gebhart/patrepeval huggingface dataset:
Orthostatic stress and area under the curve of photoplethysmography waveform (2016)

Background. Recent studies have shown that shape and morphology of photoplethysmography (PPG) waveform can provide useful information about cardiovascular system. These parameters namely pulse amplitude, pulse width, pulse rise time and pulse reflected delay have been studied independently and there is information about the interaction of these parameters. There is no detailed description of calculating these parameters. We have described a detailed algorithm for calculating these parameters. We also investigated a new parameter calculated using area under the curve of PPG waveform (AUCPPG). All parameter were calculated using finger probe oximeter sensor from 22 subjects before and after orthostatic stress. Changes in AUCPPG were compared against pulse interval, amplitude, width, rise time of PPG pulse and pulse reflection delay (PRD). Results. We found that all parameters showed a decrease with orthostatic stress. PPG pulse width parameter was very inconsistent and changed significantly based on small change in shape of PPG waveform. AUCPPG showed strong correlation with pulse amplitude (r 0.85) in supine position, but that relationship decreased in upright position (r 0.64) as reflected peaks became more distinct and separated. Multivariable regression showed that PRD and rise had negative influence on AUCPPG. Male subjects showed higher AUCPPG values. Conclusion. We conclude that all PPG based parameters are effected by subject's position. Although AUCPPG is correlated with PAP width, it is an independent parameter that can be calculated more consistently than pulse width. From the results of our sample population we conclude AUCPPG is a better indicator of change in vascular tone than PAP amplitude or PAP width. Unlike other parameters AUCPPG incorporates the influence of both PAP and reflected waves.
Long-term regulated expression of growth hormone in mice after intramuscular gene transfer (1999)

Effective delivery of secreted proteins by gene therapy will require a vector that directs stable delivery of a transgene and a regulatory system that permits pharmacologic control over the level and kinetics of therapeutic protein expression. We previously described a regulatory system that enables transcription of a target gene to be controlled by rapamycin, an orally bioavailable drug. Here we demonstrate in vivo regulation of gene expression after intramuscular injection of two separate adenovirus or adeno-associated virus (AAV) vectors, one encoding an inducible human growth hormone (hGH) target gene, and the other a bipartite rapamycin-regulated transcription factor. Upon delivery of either vector system into immunodeficient mice, basal plasma hGH expression was undetectable and was induced to high levels after administration of rapamycin. The precise level and duration of hGH expression could be controlled by the rapamycin dosing regimen. Equivalent profiles of induction were observed after repeated administration of single doses of rapamycin over many months. AAV conferred stable expression of regulated hGH in both immunocompetent and immunodeficient mice, whereas adenovirus-directed hGH expression quickly extinguished in immunocompetent animals. These studies demonstrate that the rapamycin-based regulatory system, delivered intramuscularly by AAV, fulfills many of the conditions necessary for the safe and effective delivery of therapeutic proteins by gene therapy.
Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels (2003)

The purpose of the study was to examine endothelium-dependent and -independent vasodilation of conduit and resistance vessels in sickle cell anemia (HbSS). We measured the effects of intra-arterial infusion of methacholine, sodium nitroprusside, and NG-monomethyl-L-arginine (L-NMMA) on forearm blood flow using venous occlusion plethysmography in eight patients with HbSS and 11 HbAA controls. We assessed vasodilation of the conduit brachial artery using ultrasound in 17 patients with HbSS and 41 nonanemic controls. Forearm blood flow response to methacholine was similar in HbSS and HbAA, while the response to sodium nitroprusside was greater in those with HbSS. Nitric oxide synthase inhibition with L-NMMA attenuated methacholine-induced forearm blood flow to a lesser extent in HbSS compared to HbAA, suggesting diminished nitric oxide (NO) contribution to endothelium-dependent vasodilation. Flow-mediated and nitroglycerin-induced dilation were impaired in HbSS compared to controls and were not affected by the antioxidant vitamin C or the precursor substrate for NO synthesis L-arginine. NO bioactivity is reduced but differs in peripheral conduit and resistance vessels in HbSS. Resistance vessels have preserved response to exogenous NO donors but have diminished contribution of NO to endothelium-dependent vasodilation. Conduit vessels demonstrate impaired vasodilation to endogenous and exogenous NO.
Quasi-Cyclic Low Density Parity Check Codes (2003)

