gebhart/patrepeval huggingface dataset:
Identification of a positive regulatory element responsible for tissue-specific expression of prostate-specific antigen. (1997)

The prostate-specific antigen (PSA) promoter (PSA-P) has been identified, characterized, and determined to be tissue specific. Compared with high expression of the genomic PSA gene in prostate cells, expression of the transgene driven by the putative PSA promoter is low. This suggests that the identified promoter may be incomplete or may function optimally with additional regulatory elements. To identify the presence of additional regulatory elements, we screened sequences upstream of the PSA promoter and identified a DNA fragment of 822 bp, which enhances PSA gene expression. Combining the newly identified PSA gene regulatory sequence (PSAR) with our previously identified PSA promoter (PCPSA-P) exhibited enhanced expressional activity in the PSA-producing LNCaP cell line. With the addition of 10 to 100 nM dihydrotestosterone, a more than 1000-fold increase in expression was observed as compared to androgen-negative controls. Furthermore, although the combined regulatory element (PSAR)-PSA promoter (PCPSA-P) sequence resulted in high transgene expression in LNCaP cell lines, the combined regulatory element-promoter sequence resulted in minimal expression in the non-PSA-producing prostate cell line PC-3, renal tumor cell line R11, and cervical adenocarcinoma cell line HeLa. The newly identified 822 bp alone could also function as a promoter. Compared with the combined promoter, however, the 822-bp fragment alone demonstrated lower activity and lower responsiveness to androgen stimulation. Our results suggest that coupling the PSA promoter with an upstream regulatory element results in a marked increase in PSA expression, suggesting that the complete PSA promoter contains two functional domains: a proximal promoter and a distal promoter, which can also function as an enhancer. The enhanced gene expression of the new construct, combined with its tissue specificity and androgen responsiveness, in turn provides a foundation for the development of tissue-specific vectors for prostate cancer gene therapy.
Effects of ascorbic acid on Chlamydia trachomatis infection and on erythromycin treatment in primary cultures of human amniotic cells (1992)

Ascorbic acid (vitamin C) is an essential nutrient for humans. It may also be needed by Chlamydia trachomatis, an intracellular bacterium. We investigated the effects of vitamin C on the growth of C. trachomatis E/UW-5/Cx in a primary culture of human amniotic epithelial cells. The results showed that vitamin C enhances C. trachomatis infection at concentrations of 0.2, 0.6, and 1.2 mg/dl (P less than 0.001). These three concentrations represent the in vivo concentrations of deficiency, normal, and overload levels in serum, respectively. The enhancement was dose dependent. However, the growth of C. trachomatis was inhibited at vitamin C concentrations of 120 and 1,200 mg/dl. The inhibitory effect of erythromycin against C. trachomatis was shown to be reduced in the presence of vitamin C at the three concentrations tested (P less than 0.025-0.001), and MICs were four times greater (1.6 versus 0.4 micrograms/ml). Human amniotic cells were tolerant to vitamin C concentrations of up to 1,200 mg/dl. The results show that vitamin C may be an important nutrient for C. trachomatis and that incorporation of vitamin C in the culture medium may enhance the isolation and propagation of C. trachomatis in cell cultures.
Cation Transport Across Cultured Trophoblast Membrane in Preeclampsia (1992)

Cation transport across blood cell membrane is altered during hypertensive pregnancy. Since this finding has been reported using different cell lines, we aimed to assess the activity of carrier enzymes in vitro in cultured trophoblast cells. Cells from six normotensive and six preeclamptic patients were cultured, and Na+/K+-ATPase, Ca++-ATPase activities, and cytosolic free calcium were measured immediately after preparation and after 8 and 24 hours. Na+/K+-ATPase activity was reduced, Ca++-ATPase activity and cytosolic free Ca++ increased in trophoblastic cells from preeclamptic patients, compared to the normotensive.After 8 hours both the enzymatic activities and the free calcium concentration increased in both groups. After 24 hours no significant difference was found in both Ca++-ATPase activity and free calcium between trophoblast cells from preeclamptic and normotensive women, whereas Na+/K+-ATPase activity in trophoblast from preeclamptic women remained reduced compared to that observed in cells from normotensive women. These results indicate that the altered enzyme activity in preeclampsia may be caused by different mechanisms: Ca++-ATPase may be sensitive to changes in cell microenvironment, whereas Na+/K+ATPase could undergo intrinsic structural changes.
Purification and Concentration of DNA from Aqueous Solutions (1998)

