gebhart/patrepeval huggingface dataset:
The resonant gate transistor (1967)

A device is described which permits high- <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</tex> frequency selection to be incorporated into silicon integrated circuits. It is essentially an electrostatically excited tuning fork employing field-effect transistor "readout." The device, which is called the resonant gate transistor (RGT), can be batch-fabricated in a manner consistent with silicon technology. Experimental RGT's with gold vibrating beams operating in the frequency range 1 kHz < f <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</inf> < 100 kHz are described. As an example of size, a 5-kHz device is about 0.1 mm long (0.040 inch). Experimental units possessing <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</tex> 's as high as 500 and overall input-output voltage gain approaching + 10 dB have been constructed. The mechanical and electrical operation of the RGT is analyzed. Expressions are derived for both the beam and the detector characteristic voltage, the device center frequency, as well as the device gain and gain-stability product. A batch-fabrication procedure for the RGT is demonstrated and theory and experiment corroborated. Both single- and multiple-pole pair band pass filters are fabricated and discussed. Temperature coefficients of frequency as low as 90- 150 ppm/°C for the finished batch-fabricated device were demonstrated.
Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis (1994)

We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue axl message is detected in normal human bone marrow but not significantly in normal blood leukocytes. Cell separation experiments showed that axl is expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with the normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid blast crisis). Treatment of K562 cells with the phorbol ester, 12-O- tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau significantly induced axl expression, supporting a role for this kinase in the intracellular signaling of myeloid cells through a variety of biochemical pathways. These results suggest that the axl kinase may be operative in normal and malignant myeloid biology.
Characterization of the murine high Km glucose transporter GLUT2 gene and its transcriptional regulation by glucose in a differentiated insulin-secreting cell line. (1994)

In pancreatic beta-cells, the high Km glucose transporter GLUT2 catalyzes the first step in glucose-induced insulin secretion by glucose uptake. Expression of the transporter has been reported to be modulated by glucose either at the protein or mRNA levels. In this study we used the differentiated insulinoma cell line INS-1 which expresses high levels of GLUT2 and show that the expression of GLUT2 is regulated by glucose at the transcriptional level. By run-on transcription assays we showed that glucose induced GLUT2 gene transcription 3-4-fold in INS-1 cells which was paralleled by a 1.7-2.3-fold increase in cytoplasmic GLUT2 mRNA levels. To determine whether glucose regulatory sequences were present in the promoter region of GLUT2, we cloned and characterized a 1.4-kilobase region of mouse genomic DNA located 5' of the translation initiation site. By RNase protection assays and primer extension, we determined that multiple transcription initiation sites were present at positions -55, -64, and -115 from the first coding ATG and which were identified in liver, intestine, kidney, and beta-cells mRNAs. Plasmids were constructed with the mouse promoter region linked to the reporter gene chloramphenicol acetyltransferase (CAT), and transiently and stably transfected in the INS-1 cells. Glucose induced a concentration-dependent increase in CAT activity which reached a maximum of 3.6-fold at 20 mM glucose. Similar CAT constructs made of the human GLUT2 promoter region and the CAT gene displayed the same glucose-dependent increase in transcriptional activity when transfected into INS-1 cells. Comparison of the mouse and human promoter regions revealed sequence identity restricted to a few stretches of sequences which suggests that the glucose responsive element(s) may be conserved in these common sequences.
Collagen scaffolds for tissue engineering (2007)

There are two major approaches to tissue engineering for regeneration of tissues and organs. One involves cell-free materials and/or factors and one involves delivering cells to contribute to the regeneraion process. Of the many scaffold materials being investigated, collagen type I, with selective removal of its telopeptides, has been shown to have many advantageous features for both of these approaches. Highly porous collagen lattice sponges have been used to support in vitro growth of many types of tissues. Use of bioreactors to control in vitro perfusion of medium and to apply hydrostatic fluid pressure has been shown to enhance histogenesis in collagen scaffolds. Collagen sponges have also been developed to contain differentiating-inducing materials like demineralized bone to stimulate differentiation of cartilage tissue both in vitro and in vivo.
Inhibitory Effect of Tumor Metastasis in Mice by Saponins, Ginsenoside-Rb2, 20(R)- and 20(S)-Ginsenoside-Rg3, of Red ginseng. (1995)