In this correspondence, the construction of low-density parity-check (LDPC) codes from circulant permutation matrices is investigated. It is shown that such codes cannot have a Tanner graph representation with girth larger than , and a relatively mild necessary and sufficient condition for the code to have a girth of or is derived. These results suggest that families of LDPC codes with such girth values are relatively easy to obtain and, consequently, additional parameters such as the minimum distance or the number of redundant check sums should be considered. To this end, a necessary condition for the codes investigated to reach their maximum possible minimum Hamming distance is proposed.
Multiplex Fluorescent In Situ Hybridization in Zebrafish Embryos Using Tyramide Signal Amplification (2005)

One of the strengths of the zebrafish is the ease with which in situ hybridization can be performed to determine spatial and temporal patterns of gene expression in whole embryos. Thus far, colorimetric detection methods are mainly used for these analyses. Here we describe a fluorescent in situ hybridization (FISH) protocol for whole-mount zebrafish embryos using tyramide signal amplification (TSA). An optimal set of reagents was identified that allows for simultaneous localization of gene expression patterns of two genes within the same embryo, permitting identification of colocalized expression within single cells. This protocol can be extended to perform multiplex studies by repetition of the TSA-based detection for each target sequentially with a different fluorescent dye label. To this effect, we demonstrate that this approach can be combined with standard horseradish peroxidase (HRP)-mediated immunocytochemistry procedures in addition to FISH.
Modeling the user in natural language systems (1988)

For intelligent interactive systems to communicate with humans in a natural manner, they must have knowledge about the system users. This paper explores the role of user modeling in such systems. It begins with a characterization of what a user model is and how it can be used. The types of information that a user model may be required to keep about a user are then identified and discussed. User models themselves can vary greatly depending on the requirements of the situation and the implementation, so several dimensions along which they can be classified are presented. Since acquiring the knowledge for a user model is a fundamental problem in user modeling, a section is devoted to this topic. Next, the benefits and costs of implementing a user modeling component for a system are weighed in light of several aspects of the interaction requirements that may be imposed by the system. Finally, the current state of research in user modeling is summarized, and future research topics that must be addressed in order to achieve powerful, general user modeling systems are assessed. 1
Flexible Piezoelectric ZnO–Paper Nanocomposite Strain Sensor (2010)

The fabrication of a mechanically flexible, piezoelectric nanocomposite material for strain sensing applications is reported. Nanocomposite material consisting of zinc oxide (ZnO) nanostructures embedded in a stable matrix of paper (cellulose fibers) is prepared by a solvothermal method. The applicability of this material as a strain sensor is demonstrated by studying its real-time current response under both static and dynamic mechanical loading. The material presented highlights a novel approach to introduce flexibility into strain sensors by embedding crystalline piezoelectric material in a flexible cellulose-based secondary matrix.
Age-related decrease in proteoglycan synthesis of human articular chondrocytes: The role of nonenzymatic glycation (1999)

In both aged and in vitro AGE-enriched cartilage, the rate of proteoglycan synthesis was negatively correlated with the degree of glycation. This suggests that the age-related increase in cartilage AGE levels may be responsible, at least in part, for the age-related decline in the synthetic capacity of cartilage.
Abstract 1781: HPN536, a T cell-engaging, mesothelin/CD3-specific TriTAC for the treatment of solid tumors (2018)