Abstract This unit presents procedures for manipulating solutions of single‐ or double‐ stranded DNA through purification and concentration steps. These techniques are useful when proteins or solute molecules need to be removed from aqueous solutions, or when DNA solutions need to be concentrated. The basic protocol, using phenol extraction and ethanol (or isopropanol) precipitation, is appropriate for the purification of DNA from small volumes (&lt;0.4 ml) at concentrations lower than 1 mg/ml. Three support protocols outline methods to buffer the phenol used in extractions, concentrate DNA using butanol, and extract residual organic solvents with ether. An alternative to these methods is nucleic acid purification using glass beads and this is also presented. These protocols may also be used for purifying RNA. Two alternate protocols can be used for concentrating RNA and extracting and precipitating DNA from larger volumes and from dilute solutions, and for removing low molecular weight oligonucleotides and triphosphates.
Deeply penetrating photoacoustic tomography in biological tissues enhanced with an optical contrast agent (2005)

Photoacoustic tomography (PAT) in a circular scanning configuration was developed to image deeply embedded optical heterogeneity in biological tissues. While the optical penetration was maximized with near-infrared laser pulses of 800-nm wavelength, the optical contrast was enhanced by Indocyanine Green (ICG) dye whose absorption peak matched the laser wavelength. This optimized PAT was able to image objects embedded at depths of as much as 5.2 cm, 6.2 times the 1/e optical penetration depth, in chicken breast muscle at a resolution of <780 microm and a sensitivity of <7 pmol of ICG in blood. The resolution was found to deteriorate slowly with increasing imaging depth. The effects of detection bandwidth on the quality of images acquired simultaneously by four different ultrasonic transducers are described.
Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report (2017)

High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the influence of baseline total metabolic tumor volume (TMTV<sub>0</sub>) on rituximab PK and of TMTV<sub>0</sub> and rituximab exposure on outcome in patients with diffuse large B-cell lymphoma (DLBCL). TMTV<sub>0</sub> was measured by <sup>18</sup>F-fluorodeoxyglucose-positron emission tomography-computed tomography in 108 previously untreated DLBCL patients who received four 375 mg/m<sup>2</sup> rituximab infusions every 2 weeks in combination with chemotherapy in 2 prospective trials. A 2-compartment population model allowed describing rituximab PK and calculating rituximab exposure (area under the concentration-time curve; AUC). The association of TMTV<sub>0</sub> and AUC with metabolic response after 4 cycles, as well as progression-free survival (PFS) and overall survival (OS), was assessed using logistic regression and Cox models, respectively. Cutoff values for patient outcome were determined using receiver operating characteristic curve analysis. Exposure to rituximab decreased as TMTV<sub>0</sub> increased (<i>R</i><sup>2</sup> = 0.41, <i>P</i> < .0001). A high AUC in cycle 1 (≥9400 mg × h per liter) was associated with better response (odds ratio, 5.56; <i>P</i> = .0006) and longer PFS (hazard ratio [HR], 0.38; <i>P</i> = .011) and OS (HR, 0.17; <i>P</i> = .001). A nomogram for rituximab dose needed to obtain optimal AUC according to TMTV<sub>0</sub> was constructed, and the 375 mg/m<sup>2</sup> classical dose would be suitable for patients with TMTV<sub>0</sub> <281 cm<sup>3</sup> In summary, rituximab exposure is influenced by TMTV<sub>0</sub> and correlates with response and outcome of DLBCL patients. Dose individualization according to TMTV<sub>0</sub> should be evaluated in prospective studies. These studies were registered at www.clinicaltrials.gov as #NCT00498043 and #NCT00841945.
Prediction of protein function from protein sequence and structure (2003)

