gebhart/patrepeval huggingface dataset:
Synthesis and Anti-HIV-1 Activity of Novel 2,3-Dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones (1998)

Appropriately substituted 2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones 9-12 and 18 were considered as annulated analogues of HEPT (1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine), and some of these compounds were also found active against HIV-1, the most active one being 2,3-dihydro-5-[(3,5-dimethylphenyl)methyl]-3-ethoxy-6-ethyl-7H- thiazolo[3,2-a]pyrimidin-7-one (10b). S-Alkylation of 5-alkyl-6-(arylmethyl)-2-thiouracils 1-4 was performed with 2-bromoacetaldehyde acetals to furnish the S-[bis(alkoxy)ethyl] derivatives 5-8 and with allyl bromide to furnish S-allyl derivatives 17. The target compounds 9-12 were obtained by an N1 regioselective intramolecular cyclization reaction of silylated 5-8 using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the catalyst. Treatment of the S-allyl derivatives 17 with bromine in dry methylene chloride afforded the 3-(bromomethyl) derivatives 18.
Epitopes of the HIV-1-Negative Factor ( nef ) Reactive with Murine Monoclonal Antibodies and Human HIV-1-Positive Sera (1991)

Murine monoclonal antibodies (MAbs) raised against a recombinant nef protein fragment of human immunodeficiency virus type 1 (HIV-1) strain BH10 were characterized by an epitope mapping system using overlapping decapeptides. Four different immunogenic regions were identified. Ten human HIV-1-positive sera were tested in the same epitope mapping system, seven of these were reactive with four immunogenic regions. Two of the nef-specific epitopes recognized by human sera overlapped with the epitopes defined by the murine monoclonal antibodies. The reactivity of the monoclonal antibodies with the recombinant nef protein and with infected and uninfected cells were investigated in a variety of test systems. The results are discussed with respect to homologous regions of nef and cellular proteins.
Statistical timing for parametric yield prediction of digital integrated circuits (2003)

Uncertainty in circuit performance due to manufacturing and environmental variations is increasing with each new generation of technology. It is therefore important to predict the performance of a chip as a probabilistic quantity. This paper proposes three novel algorithms for statistical timing analysis and parametric yield prediction of digital integrated circuits. The methods have been implemented in the context of the EinsTimer static timing analyzer. Numerical results are presented to study the strengths and weaknesses of these complementary approaches. Across-the-chip variability continues to be accommodated by EinsTimer's "Linear Combination of Delay (LCD)" mode. Timing analysis results in the face of statistical temperature and Vdd variations are presented on an industrial ASIC part on which a bounded timing methodology leads to surprisingly wrong results.
Trypanothione is the primary target for arsenical drugs against African trypanosomes. (1989)

The trypanosomatid metabolite N1,N8-bis-(glutathionyl)spermidine (trypanothione) has been demonstrated to form a stable adduct with the aromatic arsenical drug melarsen oxide [p-(4,6-diamino-s-triazinyl-2-yl)aminophenyl arsenoxide]. The stability constant of the melarsen-trypanothione adduct (Mel T) has been determined to be 1.05 x 10(7) M-1. When bloodstream Trypanosoma brucei are incubated with either melarsen oxide or the 2,3-dimercaptopropanol adduct of melarsen oxide (melarsoprol), Mel T is the only arsenical derivative detectable in acid-soluble extracts of the cells. Trypanothione may therefore be regarded as a primary target for aromatic arsenical derivatives against African trypanosomes. The selective toxic action of these compounds might arise through sequestration of intracellular trypanothione in the form of Mel T, or Mel T itself may be toxic within the cell. The latter possibility is illustrated by the finding that Mel T is an inhibitor of trypanothione reductase from T. brucei (Ki = 9.0 microM)--an enzyme that is central to the regulation of the thiol/disulfide redox balance in the parasite and absent from the host.
Supercomputing for the parallelization of whole genome analysis (2014)

The MegaSeq workflow is designed to harness the size and memory of the Cray XE6, housed at Argonne National Laboratory, for whole genome analysis in a platform designed to better match current and emerging sequencing volume.
Utilization of Natural Fucosylated Oligosaccharides by Three Novel α- l -Fucosidases from a Probiotic Lactobacillus casei Strain (2010)

