gebhart/patrepeval huggingface dataset:
Animal Models for Heart Failure (2006)

Heart failure (HF) is a major cause of morbidity and mortality worldwide. Although many therapeutic means are available to prolong the life of HF patients, why HF develops is still poorly understood. Investigators still seek a truly appropriate animal model that will reliably mimic human HF, so that the cause of the disease can be targeted and proper therapeutic modalities implemented. HF is a complex condition in which multiple molecular mechanisms interact, resulting in compromised cardiac function and often death. Once this elusive animal model is found, investigators will be able to translate findings from the model to human disease, thereby allowing analysis of the molecular changes and dissecting out multiple complicated changes in HF cascade. In this chapter, we describe the methodology that is used to analyze both transcriptional and translational molecular changes and correlate them with cardiac function to assess the cause-and-effect relationship to HF. We used one particular animal model of HF as an example (induced by causing overexpression of myotrophin specifically in the heart) that allowed us to analyze the changes during initiation, progression, and transition of hypertrophy to HF. We have also summarized some other animal models of HF currently available to study mechanisms of HF.
Chromosome partitioning in Escherichia coli: novel mutants producing anucleate cells (1989)

To study the chromosomal partitioning mechanism in cell division, we have isolated a novel type of Escherichia coli mutants which formed anucleate cells, by using newly developed techniques. One of them, named mukA1, is not lethal and produces normal-sized anucleate cells at a frequency of 0.5 to 3% of total cells in exponentially growing populations but does not produce filamentous cells. Results suggest that the mutant is defective in the chromosome positioning at regular intracellular positions and fails frequently to partition the replicated daughter chromosomes into both daughter cells, resulting in production of one anucleate daughter cell and one with two chromosomes. The mukA1 mutation causes pleiotropic effects: slow growth, hypersensitivity to sodium dodecyl sulfate, and tolerance to colicin E1 protein, in addition to anucleate cell formation. Cloning of the mukA gene indicates that the mukA1 mutation is recessive and that the mukA gene is identical to the tolC gene coding for an outer membrane protein.
On the retention time distribution of dynamic random access memory (DRAM) (1998)

The retention time distribution of high-density dynamic random access memory (DRAM) has been investigated. The key issue for controlling the retention time distribution has been clarified and its model has been proposed for the first time. Trench capacitor cell with 0.6-/spl mu/m ground rule was evaluated. It was found that the retention time distribution consists of "tail distribution" and "main distribution." "tail distribution," by which DRAM refresh characteristics are restricted, depends on the boron concentration of the memory cell region. As boron concentration of the memory cell region increases, "tail distribution" is enhanced. This enhancement is due to the increase of the junction leakage current from the storage node. For the purpose of accounting for the nature of "Tail Distribution," the concept of thermionic field emission (TFE) current has been introduced. The high electric field at pn junction of the storage node enhances thermionic field emission from a deep level. The activation energy of the deep level is normally distributed among the memory cells, which leads to the normal distribution of log(retention time). Two methods for reducing "tail distribution" are proposed. One is to reduce the electric field of the depletion layer of the storage node. The other is to reduce the concentration of the deep level for TFE current.
ChemInform Abstract: STUDIES RELATED TO ANTITUMOR ANTIBIOTICS. PART VII. SYNTHESIS OF STREPTONIGRIN ANALOGS AND THEIR SINGLE STRAND SCISSION OF DNA (1976)

Abstract Die Synthese einer Gruppe von 2‐(o‐Nitrophenyl)‐ und 2‐(o‐Aminophenyl)‐5,8‐chinolindionen, die mit dem Antitumor‐Antibioticum Streptonigrin (I) verwandt sind, wird beschrieben: Behandlung des aus den Komponentenll) und (III) (modifizierte Skraup‐Synthese) erhältlichen Chinolins (IVa) mit HBr gibt das Hydrochinon (IVb), das 1. über das Dibromid (Va) in das Amino‐brom‐Derivat (Vb) und 2. über das Dichlorid (VIa) in das Methoxychlor‐Derivat (VIb) übergeführt wird.
Severe Psoriasis – Oral Therapy with a New Retinoid (1978)

Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Doses of 25 mg b.i.d., 25 mg t.i.d. and 50 mg b.i.d. were administered orally to 27 patients suffering from severe chronic generalized psoriasis. The clinical efficacy was evaluated by means of a new index, psoriasis area and severity index (PASI) based on severity and area of psoriatic lesions. At doses of 25 mg t.i.d. or 50 mg b.i.d. Ro 10--9359 proved to be an extremely potent antipsoriatic drug. A more than 90% reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4-8 weeks of treatment. This good effect lasted about 5 weeks after treatment. Side effects were frequent, but mostly mild and completely reversible after termination of treatment.
Dendritic cell-based cancer therapy. (2003)

