gebhart/patrepeval huggingface dataset:
Transposon mutagenesis identifies genes which control antimicrobial drug tolerance in stationary-phaseEscherichia coli (2004)

Tolerance to antimicrobial agents is a universal phenomenon in bacteria which are no longer multiplying or whose growth rate slows. Since slowly multiplying bacteria occur in clinical infections, extended periods of antimicrobial chemotherapy are needed to eradicate these organisms and to achieve cure. In this study, the molecular basis of antibiotic tolerance was investigated using transposon mutagenesis. We screened 5000 Escherichia coli Tn10Cam mutants for reduction of kanamycin tolerance in late stationary phase and found that 4935 mutants were able to grow to late stationary phase. Reduced tolerance was observed in nine mutants which became sensitive to killing by kanamycin. The mutant KS639 was the most sensitive one to kanamycin, and its genome was disrupted in an intergenic region which lies between aldB and yiaW open reading frames. This mutant showed increased sensitivity not only to kanamycin but also to gentamicin, ciprofloxacin and rifampicin. Reduced tolerance of KS639 to kanamycin was also observed in a murine thigh infection model. P1 transduction to the wild type strains confirmed that the intergenic region was responsible for the tolerance of the bacterium to antibiotics. Using PCR-directed one-step gene replacement, we inactivated the genes aldB, yiaW and yiaV. We also deleted the intergenic region. There was no difference in kanamycin tolerance between each mutant (DeltaaldB, DeltayiaW and DeltayiaV) and the parental strain. But the mutant lacking the intergenic region showed reduced tolerance to kanamycin. These data suggest that the intergenic region between aldB and yiaW genes may be involved in tolerance to antimicrobial agents in E. coli. Furthermore, they show that it is important in murine infection during antibiotic treatment and lead to a faster kill of the mutant bacteria.
RadioimmunoPET: detection of colorectal carcinoma with positron-emitting copper-64-labeled monoclonal antibody. (1995)

These Phase I/II results suggest that PET with radiolabeled MAbs (radioimmunoPET) may have important applications in clinical oncology, particularly for detecting smaller colorectal tumor foci in the abdomen or pelvis and for determining accurate dosimetry.
T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production. (1995)

The antigen-specific receptors of T and B lymphocytes are generated by somatic recombination between noncontiguous gene segments encoding the variable portions of these molecules. The semirandom nature of this process, while desirable for the generation of diversity, has been thought to exact a high price in terms of sterile (out-of-frame) products. Historically, the majority of T lymphocytes generated in mammals were thought to be useless, either because they generated such sterile rearrangements or because the receptors generated did not appropriately recognize self-molecules (i.e., positive and negative selection). In the studies described here, we characterize the onset of T cell receptor (TCR) alpha and beta chain gene rearrangements and quantitate their progression throughout T cell development. The results show that T cell production efficiency is enhanced through (a) rearrangement of TCR-beta chain genes early during T cell development, with selective expansion of those cells possessing in-frame rearrangements; (b) deletion of sterile rearrangements at the TCR-alpha chain locus through ordered (proximal to distal) sequential recombination; and (c) modification of nonselectable alpha/beta heterodimer specificities through generation and expression of new TCR-alpha chains. In addition, we demonstrate strict correlations between successful TCR-beta gene rearrangement, the onset of TCR-alpha gene rearrangement, rapid cell division, and programmed cell death, which together serve to maintain cell turnover and homeostasis during T cell development.
Spectrally Efficient Quadrature Duobinary Coherent Systems With Symbol-Rate Digital Signal Processing (2011)

An enhanced digital coherent receiver including a novel blind equalization approach and maximum-likelihood sequence detection (MLSD) is proposed for dual-polarization quadrature duobinary (DP-QDB) systems. In virtue of the compact spectrum of DP-QDB signals approaching Nyquist limit, the equalization is implemented at symbol rate, which relaxes the demand on the sampling speed of analog-to-digital converters (ADCs). The proposed symbol-rate receiver is verified by 43 Gb/s experiments in the presence of chromatic dispersion and polarization-mode dispersion. This paper also investigates the tolerances to narrowband optical filtering, ADC sampling phase, duobinary-generating filter bandwidth, laser linewidth, and carrier frequency offset. Detailed modulation format comparisons are made among DP-QDB, DP-quadrature-phase-shift keying (QPSK), DP-8 quadrature amplitude modulation (QAM), and DP-16QAM. It is shown that DP-QDB with MLSD well trades off major requirements on advanced modulation formats.
Triple Decoding of Hepatitis C Virus RNA by Programmed Translational Frameshifting (2003)