Abstract Mesothelin (MSLN) is a GPI-linked tumor antigen overexpressed in a variety of solid tumors, including ovarian, pancreatic, lung and triple-negative breast cancer. Normal tissue expression is restricted to single-cell, mesothelial layers lining the pleural, pericardial, and peritoneal cavities. Overexpression of MSLN is associated with poor prognosis in lung adenocarcinoma and triple-negative breast cancer. MSLN has been used as cancer target antigen for numerous modalities, including immunotoxins, vaccines, antibody drug conjugates and CAR-T cells. Early signs of clinical efficacy have validated MSLN as target, but therapies with improved efficacy are still needed to address the significant, unmet medical need posed by MSLN-expressing cancers. HPN536 is a ~50-kDa antibody derivative called TriTAC (Tri-specific T cell Activating Construct) designed to simultaneously bind to MSLN on tumor cells and to CD3ε on T cells with an affinity of 1 nM and 14 nM, respectively. Transient bispecific binding leads to the formation of an immunological cytolytic synapse, T cell activation and redirected tumor cell killing. A third domain of HPN536 binds non-covalently to serum albumin with an affinity of 8 nM to extend serum half-life life. Because TriTACs are built using single domain antibodies, TriTACs are much smaller than full size antibodies and are anticipated to demonstrate improved penetration of human tumors compared to full sized antibodies. HPN536 is produced by eukaryotic cell culture and secreted as a highly stable, single polypeptide. It binds with similar affinity to human and cynomolgus MSLN, albumin and CD3. When incubated in co-cultures with resting, human or cynomolgus T cells and human tumor cells, T cells are induced to release cytokines, to proliferate, and to specifically lyse MSLN-positive target cells with EC50 values at single-digit picomolar concentrations. In an exploratory toxicological study in non-human primates, HPN536 was well tolerated and showed pharmacokinetics in support of weekly dosing in humans. Preclinical characterization suggests that HPN536 is an efficacious and safe novel therapeutic candidate for the convenient treatment of patients with MSLN-expressing malignancies. Citation Format: Richard Austin, Wade Aaron, Patrick Baeuerle, Manasi Barath, Adrie Jones, Susan D. Jones, Che-Leung Law, Kathryn Kwant, Bryan Lemon, Anna Muchnik, Kenneth Sexton, Laurie Tatalick, Holger Wesche, Timothy Yu. HPN536, a T cell-engaging, mesothelin/CD3-specific TriTAC for the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1781.
Strain relaxation of compositionally graded InxGa1−xAs buffer layers for modulation-doped In0.3Ga0.7As/In0.29Al0.71As heterostructures (1992)

Modulation-doped In0.3Ga0.7As/In0.29Al0.71As heterostructures have been grown on GaAs substrates by molecular beam epitaxy using a compositionally step-graded InxGa1−xAs buffer layer. We found that the buffer layer produces essentially total relaxation with &amp;lt;2×106/cm2 dislocations present in the In0.3Ga0.7As layer. The structural perfection of this layer is reflected in the electrical and galvanomagnetic properties of its two-dimensional electron-gas channel which has a sheet-electron density of 1.2×1012/cm2, peak mobilities of 9 300 cm2/V s at room temperature and 31 000 cm2/V s at 77 K, and a mobility anisotropy of ∼4% along orthogonal 〈110〉 directions.
Induction of Apoptosis in Uninfected Lymphocytes by HIV-1 Tat Protein (1995)

Infection by human immunodeficiency virus-type 1 (HIV-1) is typified by the progressive depletion of CD4 T lymphocytes and deterioration of immune function in most patients. A central unresolved issue in acquired immunodeficiency syndrome (AIDS) pathogenesis is the mechanism underlying this T cell depletion. HIV-1 Tat protein was shown to induce cell death by apoptosis in a T cell line and in cultured peripheral blood mononuclear cells from uninfected donors. This Tat-induced apoptosis was inhibitable by growth factors and was associated with enhanced activation of cyclin-dependent kinases.
CaO‐Based CO2 Sorbents: From Fundamentals to the Development of New, Highly Effective Materials (2013)

The enormous anthropogenic emission of the greenhouse gas CO2 is most likely the main reason for climate change. Considering the continuing and indeed growing utilisation of fossil fuels for electricity generation and transportation purposes, development and implementation of processes that avoid the associated emissions of CO2 are urgently needed. CO2 capture and storage, commonly termed CCS, would be a possible mid-term solution to reduce the emissions of CO2 into the atmosphere. However, the costs associated with the currently available CO2 capture technology, that is, amine scrubbing, are prohibitively high, thus making the development of new CO2 sorbents a highly important research challenge. Indeed, CaO, readily obtained through the calcination of naturally occurring limestone, has been proposed as an alternative CO2 sorbent that could substantially reduce the costs of CO2 capture. However, one of the major drawbacks of using CaO derived from natural sources is its rapidly decreasing CO2 uptake capacity with repeated carbonation-calcination reactions. Here, we review the current understanding of fundamental aspects of the cyclic carbonation-calcination reactions of CaO such as its reversibility and kinetics. Subsequently, recent attempts to develop synthetic, CaO-based sorbents that possess high and cyclically stable CO2 uptakes are presented.
Valproate and Valproate-Analogues: Potent Tools to Fight Against Cancer (2002)