We examined the inhibitory effect of two saponin preparations from Red ginseng, 20(R)- and 20(S)-ginsenoside-Rg3, in comparison with that of ginsenoside-Rb2, on lung metastasis produced by two highly metastatic tumor cells, B16-BL6 melanoma and colon 26-M3.1 carcinoma, in syngeneic mice. In an in vitro analysis, both saponin preparations showed a significant inhibition of adhesion to fibronectin (FN) and laminin (LM) by B16-BL6 melanoma. Similarly, they significantly inhibited the invasion of B16-BL6 cells into the reconstituted basement membrane (Matrigel)/FN in a dose-dependent manner. In an experimental metastasis model using B16-BL6 melanoma, consecutive intravenous (i.v.) administrations of 100 micrograms/mouse of 20(R)- or 20(S)-ginsenoside-Rg3 1, 2, 3 and 4 d after tumor inoculation led to a significant decrease in lung metastasis. The inhibitory effect of i.v. administration of both ginseng saponins on the tumor metastasis of B16-BL6 melanoma was also recognized in a low dose of 10 micrograms/mouse. The oral administration (p.o.) of both saponins (100-1000 micrograms/mouse) induced a significant decrease in lung metastasis of B16-BL6 melanoma. Moreover, both ginseng saponins were effective in inhibiting of lung metastasis produced by colon 26-M3.1 carcinoma. When 20(R)- or 20(S)-ginsenoside-Rg3 was orally administered consecutively after tumor inoculation in a spontaneous metastasis model using B16-BL6 melanoma, both of them significantly inhibited lung metastasis. In the experiment involving neovasculization by tumor cells in vivo, both mice groups given each saponin preparation after tumor inoculation exhibited a significant decrease in the number of blood vessels oriented toward the tumor mass, with no repression of tumor size. These findings suggest that both ginseng saponins, 20(R)- and 20(S)-ginsenoside-Rg3, possess an ability to inhibit the lung metastasis of tumor cells, and the mechanism of their antimetastatic effect is related to inhibition of the adhesion and invasion of tumor cells, and also to anti-angiogenesis activity.
Dispersion in total cost of care for Medicare fee-for-service (FFS) patients with metastatic pancreatic cancer receiving FDA-approved/NCCN Category 1 regimens at 340B verus non-340B institutions. (2021)

e18843 Background: The Department of Health and Human Services (HHS) designed the 340B drug pricing program to allow institutions that service specialty populations to acquire drugs at lower prices. Objective: To analyze the dispersion in total cost of care (TCOC) for Medicare FFS patients (pts) with metastatic pancreatic cancer (m-PANC) treated at 340B or non-340B institutions, by NCCN Category 1 regimen. Methods: We identified pts with m-PANC using ICD-10 diagnosis codes in the 2016-18 Medicare Parts A/B/D 100% Research Identifiable Files. Study pts had 2+ claims with a pancreatic cancer diagnosis and Medicare FFS coverage for 6 months pre- and 3 months post-metastasis diagnosis. Study pts were treated with NCCN Category 1 regimens: 1L gemcitabine monotherapy (gem-mono), 1L gemcitabine/nab-paclitaxel (gem-nab), 1L FOLFIRINOX (FFX), and 2L liposomal irinotecan-based regimen (nal-IRI). Pts were attributed to 340B or non-340B institutions based on plurality of chemotherapy claims. TCOC reflects insurer-paid services per line of therapy (LOT) for 3 categories: chemotherapy/supportive drugs (chemo/Rx), inpatient care (IP), and other outpatient care (OP). We grouped pts by quartile (qrt) and evaluated drivers of TCOC and mean rates of admissions (admits/pt). Results: We identified 2,697 (340B) and 3,839 (non-340B) pts taking NCCN Category 1 regimens. Gem-mono represented 1% and 4% of all pts in 340B and non-340B institutions, respectively. Gem-nab accounted for 72% of pts in both cohorts. For gem-nab, FFX, and nal-IRI pts, median TCOC was similar in both cohorts, although mean TCOC by qrt was lower at 340B institutions than non-340B institutions, except for gem-nab in the 1 st qrt. The components of TCOC were similar between 340B and non-340B institutions in all qrts. In both cohorts, % IP costs increased between the 1 st and 4 th qrt (340B:15% to 23%, non-340B:14% to 25%). From the 1 st to the 4 th qrt, admits/pt increased in both cohorts. In the 340B cohort, nal-IRI pts had the lowest admits/pt while gem-nab pts had the highest in all qrts. In the non-340B cohort, nal-IRI pts had the lowest admits/pt except for in the 1 st qrt. Conclusions: Median TCOC was lower at 340B institutions than non-340B institutions for all regimens, and the range of TCOC dispersion was also smaller at 340B institutions. Across qrts, chemotherapy accounted for approximately half the TCOC; however, IP costs were proportionally higher in the 4 th qrt. Comparing regimens, despite 2L nal-IRI pts being more heavily pretreated, median costs in each cohort were similar to 1L gem-nab and 1L FFX, while admits/pt were generally lower than 1L gem-nab and 1L FFX across qrts and cohorts.
An Interactive Strategy for the Assembly of Complex, Branched Oligosaccharide Domains on a Solid Support: A Concise Synthesis of the Lewisb Domain in Bioconjugatable Form (1994)