Ribosomes can be programmed to shift from one reading frame to another during translation. Hepatitis C virus (HCV) uses such a mechanism to produce F protein from the -2/+1 reading frame. We now report that the HCV frameshift signal can mediate the synthesis of the core protein of the zero frame, the F protein of the -2/+1 frame, and a 1.5-kDa protein of the -1/+2 frame. This triple decoding function does not require sequences flanking the frameshift signal and is apparently independent of membranes and the synthesis of the HCV polyprotein. Two consensus -1 frameshift sequences in the HCV type 1 frameshift signal facilitate ribosomal frameshifts into both overlapping reading frames. A sequence which is located immediately downstream of the frameshift signal and has the potential to form a double stem-loop structure can significantly enhance translational frameshifting in the presence of the peptidyl-transferase inhibitor puromycin. Based on these results, a model is proposed to explain the triple decoding activities of the HCV ribosomal frameshift signal.
Characterisation of renal chloride channel, CLCN5, mutations in hypercalciuric nephrolithiasis (kidney stones) disorders (1997)

Mutations of the renal-specific chloride channel (CLCN5) gene, which is located on chromosome Xp11.22, are associated with hypercalciuric nephrolithiasis (kidney stones) in the Northern European and Japanese populations. CLCN5 encodes a 746 amino acid channel (CLC-5) that has approximately 12 transmembrane domains, and heterologous expression of wild-type CLC-5 in Xenopus oocytes has yielded outwardly rectifying chloride currents that were markedly reduced or abolished by these mutations. In order to assess further the structural and functional relationships of this recently cloned chloride channel, additional CLCN5 mutations have been identified in five unrelated families with this disorder. Three of these mutations were missense (G57V, G512R and E527D), one was a nonsense (R648Stop) and one was an insertion (30:H insertion). In addition, two of the mutations (30:H insertion and E527D) were demonstrated to be de novo, and the G57V and E527D mutations were identified in families of Afro-American and Indian origin, respectively. The G57V and 30:H insertion mutations represent the first CLCN5 mutations to be identified in the N-terminus region, and the R648Stop mutation, which has been observed previously in an unrelated family, suggests that this codon may be particularly prone to mutations. Heterologous expression of the mutations resulted in a marked reduction or abolition of the chloride currents, thereby establishing their functional importance. These results help to elucidate further the structure-function relationships of this renal chloride channel.
Transmission of a procoagulant signal from tissue factor-bearing cells to platelets (1996)

The goal of the current study was to examine the mechanism by which factor VIIa/tissue factor (TF) activity leads to platelet activation as the first step in initiation of coagulation. Adherent, endotoxin-treated monocytes were used as a cellular source of TF. The processes that led to platelet activation were rapid, since incubation of coagulation factors and platelets with TF for as little as 15 s initiated platelet activation. Further, direct contact between the TF source and platelets was not required since incubation of plasma levels of coagulation zymogens and inhibitors with TF generated the initiating signal for platelet activation. We hypothesized that thrombin generation on the cells that contained TF was the initiating signal for platelet activation. To test this hypothesis, factor VIIa, inhibitors, and different combinations of coagulation zymogens were incubated with TF-bearing cells. The supernatants were then transferred to a suspension of unactivated platelets with plasma concentrations of zymogen factors and inhibitors. Platelet activation was much more efficient when all the elements of the IIase complex (factors II, V and X) were preincubated with factor VIIa/TF than when only factor X was incubated with factor VIIa/TF. Finally, TF was incorporated into lipid vesicles containing phosphatidyl choline either with or without phosphatidyl serine. Vesicles without phosphatidyl serine have no IIase activity. Platelets were incubated with TF, coagulation zymogens and inhibitors. Platelet activation only occurred when the lipid vesicles could support IIase activity. We conclude that sufficient thrombin generation occurs on the TF-bearing cell (or TF-bearing vesicle) in the absence of platelets, to provide the procoagulant signal that leads to platelet activation. The activated platelet surface then provides sites for TF-activated factor IXa to recruit factor Xa to bind and assemble into functional Xase and IIase complexes.
Mechanism of Pellet Coat Rupture and Its Effect on Drug Release. (1999)

