gebhart/patrepeval huggingface dataset:
The T-cell receptor V beta gene usage in tumor-infiltrating lymphocytes and blood of patients with hepatocellular carcinoma. (1992)

To determine a possibly restricted T-cell receptor (TCR) repertoire in tumor-infiltrating lymphocytes (TIL) in response to tumor-associated antigens in patients with hepatocellular carcinoma (HCC), freshly isolated TIL (n = 5) and peripheral blood lymphocytes (PBL; n = 6; 3 paired with TIL) were studied for expression of TCR variable (V) beta regions. RNA purified from TIL or PBL was reverse-transcribed into complementary DNA. This complementary DNA was amplified by quantitative polymerase chain reaction with 22 primers specific for 20 TCR V beta gene families and a 3' constant (C) beta primer. As a reference for later quantitation, a fragment of TCR C alpha was coamplified with each V beta region. Using 32P-labeled 3' primers, the percentage of total V beta expression was calculated by measuring the cpm of each of the amplified products. In contrast to PBL of 6 control, healthy individuals, whose range of expression of each TCR V beta gene varied from 0 to 13%, the expression of some V beta genes in HCC TIL was as high as 33%, indicating a restricted TCR V beta usage in HCC TIL. When polymerase chain reaction-amplified complementary DNAs of the V beta 1 or V beta 3 genes obtained from two TIL preparations were cloned and sequenced, the same rearrangements were found in the majority of DNA clones. The particular V beta genes that were over- or underrepresented in TIL varied among the patients. In 3 of 6 PBL and 3 of 5 TIL, the V beta 3 gene was expressed with a relatively high frequency. The V beta 4 gene expression was consistently low in patients' TIL or PBL. In 3 paired PBL and TIL, V beta expression was similar. In 5 of 6 cases, HCC PBL had different TCR V beta frequencies from those seen in normal PBL. This analysis of TCR V beta usage in freshly isolated TIL and in PBL indicated that T-lymphocytes in patients with HCC might have restricted immunological reactivity and that V beta 3-restricted TIL might represent antitumor effector cells.
Asymmetric Cyclization via Memory of Chirality:  A Concise Access to Cyclic Amino Acids with a Quaternary Stereocenter (2003)

N-(omega-Bromoalkyl)-amino acid derivatives, readily prepared from natural alpha-amino acids, gave cyclic amino acids with a quaternary stereocenter by treatment with potassium hexamethyldisilazaide in DMF. The chirality of parent amino acids was almost completely preserved during an enolate-formation and cyclization process, giving aza-cyclic amino acids in up to 98% ee in retention of configuration. This method is applicable to the asymmetric synthesis of azetidine, pyrrolidine, piperidine, and azepane derivatives. The asymmetric cyclization seems to proceed via an axially chiral enolate intermediate and not through a concerted SEi process.
Study of smoke detection by analysis of saturation in video (2011)

This study provides a method to detect the smoke in a field by computer vision. The software of smoke extraction is developed by using the graphical programming language. In processing the video images, it utilizes the HSI model to extract statically and dynamically the pixels of the smoke with specific saturation. The other pixels that are filtered off are regarded as the backgrounds. Elimination of noises by morphological analysis in the filtered images is applied. The results are demonstrated to successfully extract the smokes in various videos, which shows that it is promising in future for our method to be integrated in the existing video security system or further in the on-site industrial safety equipment.
Alphabetic Data Entry via the Touch-Tone Pad: A Comment (1971)

Computer analysis indicates the feasibility of single-stroke keying for data entry of alphabetic names using the standard touch-tone telephone pad. In many practical job situations little ambiguity will result from the single-keying technique, and this ambiguity can be resolved under computer control.
Androgen receptor antagonists: a patent review (2008 – 2011) (2012)

Novel mechanisms provide a more informed basis for selecting a competitive antagonist; however, high potency and favorable in vivo properties remain paramount. Noncompetitive antagonists have theoretical advantages suggestive of improved clinical efficacy, but no clinical proof of concept as of yet.
Aberrant GAP-43 gene expression in Alzheimer's disease. (1995)

