitro, which is alleviated in the presence of ATP. In vivo desensitized GCC could be further inactivated in vitro when preincubated with ST, indicating that the two mechanisms of GCC inactivation are distinct. Cellular refractoriness as reflected by a reduced responsiveness to further ST-stimulation following prior exposure to IST, coupled with GCC desensitization was also observed in another colonic cell line, Caco2. However, HEK293 cells, stably transfected with GCC cDNA, when exposed to ST for prolonged periods, did not result in GCC desensitization, indicating that desensitization of GCC appeared to be a cell specific phenomenon. GCC expressed in HEK293-GCC cells, however, showed in vitro ligand induced inactivation, suggesting that there are two independent means of ligand-induced desensitization of GCC, perhaps distinct from the mechanisms that have been described earlier for other members of the guanylate cyclase receptor family.
DNA vaccines (2000)

The premise that DNA coding for antigens produces proteins to stimulate the immune system when inoculated directly into muscle tissues, has the immense attractions of simplicity, versatility and economy. When other vaccination approaches are experiencing practical problems, meeting such challenges as AIDS and malaria, considerable attention has focused on DNA vaccines with entire conferences and a flood of commercial companies devoted to exploring the possibilities. A number of clinical trials for both infectious diseases and cancer have already commenced, even though a number of major issues have to be resolved.
Beyond NOTES: randomized controlled study of different methods of flexible endoscopic hemostasis of artificially induced hemorrhage, via NOTES access to the peritoneal cavity (2009)

Regarding the three methods tested, the new prototype FAPC device allowed hemostasis of notable bleeding from a major vessel even more quickly than forceps coagulation of a bleeding side branch. More studies are needed to further explore this potentially very valuable tool.
Polypeptide growth factors and phorbol ester induce progressive ankylosis (Ank) gene expression in murine and human fibroblasts* (2001)

Polypeptide growth factors promote cellular proliferation by binding to specific plasma membrane-anchored receptors. This interaction triggers the phosphorylation of signal transducing molecules and the transcriptional activation of numerous genes. We have used a differential display approach to identify fibroblast growth factor (FGF)-1-inducible genes in murine NIH 3T3 fibroblasts. Here we report that one of these genes encodes ank, a type IIIa transmembrane protein reported to function in cells as an inorganic pyrophosphate transporter. FGF-1 induction of ank mRNA expression is first detectable at 2 h after growth factor addition and is dependent on de novo RNA and protein synthesis. Ank gene expression is also upregulated after treating quiescent fibroblasts with several other mitogenic agents (e.g., calf serum or platelet-derived growth factor-BB) or the tumor promoter phorbol 12-myristate 13-acetate. Furthermore, in comparison to parental NIH 3T3 cells, oncogene-transformed NIH 3T3 cells constitutively express elevated levels of ank mRNA. FGF-1 also increases ank gene expression in non-immortalized human embryonic lung fibroblasts. Finally, the murine and human ank genes are expressed in vivo in a tissue-specific manner, with highest levels of mRNA expression found in brain, heart, and skeletal muscle. These results indicate that ank is a growth factor-regulated delayed-early response gene in mammalian cells, and we propose that increased ank expression during cell cycle progression may be necessary to maintain proper intracellular pyrophosphate levels during conditions of high cellular metabolic activity.
Application of ≊100 Å linewidth structures fabricated by shadowing techniques (1981)

A variety of shadowing techniques have been developed for fabricating simple structures with lines and spaces in the 100 Å linewidth regime. In the basic technique, a smooth vertical step with precisely determined depth is produced in a substrate by reactive ion etching. This step is shadowed at a shallow angle by evaporation in order to deposit material on the vertical wall. The substrate is then etched at normal incidence with an ion beam to remove the thin layer of material outside the step. This leaves a thin rectangular line of material at the step. By alternately evaporating different materials and by adding lithography and etching steps, more complex structures can be made. Applications of these structures in wire grating optical polarizers and the use of long thin wires for studying electron localization are described. Optical polarizers with extinction ratios of nearly 200 to 1 have been made. This demonstrates some of the unique capabilities of the shadowing technique since high quality polarizers require large areas of high aspect ratio ≊100 Å linewidth metal lines.
A Sox1 to Pax6 Switch Drives Neuroectoderm to Radial Glia Progression During Differentiation of Mouse Embryonic Stem Cells (2008)