Dendritic cell (DC)-based cancer immunotherapy has been shown to be safe and feasible. In clinical pilot studies, DCs primed with tumor antigens have successfully been used to induce tumor-specific immunity and obtain some clinical responses in cancer patients. Even though many advances have been achieved over the past years, we are still far from a unifying therapy concept. This review will discuss the current research driving the rapidly growing field of DC-based cancer immunotherapy and highlight some recent progress related to critical issues such as DC preparation, choice and loading of antigen, and the route of administration.
Improved approximation of the Brinkman equation using a lattice Boltzmann method (2001)

In this Brief Communication, a new approach to generalize the lattice Boltzmann method to produce fluid flow consistent with the Brinkman equation is presented. The method described in this communication both eliminates second order errors in velocity and improves stability over that of a previously proposed lattice Boltzmann-based model.
Development of inhibitors of protein farnesylation as potential chemotherapeutic agents (1995)

Protein prenylation, adding either the 15-carbon isoprenoid farnesyl or the 20-carbon isoprenoid geranylgeranyl to cysteine residue(s) at or near the C-termini of proteins, is a recently identified post-translational modification that localizes some proteins to a membrane compartment. One of the most intensely studied prenylated proteins is Ras, a low molecular weight GTP-binding protein that plays an important role in the regulation of cell proliferation. Proteins encoded by ras genes with oncogenic mutations are capable of transforming cells in culture. Such mutated ras genes are frequently found in a wide variety of human tumors. Localization of the Ras oncoprotein to the cytoplasmic face of the plasma membrane via farnesylation is essential for efficient cell transforming ability. Thus, inhibition of the Ras farnesylation reaction is a possible anti-cancer strategy. Several strategies have been employed to inhibit Ras farnesylation, including inhibition of isoprenoid biosynthesis and inhibition of the enzyme which catalyzes the farnesylation reaction, farnesyl-protein transferase (FPTase). Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate limiting enzyme in isoprenoid biosynthesis, inhibit Ras farnesylation and block the growth of ras-transformed cells. However, antiproliferative effects do not result from specific inhibition of Ras farnesylation; they are also observed in cells transformed by raf, which is independent of Ras farnesylation. A more specific approach to inhibiting Ras farnesylation is to inhibit FPTase. Using random screening of natural products and a rational design approach, a variety of compounds that specifically inhibit FPTase have been isolated.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical outcome measures for trials in Duchenne muscular dystrophy: report from International Working Group meetings (2011)

In June 2010, 25 representatives from Europe and the US met in Washington, DC, USA, to discuss clinical outcome measures in Duchenne muscular dystrophy (DMD) in the context of clinical trial design and analysis. The workshop was organized in response to a September 2009 European Medicines Agency meeting where a clear directive was given that an international consensus needs to be developed that provides a foundation for age-appropriate clinical outcome measures for use in clinical trials of emerging therapeutics for DMD. Data were presented from eight multicenter longitudinal datasets, representing nearly 1900 patients over a 20-year time period. This experience confirmed the feasibility of repeated evaluations performed at multiple sites and addressed several core issues in drug development for DMD, such as the 'new' natural history in the steroidera, reliability and sensitivity of specific outcome measures, as well as disease staging and patient selection. These data form a valuable asset for academic investigators, pharmaceutical sponsors and regulatory agencies involved in DMD therapeutics. The group remains committed working together on a number of collaborative goals to support the therapeutics development effort in this orphan disease and to make these data available to stakeholders working in the field.
The Extraordinary Active Site Substrate Specificity of pp60c−src (1995)