GAP-43 is a growth-associated phosphoprotein expressed at high levels in neurons during development, axonal regeneration, and neuritic sprouting. GAP-43 gene expression in mature neurons is probably functionally important for the structural remodeling of synapses as required for learning and establishing new memory. The widespread aberrant neuritic growth accompanied by impaired synaptic plasticity in Alzheimer's disease (AD) suggests that abnormal GAP-43 gene expression may contribute to the cascade of neurodegeneration. In the present study, end-stage AD brains exhibited reduced neuronal expression but increased glial cell levels of GAP-43 mRNA and protein. Glial cell localization of GAP-43 gene expression was confirmed by in situ hybridization of cerebral tissue, Northern blot analysis of microdissected cerebral white matter, and independent analysis of astrocytoma cell lines and primary malignant astrocytomas. In addition, in AD, GAP-43 immunoreactivity was translocated from the cytosol to membranes of swollen neuritic (dendritic) and glial cell processes throughout cerebral cortex and white matter. Downregulated and aberrant neuronal GAP-43 gene expression appears to reflect an important molecular lesion that precedes and progresses with the widespread synaptic disconnection and dementia in AD. At the same time, the presence of similar neuronal abnormalities in Pick's disease, diffuse Lewy body disease, Parkinson's disease, and Down syndrome suggests common mechanisms in the respective cascades of neurodegeneration. Finally, the finding of aberrantly increased glial cell GAP-43 gene expression in AD exposes a previously unrecognized neurodegenerative change that may account for the axonal loss and white matter atrophy detected early in the course of disease.
Interleukin-35-mediated induction of a novel regulatory T cell population (49.7) (2010)

Abstract Regulatory T cells (Tregs) play a critical role in the maintenance of immunological self tolerance and immune homeostasis. Due to their potent immunosuppressive properties, the ex vivo generation of regulatory T cells is an important goal of immunotherapy. We show that treatment of conventional T cells (Tconv) with the inhibitory cytokine IL-35 induces IL-35 expression and confers suppressive capacity, in the absence of Foxp3, IL-10 and TGFβ expression, upon Tconv cells. IL-35-dependent induced Tregs, termed iTR35, are strongly suppressive in vitro and in in vivo models including IBD, EAE, and a B16 tumor model. Treg-mediated suppression induces the generation of iTR35 in an IL-35- and IL-10-dependent manner in vitro and within the tumor microenvironment. Human IL-35 can mediate the generation of human iTR35 that express IL-35 and are suppressive. iTR35 may constitute a key mediator of infectious tolerance and ex vivo generated iTR35 may possess therapeutic utility in various human diseases.
Use of a Liter-Scale Microbial Desalination Cell As a Platform to Study Bioelectrochemical Desalination with Salt Solution or Artificial Seawater (2011)

Bioelectrochemical desalination is potentially advantageous because of bioenergy production and integrated wastewater treatment and desalination. In this work, the performance and energy benefits of a liter-scale upflow microbial desalination cell (UMDC) were evaluated. The UMDC desalinated both salt solution (NaCl) and artificial seawater, and the removal rate of total dissolved solid (TDS) increased with an increased hydraulic retention time, although TDS reduction in artificial seawater was lower than that in salt solution. Our analysis suggested that electricity generation was a predominant factor in removing TDS (more than 70%), and that other factors, like water osmosis and unknown processes, also contributed to TDS reduction. It was more favorable given the high energy efficiency, when treating salt solution, to operate the UMDC under the condition of high power output compared with that of high current generation because of the amount of energy production; while high current generation was more desired with seawater desalination because of lower salinity in the effluent. Under the condition of the high power output and the assumption of the UMDC as a predesalination in connection with a reversal osmosis (RO) system, the UMDC could produce electrical energy that might potentially account for 58.1% (salt solution) and 16.5% (artificial seawater) of the energy required by the downstream RO system. Our results demonstrated the great potential of bioelectrochemical desalination.
The current status of pulse oximetry (1986)

The history of the development of pulse oximetry is outlined and the principle of how the apparatus works is described. The instrument detects hypoxic hypoxia and the shape of the oxygen dissociation curve means that the minimum saturation alarm should be set at 94% in anaesthetic usage. It is accurate to within 2% and is usually unaffected by racial pigmentation, but accuracy can be affected in low perfusion states, hypothermia and in the presence of abnormal forms of haemoglobin and pigments in the blood. Its clinical evaluation in the operating theatre and intensive care unit is reported. It was found to be useful and reliable and would appear to have logistical and other advantages over current methods of detecting hypoxia. Pulse oximetry may make a significant contribution to the safety of anaesthetic practice.
Metabolic consequences of reduced gastric acidity (1985)