The transcription factors Sox1 and Pax6 are expressed sequentially during early mouse embryonic neurogenesis. Sox1 expression starts upon formation of neuroectoderm, whereas Pax6 is subsequently expressed in radial glial cells, the latter giving rise to most neurons of the cerebral cortex. Here we used mouse embryonic stem (ES) cells to study the role of Sox1 and Pax6 in regulating differentiation of neural progenitors. For this purpose, we investigated the effect of overexpression and knockdown of Sox1 and Pax6, using three differentiation protocols. We show that (a) expression of Sox1 or Pax6 in uncommitted ES cells favored neuroectodermal lineage choice; (b) continuous Sox1 expression maintained cells at the neuroepithelial stage and prevented expression of Pax6 and other radial glial cell markers; (c) Sox1 knockdown facilitated exit from the progenitor stage, whereas Pax6 knockdown decreased formation of radial glia; (d) forced Pax6 expression in neuroepithelial cells triggered their differentiation into radial glia and neurons; and (e) Pax6 expression induced cell migration, a feature typical of radial glia-derived early neurons. We conclude that Sox1 enhances neuroectodermal commitment and maintenance but blocks further differentiation. In contrast, Pax6 is involved in the progression of neuroectoderm toward radial glia.
Expression of DEP-1, a receptor-like protein-tyrosine-phosphatase, is enhanced with increasing cell density. (1994)

cDNA encoding a receptor-like protein-tyrosine-phosphatase (PTP) termed DEP-1 was isolated from a HeLa cell library. The cDNA predicts an enzyme consisting of an extracellular segment containing eight fibronectin type III repeats, a single transmembrane segment, and a single intracellular PTP domain. Following expression of DEP-1 cDNA in COS cells a glycoprotein of 180 kDa was detected and PTP activity was demonstrated in immunocomplexes with a C-terminal peptide antiserum. Endogenous DEP-1 was detected in WI-38 human embryonic lung fibroblasts by immunoblotting and immunocomplex PTP assays. Immunoblot analysis of DEP-1 expression in WI-38 cells revealed dramatically increased levels and activity of the PTP in dense cultures relative to sparse cultures. Also, DEP-1 activity, detected in PTP assays of immunocomplexes, was increased in dense cell cultures. In contrast, the expression levels of PTP-1B did not change with cell density. This enhancement of DEP-1 expression with increasing cell density was also observed in another fibroblast cell line, AG1518. The increase in DEP-1 occurs gradually with increasing cell contact and is initiated before saturation cell density is reached. These observations suggest that DEP-1 may contribute to the mechanism of contact inhibition of cell growth.
The signal sequence of the p62 protein of Semliki Forest virus is involved in initiation but not in completing chain translocation. (1990)

So far it has been demonstrated that the signal sequence of proteins which are made at the ER functions both at the level of protein targeting to the ER and in initiation of chain translocation across the ER membrane. However, its possible role in completing the process of chain transfer (see Singer, S. J., P. A. Maher, and M. P. Yaffe. Proc. Natl. Acad. Sci. USA. 1987. 84:1015-1019) has remained elusive. In this work we show that the p62 protein of Semliki Forest virus contains an uncleaved signal sequence at its NH2-terminus and that this becomes glycosylated early during synthesis and translocation of the p62 polypeptide. As the glycosylation of the signal sequence most likely occurs after its release from the ER membrane our results suggest that this region has no role in completing the transfer process.
On-line routing of virtual circuits with applications to load balancing and machine scheduling (1997)

In this paper we study the problem of on-line allocation of routes to virtual circuits (both point-to-point and multicast ) where the goal is to route all requests while minimizing the required bandwidth. We concentrate on the case of Permanent virtual circuits (i.e., once a circuit is established it exists forever), and describe an algorithm that achieves on O (log n ) competitive ratio with respect to maximum congestin, where n is the number of nodes in the network. Informally, our results show that instead of knowing all of the future requests, it is sufficient to increase the bandwidth of the communication links by an O (log n ) factor. We also show that this result is tight, that is, for any on-line algorithm there exists a scenario in which Ω(log n ) increase in bandwidth is necessary in directed networks. We view virtual circuit routing as a generalization of an on-line load balancing problem, defined as follows: jobs arrive on line and each job must be assigned to one of the machines immediately upon arrival. Assigning a job to a machine increases the machine's load by an amount that depends both on the job and on the machine. The goal is to minimize the maximum load. For the related machines case, we describe the first algorithm that achieves constant competitive ratio. for the unrelated case (with n machines), we describe a new method that yields O (log n )-competitive algorithm. This stands in contrast to the natural greed approach, whose competitive ratio is exactly n .
Thyroid Hypocalcemic Principle and Recurrent Laryngeal Nerve Injury as Factors Affecting the Response to Parathyroidectomy in Rats1 (1963)