Three putative α-L-fucosidases encoded in the Lactobacillus casei BL23 genome were cloned and purified. The proteins displayed different abilities to hydrolyze natural fucosyloligosaccharides like 2'-fucosyllactose, H antigen disaccharide, H antigen type II trisaccharide, and 3'-, 4'-, and 6'-fucosyl-GlcNAc. This indicated a possible role in the utilization of oligosaccharides present in human milk and intestinal mucosa.
Ofatumumab, a Novel Anti-CD20 Monoclonal Antibody for the Treatment of B-Cell Malignancies (2010)

The availability of safe and effective monoclonal antibodies (mAbs) has dramatically altered treatment strategies for B-cell malignancies. Rituximab, a type I chimeric anti-CD20 mAb, not only has activity against a broad range of CD20-positive B-cell malignancies but also, when combined with chemotherapy or other biologic agents, has improved response rates; in addition, in certain situations, progression-free survival and even overall survival may be prolonged. Recently, other anti-CD20 mAbs have been developed to improve on the activity achieved with rituximab or to demonstrate efficacy in patients whose diseases are resistant to rituximab. The most extensively studied of these is ofatumumab, a type I human antibody that binds to a different epitope of CD20 than rituximab. Preclinical data suggest improved complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity compared with rituximab. In early clinical trials, ofatumumab demonstrated single-agent activity against chronic lymphocytic leukemia (CLL) and a number of histologies of B-cell non-Hodgkin's lymphomas. This antibody was recently approved by the US Food and Drug Administration for the treatment of CLL that is resistant to both fludarabine and alemtuzumab. Additional study is ongoing with ofatumumab in combination with chemotherapy and biologic agents to further enhance its efficacy. Ofatumumab offers another effective agent with which to improve the outcome of patients with B-cell malignancies.
Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: The evolution from myeloablative to lymphoablative transplant regimens (2006)

While autologous HSCT appears to induce remissions and improve quality of life in the majority of patients, it remains unclear whether either myeloablative or lymphoablative autologous HSCT can cure autoimmune disorders, and randomized controlled trials are needed to confirm the benefit and cost-effectiveness of this therapy. There are currently 2 disparate philosophical approaches to the design of these trials. One approach is to apply aggressive malignancy-specific myeloablative regimens. Although more intensive lymphoablative regimens could be designed, since cancer-specific myeloablative regimens are more intensive than currently utilized lymphoablative regimens, myeloablative regimens may result in longer duration of disease remission. The other philosophical approach is to use lymphoablative regimens that are disease specific and nonmyeloablative (i.e., do not irreversibly damage the hematopoietic stem cell compartment), maximize drugs already used to treat each disease, and avoid agents in the regimen that could cause further damage to already disease-injured organs. It appears that lymphoablative regimens are safer than myeloablative regimens, and it appears that even if relapse occurs, durable long-term remission may be achieved with conventional treatment to which the patient's disease was previously refractory. If considered on a disease-specific basis, the high disease-related mortality of SSc could justify the higher treatment-related mortality associated with a myeloablative regimen. However, since radiation is already considered a relative contraindication for SSc and radiation-induced and SSc-related microvascular compartment injuries are similar, and because TBI is associated with late myelodysplasia, leukemia, and lymphomas, some investigators have voiced concern over use of a TBI-based myeloablative regimen to treat SSc (19,59). The controversy that surrounds the competing visions of lymphoablative versus myeloablative autologous HSCT regimens for autoimmune disease has yet to be resolved. Further experience will likely indicate the superiority of one of these approaches when both safety and efficacy are considered. Since both lymphoablative and myeloablative protocols are being offered for a select group of severely ill patients with autoimmune disorders refractory to conventional therapy, subspecialists who refer patients for such therapy should be aware of the emerging body of literature that at the very least suggests that lymphoablative regimens will be associated with less morbidity and mortality. Sharing of such information is crucial if patients are to provide consent that is truly informed.
Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations (2007)

High resolution array CGH allowed us to identify copy number changes in 100% of the primary MM samples. We segregated different MM subgroups based on their genomic profiles which made it possible to identify homozygous deletions and amplifications of great genetic relevance in MM.
The capped U6 small nuclear RNA is transcribed by RNA polymerase III. (1987)