A review of the effect on metabolism of antacids, anticholinergics and histamine H2-antagonists is given. It is stated that long-term treatment with antacids by a variety of mechanisms can cause severe metabolic complications such as the milk-alkali syndrome and phosphorus depletion. The interaction with other drugs can also be marked. There is very little known of the effect of anticholinergics on metabolism. Clinical experience has not indicated that any serious consequences will occur. The authors have investigated the effect continuous treatment with cimetidine 400 mg at night or twice daily for three years on weight, haemoglobin, plasma iron, plasma folate, plasma vitamin B12, albumin and plasma calcium. The only significant difference that occurred was a slight decrease of plasma calcium within the reference values. In conclusion it is stated that there is very little indication that the moderate and inconstant reduction of acidity over 24 hours which can be achieved by anticholinergics or twice daily administration of presently available H2-antagonists will result in metabolic consequences arising from reduced acidity. Higher doses given more frequently might give a risk for bacterial overgrowth with metabolic consequences.
HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS (2006)

Regulatory T (Treg) cells accumulate in the lymphoid tissues of human immunodeficiency virus (HIV)-infected individuals, contributing to the inability of the immune system to control virus replication. We investigate here Treg-cell numbers and functional markers (FOXP3, CTLA-4, IDO, and TGF-beta1) in lymphoid tissues from untreated infected hosts with progressive or nonprogressive disease (HIV-infected humans and simian immunodeficiency virus [SIV]-infected macaques). We found that increased numbers of FOXP3(+) T cells as well as increased expression of Treg-cell-associated functional markers were detected only during progressive disease. Such increases were not correlated with immune activation. Of importance, a high-perforin/FOXP3 ratio was associated with nonprogressive disease, suggesting that the immune control of virus replication represents a balance between cell-mediated immune responses and Treg-cell-mediated counter regulation of such responses. Furthermore, using an in vitro model of Treg-cell-HIV interactions, we showed that exposure of Treg cells to HIV selectively promoted their survival via a CD4-gp120-dependent pathway, thus providing an underlying mechanism for the accumulation of Treg cells in infected hosts with active viral replication. Considered together, our findings imply that therapeutic manipulation of Treg-cell number and/or function could improve immune control of HIV infection.
Incidence of multiple sclerosis in the town of Sassari, Sardinia, 1965 to 1985 (1988)

Prevalence studies carried out in Sardinia from 1975 suggest an increasing occurrence of MS. However, it is questionable whether this increase represents a real change in MS incidence or simply reflects longer survival. Data from 79 patients indicated the average annual incidence for the period 1965 through 1985 was 3.4 per 100,000. On December 31, 1985, the prevalence rate was 69 per 100,000. Evaluation of MS temporal trends showed a significant increase in MS incidence during the study period: values ranged around two per 100,000 in the triennial periods 1965-1967, 1968-1970, and 1971-1973, and around five in each triennium from 1977 onward.
Oxidative refolding of IGF-1 yields two products of similar thermodynamic stability: A bifurcating protein-folding pathway (1993)

Can one protein sequence encode two structures? Oxidative folding of human insulin-like growth factor 1 (IGF-1), a globular protein of 70 residues, is shown to yield two products of similar thermodynamic stability. This observation is of particular interest in light of the recent demonstration that two of the three disulfide bonds in native IGF-1 rearrange in the presence of dithiothreitol [Hober, S., et al. (1992) Biochemistry 31, 1749-1756]. Kinetics of the IGF-1 folding pathway were monitored by high-performance liquid chromatography (rp-HPLC). Disulfide-pairing schemes of intermediates and products were established by peptide mapping. Two disulfide isomers were obtained as products: one with native insulin-like pairing [6-48; 18-61; 47-52] (designated native IGF-1; 60% yield) and the other with alternative pairing [6-47; 18-61; 48-52] (designated IGF-swap; 40% yield). The predominant early intermediate contains the single disulfide 18-61, which is shared in common by the two products. Relative yields of native IGF-1 and IGF-swap are independent of protein concentration under dilute conditions. In the absence of an added thiol reagent, each isomer is stable indefinitely at neutral pH; in the presence of an added thiol reagent, the two isomers interconvert with an Arrhenius activation barrier of 12 kcal/mol. Interconversion does not require complete reduction and yields the same ratio of products as initial folding, demonstrating thermodynamic control. Spectroscopic studies using circular dichroism (CD), infrared spectroscopy (FTIR), two-dimensional 1H-NMR (2D-NMR), and photochemical dynamic nuclear polarization (photo-CIDNP) suggest that IGF-1 and IGF-swap adopt similar secondary structures but distinct tertiary folds. Implications of these observations for understanding the topology of protein-folding pathways are discussed.
Population Pharmacokinetics of Ivosidenib (AG-120) in Patients with IDH1-Mutant Advanced Hematologic Malignancies (2018)