The branched-chain fatty acid valproic acid (VPA) is the most commonly used antiepileptic drug for treating generalized epilepsy. Although originally considered to be of low toxicity, VPA has proved to possess considerable teratogenic potential when applied to the pregnant epileptic women. During the last few years, it has become evident that some of the mechanisms which account for the malformations produced by VPA are related to distinct anti-tumor properties of this compound. This intriguing discovery opens novel aspects for the treatment of tumor patients. In the present review, the biological, biochemical and pharmacological properties of VPA are discussed. Analyses of structure-activity relationships can provide the necessary insight into the molecular structures responsible for the anti-tumor effects.
Splicing of a Novel Androgen Receptor Exon Generates a Constitutively Active Androgen Receptor that Mediates Prostate Cancer Therapy Resistance (2008)

The standard systemic treatment for prostate cancer (PCa) is androgen ablation, which causes tumor regression by inhibiting activity of the androgen receptor (AR). Invariably, PCa recurs with a fatal androgen-refractory phenotype. Importantly, the growth of androgen-refractory PCa remains dependent on the AR through various mechanisms of aberrant AR activation. Here, we studied the 22Rv1 PCa cell line, which was derived from a CWR22 xenograft that relapsed during androgen ablation. Three AR isoforms are expressed in 22Rv1 cells: a full-length version with duplicated exon 3 and two truncated versions lacking the COOH terminal domain (CTD). We found that CTD-truncated AR isoforms are encoded by mRNAs that have a novel exon 2b at their 3' end. Functionally, these AR isoforms are constitutively active and promote the expression of endogenous AR-dependent genes, as well as the proliferation of 22Rv1 cells in a ligand-independent manner. AR mRNAs containing exon 2b and their protein products are expressed in commonly studied PCa cell lines. Moreover, exon 2b-derived species are enriched in xenograft-based models of therapy-resistant PCa. Together, our data describe a simple and effective mechanism by which PCa cells can synthesize a constitutively active AR and thus circumvent androgen ablation.
A 2-1600-MHz CMOS clock recovery PLL with low-Vdd capability (1999)

A general-purpose phase-locked loop (PLL) with programmable bit rates is presented demonstrating that large frequency tuning range, large power supply range, and low jitter can be achieved simultaneously. The clock recovery architecture uses phase selection for automatic initial frequency capture. The large period jitter of conventional phase selection is eliminated through feedback phase selection. Digital control sequencing of the feedback enables accurate phase interpolation without the traditional need of analog circuitry. Circuit techniques enabling low Vdd operation of a PLL with differential delay stages are presented. Measurements show a PLL frequency range of 1-200 MHz at Vdd=1.2 V linearly increasing to 2-1600 MHz at Vdd=2.5 V, achieved in a standard process technology without low threshold voltage devices. Correct operation has been verified down to Vdd=0.9 V, but the lower limit of differential operation with improved supply-noise rejection is estimated to be 1.1 V.
Human Antibodies to Immunodominant C5 Region of HIV-1 gp120 Cross-React with HLA Class I on Activated Cells (1994)