The sequence of a genome contains the plans of the possible life of an organism, but implementation of genetic information depends on the functions of the proteins and nucleic acids that it encodes. Many individual proteins of known sequence and structure present challenges to the understanding of their function. In particular, a number of genes responsible for diseases have been identified but their specific functions are unknown. Whole-genome sequencing projects are a major source of proteins of unknown function. Annotation of a genome involves assignment of functions to gene products, in most cases on the basis of amino-acid sequence alone. 3D structure can aid the assignment of function, motivating the challenge of structural genomics projects to make structural information available for novel uncharacterized proteins. Structure-based identification of homologues often succeeds where sequence-alone-based methods fail, because in many cases evolution retains the folding pattern long after sequence similarity becomes undetectable. Nevertheless, prediction of protein function from sequence and structure is a difficult problem, because homologous proteins often have different functions. Many methods of function prediction rely on identifying similarity in sequence and/or structure between a protein of unknown function and one or more well-understood proteins. Alternative methods include inferring conservation patterns in members of a functionally uncharacterized family for which many sequences and structures are known. However, these inferences are tenuous. Such methods provide reasonable guesses at function, but are far from foolproof. It is therefore fortunate that the development of whole-organism approaches and comparative genomics permits other approaches to function prediction when the data are available. These include the use of protein-protein interaction patterns, and correlations between occurrences of related proteins in different organisms, as indicators of functional properties. Even if it is possible to ascribe a particular function to a gene product, the protein may have multiple functions. A fundamental problem is that function is in many cases an ill-defined concept. In this article we review the state of the art in function prediction and describe some of the underlying difficulties and successes.
Generation of Replication-Competent Recombinant Influenza A Viruses Carrying a Reporter Gene Harbored in the Neuraminidase Segment (2010)

Replication-competent influenza viruses carrying reporter genes are of great use for basic research, screening of antiviral drugs, and neutralizing of antibodies. In this study, two recombinant influenza A viruses with a neuraminidase (NA) segment harboring enhanced green fluorescent protein (EGFP) in the background of A/PR/8/34 (PR8) were generated. The viral RNA (vRNA)-specific packaging signals for NA were largely retained for efficient packaging. An "autocleave" 2A peptide sequence, which was inserted at the N terminus or the COOH terminus of NA to link with EGFP, enabled NA and EGFP to be expressed monocistronically. Further analysis demonstrated that both viruses, named rPR8-EGFP+NA and rPR8-NA+EGPF, although with some characteristic differences in growth and EGFP expression, could replicate in noncomplementary cells and propagate to large quantities while maintaining genome stability after multiple passages in embryonated eggs. These replication-competent influenza viruses carrying reporter genes are a great addition to the tool set for developing antiviral therapeutics and vaccines and for in vivo studies of viral dissemination and pathogenicity.
Role of gamma interferon and tumor necrosis factor alpha in resistance to Salmonella typhimurium infection (1992)

In mice infected with a sublethal dose of Salmonella typhimurium, the injection of an anti-gamma interferon (IFN-gamma) monoclonal antibody increased bacterial proliferation in the spleen and led to death on day 7 or 8. Depletion of both CD4+ and CD8+ T cells with monoclonal antibodies in vivo had a much less marked effect during the first week of infection than the administration of anti-IFN-gamma antibodies, suggesting that cells other than T lymphocytes participate in the production of IFN-gamma at this time. Administration of anti-tumor necrosis factor alpha (TNF-alpha) antibodies to mice infected with a sublethal dose of S. typhimurium induced the same effect as anti-IFN-gamma antibodies, while the administration of both antibodies resulted in a synergistic interaction. When mice were infected with an avirulent strain of S. typhimurium and challenged on day 7 either with a virulent strain of S. typhimurium or with Listeria monocytogenes, their resistance to reinfection was slightly depressed by anti-IFN-gamma or anti-TNF-alpha antibodies given 1 day before challenge and much more strongly depressed by the simultaneous administration of both antibodies. Taken together, these results indicate that IFN-gamma and TNF-alpha play an essential role in acquired resistance during the early phase of S. typhimurium infection.
Regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril and the expression of contractile proteins. (1990)

