gebhart/patrepeval huggingface dataset:
Controlling velocity-limited systems to reduce residual vibration (2003)

To avoid vibration of robot arms when they are moved very rapidly, a set of shaped force profiles have been developed to minimize the excitation energy at the system's first natural frequency during motion. The system is assumed to be velocity-limited. The force profiles are constructed from a versine (one-cosine) function and its harmonics, with coefficients chosen to minimize the spectral magnitude near the system natural frequency. The profiles can be tuned to the closed-loop natural frequency of a closed-loop system with motor position and velocity feedback. When integrated twice, the force profile becomes a reference trajectory which serves to bring the system to peak velocity with minimum excitation at the first natural frequency. Using a suitable dwell time between acceleration and deceleration, a specified position can be reached quickly with minimum residual vibration and within while never exceeding the velocity limit.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Rationing and critical care medicine (2007)

As healthcare expenditures have continued to grow in the United States and elsewhere, the demand for cost-cutting measures has increased. This has led many to wonder if we are, in fact, rationing health care. Critical care is characterized by very high expenditures on a relatively few number of patients, many of whom do not survive, and it is therefore a likely place where rationing could occur. Although much has been written about the concept of rationing, there are few data about the practice, with the exception of studies that examined triaging in the intensive care unit. Research in this area is greatly hampered by the fact that identifying rationing can be very subjective given the relatively inconsistent methods by which critical care is actually practiced and the lack of a clear definition of rationing. This article reviews the concept of healthcare rationing by exploring the many different definitions and methods by which it could occur and the ethical principles underlying these methods. In addition, we review the pertinent literature on resource allocation and rationing in intensive care units.
Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle. (1992)

Two point mutations were identified within the gene encoding bovine CD18 in a Holstein calf afflicted with leukocyte adhesion deficiency (LAD). One mutation causes an aspartic acid to glycine substitution at amino acid 128 (D128G) in the highly conserved extracellular region of this adhesion glycoprotein, a region where several mutations have been found to cause human LAD. The other mutation is silent. Twenty calves with clinical symptoms of LAD were tested, and all were homozygous for the D128G allele. In addition, two calves homozygous for the D128G allele were identified during widespread DNA testing, and both were subsequently found to exhibit symptoms of LAD. The carrier frequency for the D128G allele among Holstein cattle in the United States is approximately 15% among bulls and 6% among cows. This mutation is also prevalent among Holstein cattle throughout the world, placing this disorder among the most common genetic diseases known in animal agriculture. All cattle with the mutant allele are related to one bull, who through the use of artificial insemination sired many calves in the 1950s and 1960s. The organization of the dairy industry and the diagnostic test described herein will enable nearly complete eradication of bovine LAD within 1 year. These results also demonstrate that bovine LAD is genetically homologous and phenotypically similar to human LAD, thus providing a useful animal model for studies of LAD and beta 2 integrin function.
Identification of the cellular targets of bioactive small organic molecules using affinity reagents (2008)

The elucidation of molecular targets of bioactive small organic molecules remains a significant challenge in modern biomedical research and drug discovery. This tutorial review summarizes strategies for the derivatization of bioactive small molecules and their use as affinity probes to identify cellular binding partners. Special emphasis is placed on logistical concerns as well as common problems encountered during such target identification experiments. The roadmap provided is a guide through the process of affinity probe selection, target identification, and downstream target validation.
Adoptive Transfer of Chimeric Fc ε RI Receptor Gene-Modified Human T Cells for Cancer Immunotherapy (2006)

Immunotherapeutic approaches involving genetic modification of T cells show promise in generating highly specific tumor-reactive effector cells for cancer treatment. Given the high affinity of Fc ε RI (the subtype I Fc receptor for IgE) for IgE monoclonal antibody (mAb), modification of T cells with chimeric Fc ε RI in combination with tumor-specific IgE mAbs is potentially a powerful and effective strategy to specifically target T cells to tumor cells. In this study, we retrovirally transduce human primary T cells with a cDNA encoding the extracellular domain of Fc ε RI linked to the hinge and transmembrane domains of Fc γ RI and the cytoplasmic domains of CD28 and T cell receptor ζ chain (Fc ε RI-CD28-ζ). We demonstrate that human T cells expressing Fc ε RI-CD28-ζ, in the presence of tumor-specific IgE mAb recognizing mouse CD8 antigen (Ly- 2.1+), can specifically secrete cytokine, proliferate, and mediate cytotoxic function after antigen ligation. Furthermore, adoptive transfer of Fc ε RI-CD28-ζ cells incubated with anti-Ly-2.1 IgE mAb significantly enhances the survival of irradiated nonobese diabetic-severe combined immunodeficiency mice bearing Ly-2.1+ tumor compared with control mice. Thus, this set of experiments demonstrates that Fc ε gene-engineered human T cells mediate effector function in vitro and in vivo in an IgE-dependent manner and thus a novel and valid approach for cancer therapy can now be further developed.
The effect of leaf water potential on the carbon-dioxide uptake rate during different growth stages of wheat (Triticum aestivum L.) (1990)