The extent and time course of the hypocalcemia developing in calcium-depleted young male rats during the first 5 hr after parathyroidectomy were found to differ considerably, depending on which one of 3 methods of parathyroidectomy was used. One hr after the operation the serum calcium of thyroparathyroidectomized rats was higher than that of rats parathyroidectomized alone, whether by excision or hot-wire cautery. By the fifth hr, the serum calcium of rats parathyroidectomized by cautery had fallen much lower, that of rats parathyroidectomized by excision had changed very little, and that of thyroparathyroidectomized rats had decreased, but only to the level of the rats parathyroidectomized by excision. It was found that cutting, stretching or burning the recurrent laryngeal nerves resulted in respiratory difficulty and retarded the fall in serum calcium after parathyroidectomy—results similar to those produced by thyroparathyroidectomy. It was concluded that trauma to these nerves, which is unavoidable during thyroparathyroidectomy, was responsible for the observed retardation in the development of hypocalcemia. The serum calcium of rats parathyroidectomized by excision was further depressed by cautery of the thyroid gland, the effect being greater after bilateral than after unilateral cautery, and by injection of a small amount of rat thyroid extract. It was concluded that the excessive fall in serum calcium of rats parathyroidectomized by cautery was due to the release of a hypocalcemic substance from the thyroid gland. The substance was tentatively named “thyrocalcitonin,” and its relation to “calcitonin,” proposed as a parathyroid hypocalcemic hormone by Copp et al., is discussed.
Multiplex gene editing by CRISPR–Cpf1 using a single crRNA array (2016)

Targeting of multiple genomic loci with Cas9 is limited by the need for multiple or large expression constructs. Here we show that the ability of Cpf1 to process its own CRISPR RNA (crRNA) can be used to simplify multiplexed genome editing. Using a single customized CRISPR array, we edit up to four genes in mammalian cells and three in the mouse brain, simultaneously.
Efficient infection of a human T-cell line and of human primary peripheral blood leukocytes with a pseudotyped retrovirus vector. (1996)

Peripheral blood lymphocytes (PBLs) are an important target for gene transfer studies aimed at human gene therapy. However, no reproducibly efficient methods are currently available to transfer foreign, potentially therapeutic genes into these cells. While vectors derived from murine retroviruses have been the most widely used system, their low infection efficiency in lymphocytes has required prolonged in vitro culturing and selection after infection to obtain useful numbers of genetically modified cells. We previously reported that retroviral vectors pseudotyped with vesicular stomatitis G glycoprotein (VSV-G) envelope can infect a wide variety of cell types and can be concentrated to titers of greater than 10(9) infectious units/ml. In this present study, we examined the ability of amphotropic and pseudotyped vectors expressing a murine cell surface protein, B7-1, to infect the human T-cell line Jurkat or human blood lymphocytes. Limiting dilution analysis of transduced Jurkat cells demonstrated that the pseudotyped vector is significantly more efficient in infecting T cells than an amphotropic vector used at the same multiplicity of infection (moi). To identify the transduction efficiency on PBLs, we examined the levels of cell surface expression of the B7-1 surface marker 48 to 72 hr after infection. The transduction efficiency of PBLs with the pseudotyped vector increased linearly with increasing moi to a maximum of approximately 16-32% at an moi of 40. This relatively high efficiency of infection of a T-cell line and of blood lymphocytes with VSV-G pseudotyped virus demonstrates that such modified pseudotyped retrovirus vectors may be useful reagents for studies of gene therapy for a variety of genetic or neoplastic disorders.
The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway (2004)

Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous hyperkinetic attacks that are precipitated by alcohol, coffee, stress and fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene causing PNKD in 50 individuals from eight families. The mutations cause changes (Ala to Val) in the N-terminal region of two MR-1 isoforms. The MR-1L isoform is specifically expressed in brain and is localized to the cell membrane while the MR-1S isoform is ubiquitously expressed and shows diffuse cytoplasmic and nuclear localization. Bioinformatic analysis reveals that the MR-1 gene is homologous to the hydroxyacylglutathione hydrolase (HAGH) gene. HAGH functions in a pathway to detoxify methylglyoxal, a compound present in coffee and alcoholic beverages and produced as a by-product of oxidative stress. Our results suggest a mechanism whereby alcohol, coffee and stress may act as precipitants of attacks in PNKD. Stress response pathways will be important areas for elucidation of episodic disease genetics where stress is a common precipitant of many common disorders like epilepsy, migraine and cardiac arrhythmias.
Potential Physiological Frameworks for Mid‐Season Field Phenotyping of Final Plant Nitrogen Uptake, Nitrogen Use Efficiency, and Grain Yield in Maize (2012)

ABSTRACT Improved phenotyping tools for simultaneously characterizing maize ( Zea mays L.) genotypes with superior grain yield (GY) and N use efficiency (NUE) would be beneficial for breeding progress. Possible phenotypic predictors of the crowding intensity and N availability effects on maize plant N uptake, GY, and NUE were evaluated for different genotypes in two environments. Our objectives were to develop phenotyping framework tools to predict plant N uptake, GY, and NUE via (i) identification of important mid‐season morpho‐physiological traits (from a total of 80 parameters), (ii) assessment of correlations between predictive traits (principal component analyses identified 21 traits), and (iii) arrangement of key traits into sequential pathways of mechanistic functions (3 traits). Plant phenotyping measurements taken during vegetative stages were poor predictors of GY and NUE. Plant N status at silk emergence was strongly associated with grain components. At silking, the chlorophyll contents (Soil Plant Analysis Development [SPAD] readings) were highly correlated to leaf N concentration, and the latter with the N nutrition index (NNI). As expected, NNI fairly reflected plant N uptake at silking and correlated well to relative GY. Maize plant biomass and N uptake at maturity were predicted via stem volume estimation at silking. The latter predictive model accurately simulated both GY and NUE in other field experiments. Physiologically based frameworks for mid‐season prediction of maize GY and NUE require further testing but hold promise.
Structural analysis of the interaction of the pyrimidine tract-binding protein with the internal ribosomal entry site of encephalomyocarditis virus and foot-and-mouth disease virus RNAs. (1996)

Initiation of translation of a subset of eukaryotic mRNAs results from internal ribosomal entry. This process is exemplified by encephalomyocarditis virus (EMCV), which contains an internal ribosomal entry site (IRES) within its 5' nontranslated region that is approximately 450-nt long and consists of a series of stem-loops designated H-L. We have previously identified a cellular 58-kDa polypeptide that binds specifically to this IRES and that is implicated in its function as the pyrimidine tract-binding protein PTB. We have now mapped PTB binding sites directly on the IRES elements of EMCV and the related foot-and-mouth disease virus (FMDV) using structure-specific enzymatic probes and base-specific chemical probes. PTB bound to six sites on the EMCV IRES: site 1 (UCUU401) is upstream of domain H, site 2 is the basal helix of domain H (nt 407-410 and 440-443), site 3 (UCUUU423) is the apical loop of domain H, site 4 is the apical helix and adjacent internal bulged loop of domain K, site 5 (CUUUA750) is the apical loop of domain K, and site 6 (CCUUU815) is downstream of domain L. PTB bound to sites on the FMDV IRES that correspond precisely to EMCV sites 3, 5, and 6. These sites have the consensus sequence CUUU and form two groups that are located near to the 5' and 3' borders of these IRES elements. Their position, and the effects of mutation of them on IRES function are consistent with PTB's role in IRES-mediated initiation being to bind to multiple sites in the IRES, thereby stabilizing a specific active conformation.
[Significance of ursodeoxycholic acid in the eradication of Helicobacter pylori]. (1996)

In this pilot study we investigated the value of a fourteen-day regimen with amoxicillin (1 g bid), ranitidine (300 mg/d) and ursodeoxycholic acid (300 mg tid) in eradicating Helicobacter pylori. 15 patients with non-ulcer dyspepsia (reactive CLO test, positive histology or 13C urea breath test) were enrolled. Helicobacter pylori was eradicated in 6 of 13 patients (13C urea breath test 4 weeks after the end of treatment). 2 patients were not followed up because of too short treatment (< 1 week). Only 5/15 patients had no side effects (33%). These results strongly suggest that ursodeoxycholic acid in this application regimen is not of use in eradicating Helicobacter pylori.