In the formation of a coated controlled release preparation with functional coat layers, hydroxypropyl-methylcellulose was used to form a diffusion layer which swelled immediately upon wetting. Eudragit RS30D was used to form the outer retention layer. The rupture of pellet coat occurred when the Eudragit RS30D was unable to withstand the expansion in volume due to the influx of water and swelling of the hydroxypropylmethylcellulose diffusion layer. The sucrose core was able to contribute an osmotic effect. The hydrostatic pressure built up within the pellet can cause the pellet coat to rupture. Sodium chloride deposited in the diffusion coat was able to delay the bursting of the pellet coat. This was due to the competition for the imbibed water between sodium chloride and hydroxypropylmethylcellulose. The rupture of the pellet coat did not result in a total failure of the controlled drug delivery mechanism. Similar drug release rates were obtained irrespective whether there was a puncture in the pellet coat or not. Pressure built-up in the region away from the puncture pushed the core material towards the point of puncture and sealed the puncture point. In addition, the swelling of polymer around the point of rupture ensured continuity in the drug diffusion barrier.
COMPARATIVE CHEMICAL COMPOSITION AND ANTIMICROBIAL ACTIVITY FRESH & DRY GINGER OILS (ZINGIBER OFFICINALE ROSCOE) (2010)

The volatile oils from fresh and dried ginger rhizomes ( Nedumangadu variety) (Zingiber officinale Roscoe) were analysed by GC and GC‐MS. Zingiberene was the major compound in both ginger oils. Fresh ginger oil contained geranial (8.5%) as the second main compound and had more oxygenated compounds (29.2%) compared to dry ginger oil (14.4%). The dry ginger oil also contained ar‐curcumene (11%), β‐bisabolene (7.2%), sesquiphellandrene (6.6%) and δ‐cadinene (3.5%). Antimicrobial activity of the oils against Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, Trichoderma spp, Aspergillus niger, Pencillium spp. and Saccharomyces cerevisiae, was assessed by disc diffusion method and results obtained are comparable with the reference compounds. The MIC values of the oils ranged from 10µg/mL to 1 µg/mL which is very significant. The study shows a wide application of ginger oil in the treatment of many bacterial and fungal diseases.
Human Sperm-Zona Pellucida Interaction is Inhibited by an Antiserum against a Hamster Sperm Protein1 (1994)

During epididymal transit, mammalian spermatozoa acquire new surface antigens that may participate in gamete interaction. We have previously described a 26-kDa (P26h) epididymal hamster sperm protein that we propose to be involved in fertilization. In this study, we have searched for an antigenically related protein in the human, and have found that an anti-P26h antiserum recognizes a 34-kDa (P34H) protein on Western blot of human sperm proteins. Immunostaining showed that this protein is localized on the acrosomal cap of human epididymal spermatozoa but not on testicular gametes. The effect of the anti-P26h antiserum on the fertilizing ability of human spermatozoa was evaluated by use of a human zona pellucida binding assay. Compared to the preimmune serum, the antiserum caused a highly significant decrease in the number of sperm bound per zona pellucida. This inhibition was not due to the induction of a premature acrosomal reaction nor to an effect on the motility of the spermatozoa. The antiserum recognizing the P34H human sperm protein had no effect on gamete fusion as determined by the zona-free hamster test. Our results suggest that the human spermatozoon acquires an epididymal protein that shares a common epitope(s) with the P26h hamster sperm protein. The possible involvement of this human sperm antigen in the binding to the zona pellucida is discussed.
Viral Vectors in Cancer Immunotherapy: Which Vector for Which Strategy? (2008)