The effect of water stress on the CO2 uptake rate was measured at three different growth stages of wheat grown in Mitscherlich pots in a glasshouse experiment. Stress was induced by withholding water until the leaf water potential reached −2 000 kPa and −3 000 kPa, while control plants were irrigated continuously. Although stress inhibited the CO2 uptake rate of the entire plant, low stress levels briefly stimulated this process during the differentiation of the spikelet. Recovery of the CO2 uptake rate deteriorated with increased stress and at later growth stages, and no recovery was evident on alleviating severe stress during seed-filling. The CO2 uptake rate per unit living leaf area generally decreased under stress, while the recovery after severe stress was considerably lower than after moderate stress. During seed-filling there was no recovery whatsoever of the CO2 uptake rate per unit leaf area after the alleviation of severe stress.
Efficacy and Safety of Troglitazone in the Treatment of Lipodystrophy Syndromes (2000)

Troglitazone therapy improved metabolic control and increased body fat in patients with lipoatrophic diabetes. The substantial benefits of troglitazone must be balanced against the risk for hepatotoxicity, which can occur relatively late in the treatment course.
Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Pigs (2008)

Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.
Establishment and Characterization of Nine New Head and Neck Cancer Cell Lines (1997)

We established new cell lines from head and neck cancer patients for studies of adhesion molecules and cellular behavior in nine patients with primary or metastatic cancer treated at the Asan Medical Center. Explant cultures of fresh tumor tissue were used to develop new permanent tumor cell lines. Lines were tested for tumor formation and histology in nude mice. Flow cytometry and indirect immunofluorescence were used to assess DNA content and expression of the alpha 6, beta 4, and beta 1 integrin subunits and the intercellular adhesion molecule 1 (ICAM-1). In vitro growth patterns and adhesion to plastic were assessed using phase contrast microscopy. AMC-HN-1 to -8 were derived from patients with squamous cell carcinoma. AMC-HN-9 was from an undifferentiated carcinoma of the parotid gland. The 8 lines we tested produced nude mouse tumors that are identical to the histology of the original tumors. AMC-HN-1, -2, -5, and -9 have epithelioid or spindle cell morphology with poor cell-to-cell and cell-to-substrate adhesiveness. AMC-HN-3, -4, -7, and -8 grow as adherent epithelioid monolayers. AMC-HN-6 exhibits multilayer stratification. Four lines are near diploid, 4 are hyperdiploid and 1 is hypodiploid. Only three express ICAM-1. All lines express the alpha 6, beta 4, and beta 1 integrin subunits but to different extent. Four, AMC-HN-1, -2, -5, and -6, express the beta 4 integrin at low levels, AMC-HN-3, -4, -7, and -9, have intermediate beta 4 expression, and AMC-HN-8 has extremely high beta 4 expression. The AMC-HN cell lines are representative in vitro models for the study of head and neck cancer biology. Our preliminary results indicate a close relationship between integrin expression and cell adhesion in vitro.
The characterization of murine BCMA gene defines it as a new member of the tumor necrosis factor receptor superfamily (1998)

The BCMA gene is a new gene discovered by the molecular analysis of a t(4;16) translocation, characteristic of a human T cell lymphoma. It has no significant similarity with any known protein or motif, so that its function was unknown. This report describes the cloning of murine BCMA cDNA and its genomic counterpart. The mouse gene is organized into three exons, like the human gene, and lies in murine chromosome 16, in the 16B3 band, the counterpart of the human chromosome 16p13 band, where the human gene lies. Murine BCMA cDNA encodes a 185 amino acids protein (184 residues for the human), has a potential central transmembrane segment like the human protein and is 62% identical to it. The murine BCMA mRNA is found mainly in lymphoid tissues, as is human BCMA mRNA. Alignment of the murine and human BCMA protein sequences revealed a conserved motif of six cysteines in the N-terminal part, which strongly suggests that the BCMA protein belongs to the tumor necrosis factor receptor (TNFR) superfamily. Human BCMA is the first member of the TNFR family to be implicated in a chromosomal translocation.
The effect of chemical modification of amino acid side‐chains on collagen degradation by enzymes (2006)