Several experimental models involving the development of cardiac hypertrophy in adult rats are characterized by the reexpression of the fetal isoform of myosin heavy chain (V3). To determine whether a similar adult-to-fetal shift in the expression of the thin-filament proteins occurs during cardiac hypertrophy, we have examined the expression of the isoforms of myosin, tropomyosin, and troponin T in the left ventricle of young spontaneously hypertensive rats (SHR) with and without treatment using enalapril, an angiotensin converting enzyme inhibitor. Phosphorylation of tropomyosin, which is predominant in the fetal state, was also analyzed. Twelve-week-old SHR were treated with enalapril for 2, 5, 8, and 9 weeks followed by withdrawal of treatment for 9 weeks. Control SHR, without drug treatment, were weight- and age-matched. After 9 weeks of enalapril treatment, mean arterial blood pressure was reduced (from 166 +/- 11 to 89 +/- 5 mm Hg), and left ventricular weight/body weight ratio was regressed (from 2.53 +/- 0.14 to 1.96 +/- 0.05 g/kg) to normotensive levels. During the 9-week treatment period, the percent V3 decreased in SHR substantially from 35 +/- 3% to 13 +/- 1%. There was a significant correlation between the left ventricular hypertrophy and the percent V3 myosin expression in the SHR during regression (r = 0.697, p less than 0.001). However, only the adult isoforms of tropomyosin and troponin T were detected in the SHR with or without enalapril treatment, and the level of tropomyosin phosphorylation remained constant irrespective of the degree of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Schedule-Dependent Cytotoxic Synergism of Pemetrexed and Erlotinib in Human Non–Small Cell Lung Cancer Cells (2007)

The combination of pemetrexed and erlotinib is synergistic in NSCLC in vitro if exposure to erlotinib before pemetrexed is avoided, particularly in tumors that are sensitive to erlotinib. Based on these findings, a randomized phase II study comparing the progression-free survival between an intermittent combination of erlotinib and pemetrexed (experimental arm) and pemetrexed alone (control arm) in patients with relapsing NSCLC has been initiated.
Structural Underpinnings of the Enhanced Cycling Stability upon Al-Substitution in LiNi0.45Mn0.45Co0.1–yAlyO2 Positive Electrode Materials for Li-ion Batteries (2012)

Single-phase LiNi0.45Mn0.45Co0.1–yAlyO2 layered oxide materials with 0 ≤ y ≤ 0.10 were prepared using the glycine-nitrate combustion method. Al-substitution has a minimal effect on the defect concentration and rate capability of the materials, but raises the operating voltage and reduces the capacity fade of the materials during prolonged cycling compared to the unsubstituted system. In situ X-ray diffraction suggests the presence of Al has a significant structural impact during battery operation. It acts to limit the changes in lattice parameters observed during electrochemical charging and cycling of the materials. High-resolution X-ray diffraction reveals structural distortions in the transition metal layers of as-synthesized powders with high Al-contents, as well as a structural evolution seen in all materials after cycling.
Comparison of dermal substitutes in wound healing utilizing a nude mouse model. (2005)

Integra elicited the greatest foreign body response. Although the Dermalogen group had the thickest elastin fiber fragments, Dermagraft may have initiated the earliest elastin fiber formation in the wounds. While all dermal substitutes were incorporated into the wound bed and wound contracture was decreased, acellular dermal matrix and Alloderm, both human skin-derived products, produced less contraction and the thickest new "dermis" in the healed wounds compared to the control or synthetic dermal substitutes.
[Anti-cancer treatment with prostaglandin synthetase inhibitor in animal models]. (1986)