Minimal use of protecting groups is required in the synthesis of the branched hexa-saccharide Lewisb 1. Thus, donor and acceptor glycosyl units were linked stereo-selectively to the polymer-bound glycal in such a way that an oligosaccharide recognition element is formed which can be bound to a carrier protein.
A Three-Stage Alcohol Clamp Procedure in Human Subjects (2002)

Background Multiple factors can influence blood alcohol levels (BALs) after oral ethanol intake. To minimize the variability in BALs, an alcohol “clamping” method in which alcohol is administered intravenously has been previously reported. We have modified this method and developed a multistage alcohol clamp procedure in humans. Methods Infusion of alcohol to achieve sequentially increasing steady-state BALs at 50, 100, and 150 mg/dl (e.g., an alcohol clamp procedure) was performed in five subjects. The method used intravenous infusion of 6% alcohol in saline and followed a protocol generated by a physiologically based pharmacokinetic model for alcohol infusion. Real-time measurement of BALs was used to base decisions for necessary adjustments in the infusion rates on a negative feedback principle to achieve and maintain the desired BALs. Additionally, in three of these subjects, breath alcohol levels were determined simultaneously with BAL measurements. Results A three-stage alcohol clamp procedure was used to achieve BALs of 50, 100, and 150 mg/dl. The intra-assay and interassay variations for measurement of BALs were 1.6 and 2.1%, respectively. The coefficients of variation for the 50, 100, and 150 mg/dl alcohol clamps were 9.8, 5.6, and 4.6%, respectively. The deviation from target BALs for the three clamps were less than 5%. Breath alcohol levels were lower than BALs across all time points, with the mean ratio between the two being 0.84. Correlation analysis showed a very strong correlation between the two alcohol measurement methods (r= 0.96;p < 0.001). Conclusions A three-stage alcohol clamp procedure (50, 100, and 150 mg/dl) has been developed by following a protocol generated with a physiologically based pharmacokinetic model for alcohol infusion in human subjects. This is a suitable procedure to examine the responses on cognitive measures and physiologic parameters under steady states of desired BALs.
Hot Topic: Endogenous Production of n-3 and n-6 Fatty Acids in Mammalian Cells (2005)

Polyunsaturated fatty acids (PUFA) are important components of mammalian diets, and the beneficial effects of n-3 PUFA on human development and cardiovascular health have been well documented. Caenorhabditis elegans is one of the few animals known to be able to produce linoleic (LA, 18:2n-6) and alpha-linolenic (ALA, 18:3n-3) essential fatty acids. These essential PUFA are generated by the action of desaturases that successively direct the conversion of monounsaturated fatty acids (MUFA) to PUFA. The cDNA coding sequences of the C. elegans Delta(12) and n-3 fatty acid desaturases were each placed under the control of separate constitutive eukaryotic promoters and simultaneously introduced into HC11 mouse mammary epithelial cells by adenoviral transduction. Phospholipids from transduced cells showed a significant decrease in the ratios of both MUFA:PUFA and n-6:n-3 fatty acids relative to control cultures. The fatty acid profile of transduced cellular phospholipids revealed significant decreases in MUFA and arachidonic acid (20:4n-6), and increases in LA, ALA, and eicosapentaenoic acid (20:5n-3). The fatty acid composition of triacylglycerols derived from transduced cells was similarly, but less dramatically, affected. These results demonstrate the functionality of C. elegans fatty acid desaturase enzymes in mammalian cells. Expression of these desaturases in livestock might act to counterbalance the saturating effect that rumen microbial biohydrogenation has on the fatty acid profile of ruminant products, and allow for the development of novel, land-based dietary sources of n-3 PUFA.
Cytokines and the chronic inflammation of rheumatic disease. I. The presence of interleukin-1 in synovial fluids. (1984)