In this study, the effects of specific chemical modifications of amino acid side-chains on the in vitro enzyme degradation of type I collagen was studied. Two monofunctional epoxides of different size and chemistry were used to modify lysine and methylglyoxal was used to modify arginine. Lysine residues were modified using glycidol, a small hydrophilic reagent or n-butylglycidylether, a larger hydrophobic reagent. Amino acid analysis, swelling measurements, in vitro enzyme degradation analyses (using either collagenase, trypsin, acetyltrypsin, or cathepsin B), and gel chromatography were used to determine the effects of each chemical modification on purified type I collagen. Collagen solubilization by enzymes depended upon the size and chemistry of epoxides used to modify lysine residues. Modification of lysine residues by glycidol and arginine modification by methylglyoxal together significantly reduced collagen solubilization by acetyltrypsin and collagenase, whereas increased collagen solubilization was observed for all enzymes after lysine modification with n-butylglycidylether combined with arginine modification by methylglyoxal. Gel chromatographic analyses of collagen fragments solubilized by acetyltrypsin from type I collagen revealed that both the extent of solubilization and sites of cleavage were altered after lysine and arginine modification. In contrast, lysine and arginine modification only altered the amount of collagen solubilized by collagenase and had no effect on the amount collagen solubilized by cathepsin B. The ability to modulate the enzyme degradation of collagen-based materials as demonstrated in this study may facilitate the design of novel scaffolds for tissue regeneration or collagen-based drug/protein/gene delivery systems.
Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies. (1995)

The Huntington disease (HD) phenotype is associated with expansion of a trinucleotide repeat in the IT15 gene, which is predicted to encode a 348-kDa protein named huntington. We used polyclonal and monoclonal anti-fusion protein antibodies to identify native huntingtin in rat, monkey, and human. Western blots revealed a protein with the expected molecular weight which is present in the soluble fraction of rat and monkey brain tissues and lymphoblastoid cells from control cases. In lymphoblastoid cell lines from juvenile-onset heterozygote HD cases, both normal and mutant huntingtin are expressed, and increasing repeat expansion leads to lower levels of the mutant protein. Immunocytochemistry indicates that huntingtin is located in neurons throughout the brain, with the highest levels evident in larger neurons. In the human striatum, huntingtin is enriched in a patch-like distribution, potentially corresponding to the first areas affected in HD. Subcellular localization of huntingtin is consistent with a cytosolic protein primarily found in somatodendritic regions. Huntingtin appears to particularly associate with microtubules, although some is also associated with synaptic vesicles. On the basis of the localization of huntingtin in association with microtubules, we speculate that the mutation impairs the cytoskeletal anchoring or transport of mitochondria, vesicles, or other organelles or molecules.
O‐Mannosylation of recombinant human insulin‐like growth factor I (IGF‐I) produced in Saccharomyces cerevisiae (1989)

A glycosylated form of recombinant human insulin-like growth factor I (IGF-I) expressed in Saccharomyces cerevisiae was shown to contain mannose as the only carbohydrate constituent. All oligosaccharide chains of the glycoprotein could be released by mild alkaline treatment, and separated from the protein by gel-permeation chromatography on Bio-Gel P-2. The structures of these O-linked carbohydrate chains were determined by 500-MHz 1H-NMR spectroscopy, affording the disaccharide Man alpha 1-2Man as the major component and the tetrasaccharide Man alpha 1-3Man alpha 1-2Man alpha 1-2Man as a minor component. Reference oligosaccharides were prepared from mannoproteins released from the cell wall of S. cerevisiae X2180 (alpha-wild type). In addition to previously reported structures, ranging from mannose to mannotetraose, the pentasaccharide Man alpha 1-3Man alpha 1-3Man alpha 1-2Man alpha 1-2Man was identified in the cell wall mannoprotein.
Enhanced Levels of Soluble and Membrane-Bound CD40 Ligand in Patients With Unstable Angina (1999)

This first demonstration of enhanced levels of soluble and membrane-bound forms of CD40L in angina patients, with particularly high levels in patients with unstable angina, suggests that CD40L-CD40 interaction may play a pathogenic role in both the long-term atherosclerotic process and in the triggering and propagation of acute coronary syndromes.
Single transistor oscillator based on a Graphene-Aluminum Nitride nano plate resonator (2013)

This paper reports on the first demonstration of a high frequency (245 MHz) single transistor oscillator based on Graphene-Aluminum Nitride (G-AlN) nano-plate resonator (NPR). For the first time, a 2-dimensional (2D) electrically conductive graphene layer was integrated on top of an ultra-thin (500 nm) AlN nano-plate and excited into a high frequency contour-extensional mode of vibration by piezoelectric transduction. The resulting ultra-thin, low mass and high frequency G-AlN nanomechanical resonator showed high values of electromechanical coupling coefficient (k <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ≈1.8%) and quality factor (Q <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> ≈1000) which enabled the implementation of a low phase noise (-87 dBc/Hz @ 1kHz offset and -125 dBc/Hz floor) single transistor oscillator. The experimental results also demonstrate the great potential of the proposed technology for the implementation of a new class of ultra-sensitive and low noise G-AlN resonant sensors.
Analysis of the Substrate Specificity of the Staphylococcus aureus Sortase Transpeptidase SrtA (2004)