Abstract BACKGROUND: Ivosidenib, a potent mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor, is being assessed in a phase 1 study of mIDH1 advanced hematologic malignancies (NCT02074839). We characterized the pharmacokinetics (PK) of ivosidenib in this population, and the effects of patient/disease characteristics and concomitant medications. METHODS: Ivosidenib was given in continuous 28-day cycles at 100 mg twice daily and 300 mg, 500 mg, 800 mg, and 1200 mg once daily (QD). Enrollment is complete; 258 patients received ≥1 ivosidenib dose (78 in escalation, 180 in expansion); samples were available from 253 patients (223 received ivosidenib 500 mg QD). Ivosidenib concentrations were determined using validated liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based methods. Population PK modeling was conducted using NONMEM software. The impact of demographics, renal and hepatic function, disease type, Eastern Cooperative Oncology Group (ECOG) performance status, and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors/inducers and gastric acid reducers on ivosidenib PK was explored. RESULTS: Ivosidenib PK were best described using a 2-compartment model with first-order absorption, dose-dependent bioavailability, and a time-dependent change in relative bioavailability and clearance between Day 1 and steady state. Mean steady-state apparent clearance (CL/F) was 5.39 L/h (between-patient variability ~35%) and mean central volume of distribution (Vc/F) was 234 L (~47%). Less than dose-proportional bioavailability was observed, with a dose doubling translating to a ~40% increase in exposure. The moderate/strong CYP3A4 inhibitors voriconazole, fluconazole, and posaconazole were associated with 36%, 41%, and 35% reductions in CL/F, and hence 57%, 69%, and 53% increases in area under the plasma ivosidenib concentration-time curve (AUC), respectively (Figure 1). Baseline body weight had a significant impact on Vc/F. Low albumin at baseline and during treatment correlated with decreased CL/F and Vc/F. However, the effects of body weight and albumin did not appear to be clinically relevant. No effects of creatinine clearance or measures of liver function (alanine aminotransferase, aspartate aminotransferase, bilirubin, within the range studied) on ivosidenib CL/F were detected. Concomitant use of pantoprazole or famotidine did not affect ivosidenib CL/F. CONCLUSION: This population PK model of ivosidenib suggests that no dose adjustments are needed based on the range of patient and disease characteristics analyzed. Disclosures Le: Millennium: Patents &amp; Royalties; Agios: Employment, Equity Ownership. Wada:Certara: Employment; Agios: Consultancy. Dai:Agios: Employment, Equity Ownership. Fan:Agios: Employment, Equity Ownership. Liu:Agios: Employment, Equity Ownership. Liu:Agios: Employment, Equity Ownership. Attar:Agios: Employment, Equity Ownership. Agresta:Agios: Employment, Equity Ownership. Yang:Agios: Employment, Equity Ownership.
Promotional Effect of Sodium Barbiturate on Intestinal Tumors Induced in Rats by Dimethylhydrazine<xref ref-type="fn" rid="FN2">2</xref> (1979)

Noninbred Sprague-Dawley rats were administered 1,2-dimethylhydrazine hydrochloride (DMH) by gavage or methylazoxymethanol acetate by sc inoculation. Thereafter, one group was given water to which 0.1% sodium barbiturate was added, and the other was given drug-free water. They were examined 20 weeks after onset of the experiments. A direct relationship was noted between dosage of DMH and numbers of intestinal tumors induced in the rats. The rats provided with sodium barbiturate-supplemented water developed more intestinal tumors than did those that drank drug-free water.
P(SI‐MA)/2‐Nitrobenzyl Cholate: A Two‐Level, Solution‐Inhibition, Deep‐UV Resist System (1987)