Sera and synovial fluids from patients with a variety of rheumatic diseases were assayed for interleukin-2 (IL-2) activity in a system utilizing the proliferative response of cultured human phytohaemagglutinin (PHA) T cell blasts. The synovial fluids from 14 rheumatoid arthritis, eight ankylosing spondylitis, three psoriatic arthritis and 11 osteoarthritis patients, all showed IL-2 activity. The amounts of IL-2 present in the fluids from different diseases were compared and ranged from 4.2 to 140.0 units/ml.
Suppression of signal fluctuation induced by crosstalk light in a gain saturated laser diode amplifier (1996)

This letter demonstrates that a gain saturated laser diode amplifier, due to its input/output characteristic, has the effect of reducing signal fluctuation. Bit error rate measurement shows that receiver sensitivity degradation caused by crosstalk light is improved with the amplifier. It also shows that there is an optimum saturation condition at which the sensitivity is efficiently improved.
The antiinflammatory activity of IgG: the intravenous IgG paradox (2007)

How high doses of intravenous IgG (IVIG) suppress autoimmune diseases remains unresolved. We have recently shown that the antiinflammatory activity of IVIG can be attributed to a minor species of IgGs that is modified with terminal sialic acids on their Fc-linked glycans. Here we propose that these Fc-sialylated IgGs engage a unique receptor on macrophages that, in turn, leads to the upregulation of an inhibitory Fcgamma receptor (FcgammaR), thereby protecting against autoantibody-mediated pathology.
Vasoactive intestinal peptide 1‐12: A ligand for the CD4 (T4)/human immunodeficiency virus receptor (1987)

A five-amino-acid (TDNYT) sequence of vasoactive intestinal polypeptide (VIP) shares homology with the proposed attachment sequences of the human immunodeficiency virus (HIV). Synthetic peptides with these sequences have previously been shown to block viral envelope (gp120) binding and HIV infectivity and to serve as agonists of the CD4 (or T4) receptor. Utilizing an in vitro human monocyte chemotaxis bioassay we examined novel synthetic VIP and gp120 sequences and characterized their pharmacological activities on monocyte chemotaxis. CD4 receptor activity is primarily specified by N-terminal (VIP [1-12]) amino acids. The profound immunosuppression of AIDS is not easily explained solely by virus infection. Recently described immunological functions of VIP are similar to some of the immunological abnormalities shown by patients with AIDS. An overproduction of a VIP-like molecule from viral sources (e.g. gp120) could explain some of the immune system impairments which have been described in AIDS.
Recent developments in DNA electrophoretic separations (1998)

DNA electrophoresis is now a fairly mature technology. Nevertheless, as we approach the 21st century, new ideas are frequently suggested that could lead to a revolution for DNA sequencing and mapping. Here, we review some of the novel concepts that have been studied since ca. 1990. Our review focuses on new separation mechanisms, new sieving matrices and recent conceptual advances.
Synthesis of Enantiomerically Pure (−)-(S)-Brevicolline (1999)

(-)-(S)-Brevicolline (1) and related beta-carbolines were synthesized using an enantiomerically pure Michael-acceptor synthon (3). Subsequent Pictet-Spengler reaction afforded the tetrahydro-beta-carboline skeleton, which, in turn, was transformed to the beta-carboline by catalytic dehydrogenation.
Structural basis for binding of human IgG1 to its high-affinity human receptor FcγRI (2015)