Gene therapy involves the transfer of genetic information to a target cell to facilitate the production of therapeutic proteins and is now a realistic prospect as a cancer treatment. Gene transfer may be achieved through the use of both viral and non-viral delivery methods and the role of this method in the gene therapy of cancer has been demonstrated. Viruses represent an attractive vehicle for cancer gene therapy due to their high efficiency of gene delivery. Many viruses can mediate long term gene expression, while some are also capable of infecting both dividing and non-dividing cells. Given the broadly differing capabilities of various viral vectors, it is imperative that the functionality of the virus meets the requirements of the specific treatment. A number of immunogene therapy strategies have been undertaken, utilising a range of viral vectors, and studies carried out in animal models and patients have demonstrated the therapeutic potential of viral vectors to carry genes to cancer cells and induce anti-tumour immune responses. This review critically discusses the advances in the viral vector mediated delivery of immunostimulatory molecules directly to tumour cells, the use of viral vectors to modify tumour cells, the creation of whole cell vaccines and the direct delivery of tumour antigens in animal models and clinical trials, specifically in the context of the suitability of vector types for specific strategies.
Shutter‐speed analysis of contrast reagent bolus‐tracking data: Preliminary observations in benign and malignant breast disease (2005)

The standard pharmacokinetic model applied to contrast reagent (CR) bolus-tracking (B-T) MRI (dynamic-contrast-enhanced) data makes the intrinsic assumption that equilibrium transcytolemmal water molecule exchange is effectively infinitely fast. Theory and simulation have suggested that this assumption can lead to significant errors. Recent analyses of animal model experimental data have confirmed two predicted signature inadequacies: a specific temporal mismatch with the B-T time-course and a CR dose-dependent underestimation of model parameters. The most parsimonious adjustment to account for this aspect leads to the "shutter-speed" pharmacokinetic model. Application of the latter to the animal model data mostly eliminates the two signature inadequacies. Here, the standard and shutter-speed models are applied to B-T data obtained from routine human breast examinations. The signature standard model temporal mismatch is found for each of the three invasive ductal carcinoma (IDC) cases and for each of the three fibroadenoma (FA) cases studied. It is effectively eliminated by use of the shutter-speed model. The size of the mismatch is considerably greater for the IDC lesions than for the FA lesions, causing the shutter-speed model to exhibit improved discrimination of malignant IDC tumors from the benign FA lesions compared with the standard model. Furthermore, the shutter-speed model clearly reveals focal "hot spots" of elevated CR perfusion/permeation present in only the malignant tumors.
Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia (2003)

Long term statin treatment significantly lowers Lp(a) in FH patients. However, this reduction was unrelated to changes in intima-media thickness and casts doubt on the importance of Lp(a) in the progression of atherosclerotic disease in these patients.
Tera-scale translation models via pattern matching (2008)

Translation model size is growing at a pace that outstrips improvements in computing power, and this hinders research on many interesting models. We show how an algorithmic scaling technique can be used to easily handle very large models. Using this technique, we explore several large model variants and show an improvement 1.4 BLEU on the NIST 2006 Chinese-English task. This opens the door for work on a variety of models that are much less constrained by computational limitations.
High responsivity GaNAsSb p-i-n photodetectors at 13µm grown by radio-frequency nitrogen plasma-assisted molecular beam epitaxy (2008)

GaNAsSb/GaAs p-i-n photo notdetectors with an intrinsic GaNAsSb photoabsorption layer grown at 350 degrees C, 400 degrees C, 440 degrees C and 480 degrees C, have been prepared using radio-frequency nitrogen plasma-assisted molecular beam epitaxy in conjunction with a valved antimony cracker source. The i-GaNAsSb photoabsorption layer contains 3.3% of nitrogen and 8% of antimony, resulting in DC photo-response up to wavelengths of 1350 nm. The device with i-GaNAsSb layer grown at 350 degrees C exhibits extremely high photoresponsivity of 12A/W at 1.3 microm. These photodetectors show characteristics which strongly suggest the presence of carrier avalanche process at reverse bias less than 5V.
In vitro and in vivo functional characterization of bovine vitamin K-dependent gamma-carboxylase expressed in Chinese hamster ovary cells. (1993)