U6 RNA is an abundant, capped, small nuclear RNA (snRNA) species associated with heterogeneous nuclear ribonucleoproteins in eukaryotic cells. U4 RNA and U6 RNA are hydrogen bonded in a 1:1 ratio in discrete small nuclear ribonucleoprotein particles that are required in pre-mRNA processing. Previous reports have established that the mRNAs and U1 to U5 U-snRNAs are synthesized by RNA polymerase II. Evidence is presented here for synthesis of U6 RNA by RNA polymerase III. The synthesis of U6 RNA in vitro, using Novikoff hepatoma or HeLa whole cell extracts, was not inhibited at low (1 microgram/ml) concentrations of alpha-amanitin, and only 35% inhibition occurred at 10 micrograms/ml concentration. The in vitro synthesized U6 RNA, like other RNA polymerase III transcripts, was associated with La antigen. The U6 RNA synthesized in vitro by the whole cell extracts was capped, but no other internal post-transcriptional modifications were found. Uridylic acid residues were also added post-transcriptionally to the 3'-end of U6 RNA in vitro. U6 RNA, though capped on its 5'-end, is transcribed by RNA polymerase III; this is the first report of a capped RNA molecule synthesized by RNA polymerase III.
Graft-versus-Host Disease Prevents the Maturation of Plasmacytoid Dendritic Cells (2009)

The role of Ag presenting cell subsets in graft-versus-host disease (GVHD) remains unclear. We have thus examined the ability of plasmacytoid dendritic cells (pDC) to modulate transplant outcome. Surprisingly, host pDC were exquisitely sensitive to total body irradiation and were depleted before transplantation, thus allowing us to focus on donor pDC [corrected]. The depletion of all pDC from bone marrow grafts resulted in an acceleration of GVHD mortality while the depletion of mature pDC from G-CSF mobilized splenic grafts had no effect. Thus, donor bone marrow pDC, but not mature pDC contained within stem cell grafts attenuate acute GVHD. In the presence of GVHD, donor pDC completely failed to reconstitute although a CD11clow120G8+ precursor DC reconstituted in an exaggerated and transient manner. These cells expressed Flt-3, the macrophage colony stimulating factor receptor and, consistent with a common dendritic cell (DC) precursor, were capable of differentiation into pDC and conventional DC in vivo in the absence of GVHD. These precursors were MHC class II+ and CD80/86+ but lacked CD40, were actively presenting host Ag and inhibited GVHD and T cell proliferation in a contact-dependent fashion. These data demonstrate that GVHD prevents the maturation of pDC and instead promotes the generation of a suppressive precursor DC, further contributing to the state of immune paralysis after transplantation.
An improved method to determine cell viability by simultaneous staining with fluorescein diacetate-propidium iodide. (1985)

A rapid, simultaneous double-staining procedure using fluorescein diacetate (FDA) and propidium iodide (PI) is described for use in the determination of cell viability in cell suspension. Air-dried slide preparations can be made from the cell suspensions so that an accurate estimate of the viability of the cells in the original suspension can be made up to 1 week later. Viable cells fluoresce bright green, while nonviable cells are bright red. Furthermore, when FDA-PI staining is compared to trypan blue dye exclusion as a method to determine cell viability, FDA-PI is found to be more consistent over prolonged periods of exposure to the dyes. Therefore, double staining with FDA-PI is a rapid, convenient, and reliable method to determine cell viability.
Portal dosimetry for pretreatment verification of IMRT plan: a comparison with 2D ion chamber array (2010)