Cell-surface Fcγ receptors mediate innate and adaptive immune responses. Human Fcγ receptor I (hFcγRI) binds IgGs with high affinity and is the only Fcγ receptor that can effectively capture monomeric IgGs. However, the molecular basis of hFcγRI's interaction with Fc has not been determined, limiting our understanding of this major immune receptor. Here we report the crystal structure of a complex between hFcγRI and human Fc, at 1.80 Å resolution, revealing an unique hydrophobic pocket at the surface of hFcγRI perfectly suited for residue Leu235 of Fc, which explains the high affinity of this complex. Structural, kinetic and thermodynamic data demonstrate that the binding mechanism is governed by a combination of non-covalent interactions, bridging water molecules and the dynamic features of Fc. In addition, the hinge region of hFcγRI-bound Fc adopts a straight conformation, potentially orienting the Fab moiety. These findings will stimulate the development of novel therapeutic strategies involving hFcγRI.
Suppression of acute lymphoblastic leukemia by the human wild-type p53 gene. (1992)

Independent mutations in both alleles of the p53 tumor suppressor gene are a frequent finding in human T-cell acute lymphoblastic leukemia (T-ALL) cell lines and in the cells of some T-ALL patients in relapse. One major goal of studying the status of p53 (and other tumor suppressor genes) in human cancer is to facilitate the suppression of the tumorigenic phenotype through the restoration of the expression of the wild-type allele. While the efficient insertion of a suppressor into all cells of solid/metastatic human tumors may at present be impossible, insertion into leukemia cells may be feasible due to the accessibility of the leukemia cells in the body. To examine the feasibility of suppressing the tumorigenicity of human T-leukemia cells, the human T-ALL cell line Be-13, which lacks endogenous p53 protein, was infected with a recombinant retrovirus encoding the wild-type allele of human p53 (hwtp53). Expression of p53 reduced the growth rate of infected Be-13 cells in vitro, suppressed colony formation in methylcellulose cultures, and abrogated their tumorigenic phenotype in nude mice in vivo. These results suggest that suppression of the leukemic phenotype of relapse T-ALL-derived Be-13 cells is feasible. Acute leukemia cell suppression via high-efficiency infection with retroviruses encoding wtp53 may be feasible and beneficial in T-ALL cases as part of a bone marrow transplantation regimen in an effort to reduce the frequency of posttransplantation relapse.
Tiplaxtinin, a Novel, Orally Efficacious Inhibitor of Plasminogen Activator Inhibitor-1:  Design, Synthesis, and Preclinical Characterization (2004)

Indole oxoacetic acid derivatives were prepared and evaluated for in vitro binding to and inactivation of human plasminogen activator inhibitor-1 (PAI-1). SAR based on biochemical, physiological, and pharmacokinetic attributes led to identification of tiplaxtinin as the optimal selective PAI-1 inhibitor. Tiplaxtinin exhibited in vivo oral efficacy in two different models of acute arterial thrombosis. The remarkable preclinical safety and metabolic stability profiles of tiplaxtinin led to advancing the compound to clinical trials.
ADH1A variation predisposes to personality traits and substance dependence (2009)

Human personality traits are strong predictors or characteristics of many psychiatric disorders including substance dependence (SD). Recently, significant associations between alcohol dehydrogenase type 1A gene (ADH1A) and SD have been reported, which led us to investigate the impact of ADH1A variation on personality traits and risk of SD. Five hundred fifty-eight subjects with SD [398 European-Americans (EAs) and 160 African-Americans (AAs)], 517 college students (384 EAs and 133 European-origin Hispanics), and 448 healthy subjects (385 EAs, 48 AAs, and 15 European-origin Hispanics) participated. Personality traits were assessed in 247 subjects with SD (179 EAs and 68 AAs), all 517 college students, and 332 healthy subjects (285 EAs, 40 AAs, and 7 European-origin Hispanics). The relationships between ADH1A and personality traits were comprehensively examined using stepwise multivariate analysis of covariance (MANCOVA), and then decomposed by stepwise analysis of covariance (ANCOVA). The relationship between ADH1A and SD was examined using stepwise logistic regression analysis. Admixture effects on analyses were considered. Overall, Agreeableness and Conscientiousness were associated with the diplotypes, haplotypes, genotypes, and/or alleles of ADH1A in three of four phenotype groups including EA SD subjects, healthy subjects, and AA SD subjects (1.7 x 10(-4) <or= P <or= 0.055), but not college students. Neuroticism was associated with diplotype, haplotypes and genotypes in AA SD subjects (0.001 <or= P <or= 0.031). In addition, SD was associated with diplotypes, haplotypes, genotypes, and/or alleles of ADH1A (0.008 <or= P <or= 0.060). The present study demonstrates that the ADH1A variation may contribute to the genetic component of variation in personality traits and SD.