Trimethylsilylmethyl methacrylate (SI) and methacrylic acid (MA) copolymerize with reactivity ratios of about one to give a material that has adequate aqueous‐base‐solubility and oxygen‐RIE resistance to serve as the top component of a bilevel resist system. A resin with a SI:MA ratio of 1.1:1 etches between and slower than hard‐baked HPR‐204, depending on the oxygen pressure in the reactor. Incorporation into P(SI:MA) of 20 w/o dinitrobenzyl cholate as a solution inhibitor results in a resist system that is capable of submicron resolution with a sensitivity of ∼0.2 J/cm2. Oxygen‐RIE pattern transfer into thick planarizing HPR‐204 is readily accomplished.
Acute Vulvovaginitis (2006)

A 24-year-old sexually active woman presents with a three-day history of vaginal pruritus and increased vaginal discharge. One year before presentation, she had the same symptoms, which resolved with use of an over-the-counter antifungal agent. She uses oral contraceptives for birth control. The physical examination reveals vulvar erythema and normal-appearing vaginal discharge. How should she be evaluated and treated?
Influence of maternal drug metabolism on the fetal toxicity induced by acetylsalicylic acid. (1982)

Investigations were performed to explore changes in fetal toxicity induced by acetylsalicylic acid (ASA) in pregnant animals treated by various means for maternal alterations. The fetotoxicity induced by ASA (500 mg/kg s.c.) was higher in rats than in mice. In mice with low enzyme activity, those displaying a longer sleeping time in pentobarbital-induced sleep, the ASA-fetotoxicity was higher than that of mice with shorter sleeping time. In rats pretreated with phenobarbital (0.05%), Zn (10 mg/l) and Cu (10 mg/l) in tap water and cysteine (200 mg/kg s.c.), fetal toxicity of ASA was reduced, whereas it was enhanced in rats pretreated with SKF-525A (200 mg/kg s.c.) and alpha-naphthyl acetic acid (200 mg/kg p.o.) and in nephrectomized rats. The UDPGT activity in hepatic 9000 x g supernate was higher in mice than in rats and the activity of mice was increased by phenobarbital and Cu. This study indicates that ASA-induced fetotoxicity can be positively modified by alterations in drug metabolizing activity.
Mammalian stanniocalcin-1 activates mitochondrial antioxidant pathways: new paradigms for regulation of macrophages and endothelium (2009)

The mammalian homolog of the fish calcium regulatory hormone stanniocalcin-1 (STC1) is ubiquitously expressed and likely functions in an autocrine/paracrine fashion. Mammalian STC1 does not appear to exert significant effects on serum calcium, and its physiological role remains to be determined. In macrophages, STC1 decreases intracellular calcium and cell mobility; attenuates the response to chemoattractants; and diminishes superoxide generation through induction of uncoupling protein-2 (UCP2). In cytokine-treated endothelial cells, STC1 attenuates superoxide generation and the activation of inflammatory pathways [c-Jun NH(2)-terminal kinase (JNK) and NF-kappaB]; maintains the expression of tight junction proteins, preserving the endothelial monolayer seal; and decreases transendothelial migration of leukocytes. Combined, the effects of STC1 on endothelial cells and macrophages predict potent anti-inflammatory action. Indeed, application of the anti-glomerular basement membrane (GBM) glomerulonephritis model to STC1 transgenic mice that display increased expression of STC1 transgene in endothelial cells and macrophages yields renal protection. Our data suggest that STC1 activates antioxidant pathways in endothelial cells and macrophages and displays cytoprotective and anti-inflammatory actions.
The use of a multiobjective evolutionary algorithm to increase flexibility in the search for better IMRT plans (2012)

Using an evolutionary algorithm as a tool, it was found that allowing more flexibility in the search space enhanced performance. The two strategies of (a) varying the weights and reference doses in the objective function and (b) removing the constraint of equal penalties for all voxels in a structure both generated sets of plans that dominated sets of plans considered to be "Pareto optimal" within the conventional, more limited search space. When considering voxel-specific objectives, the very large search space can lead to convergence problems in the MOEA for complex cases, but this is not an issue for the VSI algorithm.