Cross-reactive antibodies to HLA class I and HIV-1 gp120 were detected in the sera of HIV-1-positive individuals, and were found to share the same epitope specificity as a gp120-HLA class I cross-reactive monoclonal antibody (M38). The amino acid residues of HLA recognized by both M38 and the patient antibodies occur as a clustered pair in the HLA-C alpha 1 domain. These sequences (KYKR and RKLR) are shared by almost all HLA-C alleles and are available to antibody binding only on beta 2-microglobulin-dissociated HLA heavy chains expressed on activated cells. Similar to M38, the antibody-binding sites on HIV-1 gp120 were mapped to two noncontiguous stretches of amino acids (KYK and KAKR), which flank a hydrophobic area of the immunodominant C5 region involved in gp41 binding. Serum antibodies immunoaffinity purified on synthetic HLA and gp120 peptides representing the M38-reactive regions were shown to bind to both HLA and gp120 in Western blot, as well as to membrane-bound HLA heavy chains, and to exhibit selective complement-mediated lysis of activated T cells. No serum antibodies could be detected that bind to the gp120 C5 region (peptide IEPLGVAPT) flanked by the two HLA-like sequences.
Aminoglycoside accumulation kinetics in rat renal parenchyma (1983)

To test the hypotheses that the renal parenchymal accumulation kinetics of aminoglycosides can predict nephrotoxicity, we measured renal parenchymal concentrations in rats receiving gentamicin and tobramycin. In addition to comparing the drugs as single daily injections, we also examined the effect of multiple doses versus a single daily dose. Gentamicin accumulated to much greater concentrations in the kidney than did tobramycin. Gentamicin given twice daily accumulated more rapidly and to greater concentrations than did the same total dose given once daily. We conclude that aminoglycoside accumulation in the kidney depends on the drug and dose regimen. These differences may explain relative nephrotoxicities.
Isolation and Characterization of Acidothermus cellulolyticus gen. nov., sp. nov., a New Genus of Thermophilic, Acidophilic, Cellulolytic Bacteria (1986)

Twelve isolates of thermophilic, acidophilic, cellulolytic bacteria were obtained from three different primary enrichment cultures from acidic hot springs at Yellowstone National Park, Wyo. The three isolates which had the highest cellulolytic activity, as shown by the diameter of clearing zones surrounding colonies on cellulose agar plates, were selected for intensive study. All were gram-variable, nonsporulating aerobic rods which formed no pigment. They grew at 37 to 65°C, with optimum growth at 55°C. The pH range for growth was 3.5 to 7, with an optimum pH of 5. The guanine-plus-cytosine content of the deoxyribonucleic acid was 60.7 ± 0.6 mol%. The organisms are resistant to penicillin G at 100 μg/ml. They share several important features with Thermus strains, namely heterotrophic, aerobic, and thermophilic mode of growth; morphological features; sensitivity to lysozyme; and presence of catalase. They differ in other important aspects, such as the pattern of carbon sources utilized for growth, the pH and temperature profiles of growth, the pattern of sensitivity to antibiotics, the guanine-plus-cytosine content of DNA, the composition of amino acids in the cell walls, and the structure of the cell walls. Thermus species are very sensitive to penicillin G, whereas our strains are resistant. Our strains also are different, in important respects, from the genus Thermomicrobium. Therefore, we designate the organism Acidothermus cellulolyticus gen. nov., sp. nov., of which the type strain is our strain 11B, ATCC 43068.
Alternative splicing yields novel BMAL2 variants: tissue distribution and functional characterization (2002)

The BMAL2 gene encodes a member of the basic helix-loop-helix PER-ARNT-SIM family of transcription factors, which control diverse physiological processes including circadian rhythms. We identified four novel human BMAL2 transcripts that differ by alternative splicing within their NH2-terminal regions. Divergent expression of these and previously reported transcripts was observed among human tissues. The functional consequences of alternative splicing for transcriptional activation by CLOCK:BMAL2 heterodimers were assessed using luciferase reporter gene constructs that contained one of three diurnally regulated promoters, namely, those of the mouse period1, mouse vasopressin, and human plasminogen activator inhibitor-1 genes. These studies revealed that alternative splicing generates BMAL2 isoforms possessing high, medium, low, or no transcriptional activity. Similar results were obtained with each promoter, suggesting that alternative splicing may influence the amplitudes of both central and peripheral oscillators. Indeed, alternative splicing of BMAL2 may provide tissues with a rheostat capable of regulating CLOCK:BMAL2 heterodimer function across a broad continuum of potential transcriptional activities to accommodate varied metabolic demands and physiological roles.
Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males (1997)

These results support the concept that the immune response of females differs from males, and that females are immunologically better positioned to meet the challenge of sepsis.