Coagulation factor IX is a serine protease for which high-level expression of biologically active protein in heterologous cells is limited due to inefficient proteolytic removal of the propeptide as well as vitamin K-dependent carboxylation of multiple amino-terminal glutamic acid residues. We have overexpressed the vitamin K-dependent gamma-carboxylase cDNA and monitored its ability to improve factor IX processing in Chinese hamster ovary (CHO) cells. From amino acid sequence analysis of bovine liver vitamin K-dependent gamma-carboxylase, degenerate oligonucleotides were used to isolate a 3.5-kbp bovine cDNA that encoded a 758-residue open reading frame. Expression of the cDNA in COS-1 and CHO cells yielded 17- and 16-fold increases in the in vitro gamma-carboxylase activity of microsomal preparations, respectively. Anti-serum raised against a predicted peptide sequence reacted with a 94-kDa polypeptide in the partially purified bovine liver preparation as well as in stably transfected CHO cells. The amount of antibody reactivity correlated with the increased ability to carboxylate a peptide substrate in vitro. These results strongly support the conclusion that the cDNA encodes the vitamin K-dependent gamma-carboxylase. Transient transfection of the gamma-carboxylase expression vector into factor IX-expressing CHO cells did not improve the specific procoagulant activity of secreted factor IX. In contrast, transfection of an expression vector encoding the propeptide processing enzyme PACE (paired basic amino acid cleaving enzyme) did improve the specific activity of secreted factor IX by 3-fold. These results demonstrate that the ability of CHO cells to modify glutamic acid residues to gamma-carboxyglutamic acid in secreted factor IX is not limited by the expression of the vitamin K-dependent gamma-carboxylase alone.
Cell death in the colonic epithelium during inflammatory bowel diseases (2010)

CD95 is a member of the death receptor family. It is a prototypical inducer of apoptosis that, upon binding of its cognate ligand (CD95L), forms a death-inducing signaling complex composed of adaptor molecules and initiator caspases that transmit the apoptosis signal. The CD95/CD95L system was implicated in the etiology of inflammatory bowel disease (IBD) based, primarily, on the finding that CD95 is highly expressed in the intestinal epithelial cells and that epithelial apoptosis is increased in IBD. In recent years it has been recognized that CD95, while playing an important role as an apoptosis-inducing receptor in the immune system, also has multiple nonapoptotic functions on nonimmune cells. This review critically discusses the data on the possible function of CD95 as an apoptosis-inducing receptor in IBD and discusses alternative mechanisms for epithelial cell loss in IBD.
Elevated expression of pp60c-src in low grade human bladder carcinoma. (1992)

The results presented in this report demonstrate that the tyrosine-specific protein kinase activity of pp60c-src is elevated over that recorded in normal bladder mucosa in a subset of human bladder carcinomas. Increased kinase activity was observed mainly in low grade bladder lesions and was associated, at least in part, with elevated levels of pp60c-src expression. Extension of this analysis to a panel of human bladder carcinoma cell lines confirmed previous observations of low pp60c-src kinase activity in three lines established from high grade (GIII) bladder tumors and revealed increased kinase activity in three alternative bladder lines derived from GI or GII tumors. Use of an anti-phosphotyrosine antibody in Western blot analysis revealed the presence of novel phosphotyrosyl cellular substrates in human bladder cell lines and tumors displaying elevated pp60c-src kinase activity. These observations suggest an association for the src protooncogene in urothelial cell differentiation events.
Expression patterns of claudin family of tight junction membrane proteins in developing mouse submandibular gland (2004)

Here, we investigated the expression of the claudin family of tight junction transmembrane proteins in the developing mouse submandibular gland. Data obtained by reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence microscopy showed the expression and localization of claudin-3 to -8, -10, and -11 at epithelial tight junctions. Examination of the glands taken from embryonic day (E) 14, E16, and newborn mice revealed differential expression patterns of these claudins in the developing epithelium. Claudin-3, -5, and -7 were expressed in all of the luminal epithelial cells of the ducts at all of the developmental stages examined and in those of terminal tubules at E16 and later. Claudin-4 was expressed mainly in the ducts at all the developmental stages. The expression of claudin-6 and -8 was also restricted to the ducts at E14 and E16; but after birth, the former was undetectable, whereas the latter was expressed in both the ducts and terminal tubules. Claudin-10 and -11 were detectable mainly in the terminal tubules at E16 and later. In addition to being found in the epithelium, claudin-5 was also expressed in certain mesenchymal cells, probably endothelial cells. These results will provide a valuable resource for further investigation of tubulogenesis and physiological regulation of claudin-based tight junctions.