Carcinomas produce elevated quantities of prostaglandins (PGs), particularly the E series, which can play an important role in the suppression of the cellular immune reaction in tumor-bearing individuals. These findings have raised the possibility that PG synthetase inhibitor can restore the immune activity against tumors. The anti-tumor activity of indomethacin, a potent PG synthetase inhibitor, was investigated in mice implanted with colon carcinoma 38, colon carcinoma 26 and Lewis lung carcinoma in a series of model studies for cancer treatment in man. Treatment with indomethacin substantially reduced the levels of PGs, particularly PGE2 in tumor tissue, inhibited the tumor growth, particularly the early stage of cell proliferation, prolonged the survival time, eliminated tumors in the abdominal cavity, and inhibited metastatic tumor recurrence after surgery. Also, the treatment reduced the growth of human gastric and colon carcinomas transplanted into nude mice. Thus, indomethacin might also be effective against human carcinomas. It is postulated that PG synthetase inhibitor may prove to be a good therapeutic tool effective against human cancer when used in combination with chemotherapeutic and other immunotherapeutic drugs as well as with low-dose radiation therapy.
Cloning, Expression, and Functional Characterization of Secondary Amino Acid Transporters of Lactococcus lactis (2012)

Fourteen genes encoding putative secondary amino acid transporters were identified in the genomes of Lactococcus lactis subsp. cremoris strains MG1363 and SK11 and L. lactis subsp. lactis strains IL1403 and KF147, 12 of which were common to all four strains. Amino acid uptake in L. lactis cells overexpressing the genes revealed transporters specific for histidine, lysine, arginine, agmatine, putrescine, aromatic amino acids, acidic amino acids, serine, and branched-chain amino acids. Substrate specificities were demonstrated by inhibition profiles determined in the presence of excesses of the other amino acids. Four knockout mutants, lacking the lysine transporter LysP, the histidine transporter HisP (formerly LysQ), the acidic amino acid transporter AcaP (YlcA), or the aromatic amino acid transporter FywP (YsjA), were constructed. The LysP, HisP, and FywP deletion mutants showed drastically decreased rates of uptake of the corresponding substrates at low concentrations. The same was observed for the AcaP mutant with aspartate but not with glutamate. In rich M17 medium, the deletion of none of the transporters affected growth. In contrast, the deletion of the HisP, AcaP, and FywP transporters did affect growth in a defined medium with free amino acids as the sole amino acid source. HisP was essential at low histidine concentrations, and AcaP was essential in the absence of glutamine. FywP appeared to play a role in retaining intracellularly synthesized aromatic amino acids when these were not added to the medium. Finally, HisP, AcaP, and FywP did not play a role in the excretion of accumulated histidine, glutamate, or phenylalanine, respectively, indicating the involvement of other transporters.
Analysis Techniques for SIMD Machine Interconnection Networks and the Effects of Processor Address Masks (1977)

Various techniques for evaluating and comparing interconnection networks for SIMD machines are presented. These techniques are demonstrated by using them to analyze the networks that have been proposed in the literature. The model of SIMD machines used in the first part of the paper requires all data transfers between processing elements to be representable as permutations on the processing element addresses. We use the theory of permutation groups to aid in the analysis of the cycle structures of the different interconnection networks and discuss the importance of the cycle structure to the SIMD machine architect. A processing element address masking scheme, to determine which processing elements will be active, is introduced. The effects of this masking system when used with different networks are examined. Model independent techniques for proving lower bounds on the time required for a network to simulate a particular interconnection are presented. These techniques are used to prove a lower time bound on the simulation of each network by each of the other networks.
Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus (2006)

The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: the ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.
Differential regulation of hepatocyte-enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells. (1991)

To investigate the regulation of genes whose expression is enriched in liver we studied expression of the albumin and transthyretin (TTR) genes in a series of rat hepatoma cell lines (FaO, C2, C2rev7, and H5) that express these genes at different rates. The level of expression of albumin and TTR was compared to the expression and DNA-binding activity of four transcription factors, HNF1/LFB1, C/EBP, HNF3, and HNF4, that are found at high concentrations in liver. We conclude that the levels of these factors are controlled both transcriptionally (HNF-3, HNF-4, and C/EBP) and post-transcriptionally (HNF-1/LFB1), and that the cellular concentration of these DNA-binding proteins helps explain the level of transcriptional activity observed for the genes they regulate.