Portal dosimetry (PD) was performed for 181 fields from 14 IMRT plans of various clinical sites at gantry zero and source-to-detector distance (SDD) of 100 cm. PD was realized using aSi1000 electronic portal imaging device (EPID) and portal dose prediction (PDP) algorithm implemented in Eclipse treatment planning system (TPS). Agreement of PDP predicted and EPID measured photon fluence/dose distribution were evaluated using gamma (γ) index set at 3% at 3 mm distance to point agreement (DTA). Three gamma scaling parameters, maximum γ (γ(max)), average γ (γ(avg)) and percentage of points with γ ≤ 1 (γ% ≤ 1) were estimated for each field. An independent measurement was carried out using MatriXX 2D ion chamber array with detector plane at 100 cm and γ(max), γ(avg) and γ% ≤ 1 were estimated using OmniPro IMRT analyzing software. Effect of extended SDD and gantry rotation on portal dosimetry outcome was also investigated for another 45 IMRT fields. PDP predicted and EPID measured photon fluence agrees well with overall mean values of γ(max), γ(avg) and γ% ≤ 1 at 2.02, 0.24 and 99.43%, respectively. γ(max) value was lower in 15 MV compared to 6 MV IMRT plan. Independent verification using MatriXX showed comparable overall mean values of γ(avg) and γ% ≤ 1 at 0.25 and 99.80%. However, in all plans, MatriXX showed significantly lower γ(max) (p < 0.05) with an overall mean value of 1.35. In portal dosimetry, compared to gamma values at 100 cm SDD, γ(max), γ(avg) and γ% ≤ 1 values improve from a mean of 0.16, 0.03 and 0.26 at 110 cm SDD to 0.35, 0.05 and 0.29 at 140 cm SDD. PD outcome was independent of gantry rotation. In conclusion, both MatriXX 2D ion chamber array and portal dosimetry showed comparable results and can be use as an alternative to each other for relative photon fluence verification.
Salt Tolerance Conferred by Overexpression of a Vacuolar Na + /H + Antiport in Arabidopsis (1999)

Agricultural productivity is severely affected by soil salinity. One possible mechanism by which plants could survive salt stress is to compartmentalize sodium ions away from the cytosol. Overexpression of a vacuolar Na+/H+ antiport from Arabidopsis thaliana in Arabidopsis plants promotes sustained growth and development in soil watered with up to 200 millimolar sodium chloride. This salinity tolerance was correlated with higher-than-normal levels of AtNHX1 transcripts, protein, and vacuolar Na+/H+ (sodium/proton) antiport activity. These results demonstrate the feasibility of engineering salt tolerance in plants.
Phase II Trial of the Combination of Paclitaxel and 5-Fluorouracil in the Treatment of Advanced Gastric Cancer (1999)

This prospective phase II clinical trial was performed to explore the activity and efficacy of the combination of paclitaxel and 5-fluorouracil in the treatment of advanced gastric adenocarcinoma. Thirty-one patients ages 18 to 70 years, with Karnofsky performance status (KPS) >50, adequate cardiac, renal, and hepatic functions, measurable metastatic or locally unresectable disease, life expectancy > or =3 months, signed written informed consent, and without any previous chemotherapy were assigned to receive on an outpatient basis: paclitaxel--175 mg/m2, in a 3-hour infusion on day 1 and 5-fluorouracil--1.5 g/m2, also in a 3-hour infusion on day 2 every 21 days, for a maximum of seven cycles. A system to assess clinical benefit based on KPS, analgesic consumption, and weight gain was also used in this trial. Median age was 61 years (range, 31-70 years). The 29 patients eligible for response and toxicity evaluation underwent 147 cycles of chemotherapy. There were 19 (65.5%) objective responses (95% confidence interval: 48%-83%), including 7 (24.1%) complete responses and 12 (41.4%) partial responses. Three patients had the complete response pathologically confirmed. In three of six patients who went to second-look laparotomy, a potentially curative esophagogastrectomy was possible. The toxicity of this combination was considered low, predictable, and manageable and was characterized mainly by reversible alopecia, peripheral neuropathy, myalgia, and mild neutropenia. Fifteen (51.7%) patients attained a clinical benefit response. The median overall survival was 12 months (range, 2-30+ months) and the 30-month overall survival was 20%. This novel regimen appears to be very effective in advanced gastric cancer. The projected 2-year survival of 20% is higher than that achieved with other first-line regimens. These encouraging results indicate the need for further studies to confirm the merit of this regimen.
Expression in Escherichia coli and sequence analysis of the listeriolysin O determinant of Listeria monocytogenes (1988)