The Staphylococcus aureus sortase transpeptidase SrtA isoform is responsible for the covalent attachment of virulence and colonization-associated proteins to the bacterial peptidoglycan. SrtA utilizes two substrates, undecaprenol-pyrophosphoryl-MurNAc(GlcNAc)-Ala-D-isoGlu-Lys(epsilon-Gly(5))-D-Ala-D-Ala (branched Lipid II) and secreted proteins containing a highly conserved C-terminal LPXTG sequence. SrtA simultaneously cleaves the Thr-Gly bond of the LPXTG-containing protein and forms a new amide bond with the nucleophilic amino group of the Gly(5) portion of branched Lipid II, anchoring the protein to this key intermediate that is subsequently polymerized into peptidoglycan. Here we describe the development of a general in vitro method for elucidating the substrate specificity of sortase enzymes. In addition, using immunofluorescence, cell adhesion assays, and transmission electron microscopy, we establish links between in vitro substrate specificity and in vivo function of the S. aureus sortase isoforms. Results from these studies provide strong supporting evidence of a primary role of the SrtA isoform in S. aureus adhesion and host colonization, illustrate a lack of specificity cross talk between SrtA and SrtB isoforms, and highlight the potential of SrtA as a target for the development of antivirulence chemotherapeutics against Gram-positive bacterial pathogens.
2'-Substituted chalcone derivatives as inhibitors of interleukin-1 biosynthesis (1993)

A series of 2'-substituted chalcone derivatives has been found to show potent inhibition of the production of IL-1 beta from human peripheral blood monocytes stimulated with lipopolysaccharide (LPS), with IC50 values in the 0.2-5.0-microM range. Some members of the series have also shown inhibition of septic shock induced in mice by injection of LPS, although with low potency. Qualitative structure-activity relationships have shown that the enone is required for activity, which may be mediated by conjugate addition of a biological nucleophile to the chalcone. Electron-poor aromatic rings beta to the ketone give enhanced potency. Although electronic effects in the other ring (directly attached to the ketone) are minimal, this ring must possess an ortho substituent for good activity without cytotoxicity, suggesting a degree of selectivity which would not be expected for simple, nonspecific alkylating agents.
Broadband intelligent networking: evolution of service control (2002)

Intelligent networking will be required in broadband to isolate complex service control from high performance switching. Architectures for narrowband intelligent networking are not directly applicable to broadband. Issues affecting the design of broadband intelligent networks are enhanced terminal intelligence, mobility, service complexity, private and public networking, and changing regulatory environments. Several different service controller types are presented and compared. A user/network interfaced switch controller is suggested. Broadband services and signalling issues and probable server/network evolution scenarios are discussed.
Infection of Human Dendritic Cells by a Sindbis Virus Replicon Vector Is Determined by a Single Amino Acid Substitution in the E2 Glycoprotein (2000)

The ability to target antigen-presenting cells with vectors encoding desired antigens holds the promise of potent prophylactic and therapeutic vaccines for infectious diseases and cancer. Toward this goal, we derived variants of the prototype alphavirus, Sindbis virus (SIN), with differential abilities to infect human dendritic cells. Cloning and sequencing of the SIN variant genomes revealed that the genetic determinant for human dendritic cell (DC) tropism mapped to a single amino acid substitution at residue 160 of the envelope glycoprotein E2. Packaging of SIN replicon vectors with the E2 glycoprotein from a DC-tropic variant conferred a similar ability to efficiently infect immature human DC, whereupon those DC were observed to undergo rapid activation and maturation. The SIN replicon particles infected skin-resident mouse DC in vivo, which subsequently migrated to the draining lymph nodes and upregulated cell surface expression of major histocompatibility complex and costimulatory molecules. Furthermore, SIN replicon particles encoding human immunodeficiency virus type 1 p55(Gag) elicited robust Gag-specific T-cell responses in vitro and in vivo, demonstrating that infected DC maintained their ability to process and present replicon-encoded antigen. Interestingly, human and mouse DC were differentially infected by selected SIN variants, suggesting differences in receptor expression between human and murine DC. Taken together, these data illustrate the tremendous potential of using a directed approach in generating alphavirus vaccine vectors that target and activate antigen-presenting cells, resulting in robust antigen-specific immune responses.