To evaluate the role of hemolysin production in the virulence of Listeria monocytogenes, we have undertaken the analysis of the chromosomal region containing hlyA, the gene coding for listeriolysin O. A recombinant cosmid, conferring a hemolytic phenotype to Escherichia coli, was shown to express listeriolysin O, by immunoblotting with a specific antiserum against listeriolysin O. The presence of hlyA on the cosmid was demonstrated by DNA hybridization with a probe previously shown to contain part of hlyA. The complete nucleotide sequence of hlyA has been determined. The deduced protein sequence reveals the presence of a putative 25-amino-acid signal sequence: the secreted form of listeriolysin O would have 504 amino acids, in agreement with the molecular weight of purified listeriolysin O (58,000). The protein sequence is highly homologous to those of streptolysin O and pneumolysin. A peptide of 11 amino acids conserved in the three proteins contains the unique cysteine known to be essential for lytic activity. By DNA-DNA hybridization, the listeriolysin O gene was detected in all L. monocytogenes strains tested, even in the nonhemolytic type strain. The gene was absent in other species of the genus Listeria.
A protease activity associated with acetylcholinesterase releases the membrane-bound form of the amyloid protein precursor of Alzheimer's disease (1991)

Amyloid deposits in the brains of patients with Alzheimer's disease (AD) contain a protein (beta A4) which is abnormally cleaved from a larger transmembrane precursor protein (APP). APP is believed to be normally released from membranes by the action of a protease referred to as APP secretase. Amyloid deposits have also been shown to contain the enzyme acetylcholinesterase (AChE). In this study, a protease activity associated with AChE was found to possess APP secretase activity, stimulating the release of a soluble 100K form of APP from HeLa cells transfected with an APP cDNA. The AChE-associated protease was strongly and specifically inhibited by soluble APP (10 nM) isolated from human brain. The AChE-associated protease cleaved a synthetic beta A4 peptide at the predicted cleavage site. As AChE is decreased in AD, a deficiency of its associated protease might explain why APP is abnormally processed in AD.
A Molecular Comparison of T Lymphocyte Populations Infiltrating the Liver and Circulating in the Blood of Patients With Chronic Hepatitis B: Evidence for Antigen–Driven Selection of A Public Complementarity–Determining Region 3 (Cdr3) Motif (2001)

Despite a large number of T cells infiltrating the liver of patients with chronic hepatitis B, little is known about their complexity or specificity. To characterize the composition of these T cells involved with the pathogenesis of chronic hepatitis B (CHB), we have studied the clonality of VbetaT cell receptor (TCR)-bearing populations in liver tissue by size spectratyping the complementarity-determining region (CDR3) lengths of TCR transcripts. We have also compared the CDR3 profiles of the lymphocytes infiltrating the liver with those circulating in the blood to see whether identical clonotypes may be detected that would indicate a virus-induced expansion in both compartments. Our studies show that in most of the patients examined, the T cell composition of liver infiltrating lymphocytes is highly restricted, with evidence of clonotypic expansions in 4 to 9 TCR Vbeta subfamilies. In contrast, the blood compartment contains an average of 1 to 3 expansions. This pattern is seen irrespective of the patient's viral load or degree of liver pathology. Although the TCR repertoire profiles between the 2 compartments are generally distinct, there is evidence of some T cell subsets being equally distributed between the blood and the liver. Finally, we provide evidence for a putative public binding motif within the CDR3 region with the sequence G-X-S, which may be involved with hepatitis B virus recognition.
Characterization of Lunasin Isolated from Soybean (2003)

Lunasin is a novel and promising chemopreventive peptide from soybean. We have shown previously that lunasin suppresses transformation of mammalian cells caused by chemical carcinogens and inhibits skin carcinogenesis in mice when applied topically. Although the lunasin gene was cloned from soybean, all experiments carried out so far in our lab have used synthetic lunasin and therefore there is no detailed description of natural lunasin isolated from soybean. We report here the first characterization of soybean lunasin that includes definitive identification by mass peptide mapping, partial purification, and measurement of bioactivities of the various purified fractions and protein expression in the developing seed. The identity of lunasin in the seed extracts was established by Western blot analysis and mass spectrometric peptide mapping. All lunasin fractions partially purified by anion exchange and immunoaffinity column chromatography suppress colony formation induced by the ras-oncogene and inhibit core H3-histone acetylation. During seed development, lunasin peptide appears 5 weeks after flowering and persists in the mature seed. Western blot analysis of different soybean varieties and commercially available soy proteins shows the presence of the peptide in varying amounts. These results demonstrate the feasibility of producing large quantities of natural lunasin from soybean for animal and human studies.