We report the first active site substrate specificity analysis of a tyrosine-specific protein kinase, namely pp60c-src. Like the cAMP-dependent protein kinase and protein kinase C, pp60c-src will phosphorylate an assortment of achiral residues attached to active site-directed peptides. Furthermore, pp60c-src phosphorylates both aromatic and aliphatic alcohols. However, the substrate specificity of pp60c-src is much broader than that of the two previously examined serine/threonine-specific protein kinases. We have previously shown that both the cAMP-dependent protein kinase and protein kinase C will utilize a wide array of non-amino acid residues as substrates, as long as the distance between the hydroxyl moiety and the adjacent peptide backbone is comparable with that present in serine and threonine (Kwon, Y.-G., Mendelow, M., and Lawrence, D. S. (1994) J. Biol. Chem. 269, 4839-4844). In marked contrast, pp60c-src does not discriminate against substrates on the basis of chain length, catalyzing the phosphorylation of residues that contain anywhere from 2-12 carbons between the alcohol functional group and the adjacent peptide bond. In addition, pp60c-src phosphorylates L-serine in an active site-directed peptide. The possible structural basis for the multiple specificity of pp60c-src is discussed. Finally, the active site specificity of pp60c-src is not just limited to L-amino acid residues, but also extends into the realm of D-amino acids as well.
The ubiquitin‐mediated proteolytic pathway and mechanisms of energy‐dependent intracellular protein degradation (1984)

In this review we briefly describe the lysosomal system, consider the evidence for multiplicity of protein degradation pathways in vivo, discuss in detail the ubiquitin-mediated pathway of intracellular ATP-dependent protein degradation, and also the possible significance of ubiquitin-histone conjugates in chromatin. For detailed discussions of the various characteristics and physiological roles of intracellular protein breakdown, the reader is referred to earlier reviews [1-7] and reports of recent symposia [8-10]. Information on the ubiquitin system prior to 1981 was described in an earlier review [11]. Hershko has briefly reviewed more recent information [12].
Endoscopic study of the gastro-intestinal tolerance of glucamethacin (1978)

A gastroscopic study was carried out in patients with rheumatic disorders to investigate the gastric tolerance of glucamethacin, a new, non-steroidal anti-inflammatory agent. The first stage was a double-blind crossover comparison of the effects of glucamethacin (420 mg/day) and indomethacin (100 mg/day), each given for 15 days in random order to 30 patients. In the second, open stage, 70 such patients, most of whom also had gastrointestinal pathology, received glucamethacin (420 mg/day) for 25 days. The results of endoscopic findings showed that significantly fewer (p less than 0.05) gastric lesions were produced after treatment with glucamethacin than after indomethacin. In the patients with gastro-duodenal pathology treated only with glucamethacin there was no change in endoscopy findings in 74% of the patients and only slight changes in the others.
B-type natriuretic peptide infusions in acute myocardial infarction (2007)

Nesiritide, given soon after MI, induced increments in plasma cGMP and CNP and decrements in other endogenous cardiac peptides with a neutral effect on renal function and a trend towards favourable ventricular remodelling.
Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters (2014)

By 2025, more than 500 M people worldwide will suffer from diabetes; 125 M will develop foot ulcer(s) and 20 M will undergo an amputation, creating a major health problem. Understanding how these wounds become chronic will provide insights to reverse chronicity. We hypothesized that oxidative stress (OS) in wounds is a critical component for generation of chronicity. We used the db/db mouse model of impaired healing and inhibited, at time of injury, two major antioxidant enzymes, catalase and glutathione peroxidase, creating high OS in the wounds. This was necessary and sufficient to trigger wounds to become chronic. The wounds initially contained a polymicrobial community that with time selected for specific biofilm-forming bacteria. To reverse chronicity we treated the wounds with the antioxidants α-tocopherol and N-acetylcysteine and found that OS was highly reduced, biofilms had increased sensitivity to antibiotics, and granulation tissue was formed with proper collagen deposition and remodeling. We show for the first time generation of chronic wounds in which biofilm develops spontaneously, illustrating importance of early and continued redox imbalance coupled with the presence of biofilm in development of wound chronicity. This model will help decipher additional mechanisms and potentially better diagnosis of chronicity and treatment of human chronic wounds.
Factors Governing the Expression of a Bacterial Gene in Mammalian Cells (1981)

Cultured monkey kidney cells transfected with simian virus 40 (SV40)-pBR322-derived deoxyribonucleic acid (DNA) vectors containing the Escherichia coli gene (Ecogpt, or gpt) coding for the enzyme xanthine-guanine phosphoribosyltransferase (XGPRT) synthesize the bacterial enzyme. This paper describes the structure of the messenger ribonucleic acids (mRNA's) formed during the expression of gpt and an unexpected feature of the nucleotide sequence in the gpt DNA segment. Analyses of the gpt-specific mRNA's produced during infection of CV1 cells indicate that in addition to the mRNA's expected on the basis of known simian virus 40 RNA splicing patterns, there is a novel SV40-gpt hybrid mRNA. The novel mRNA contains an SV40 leader segment spliced to RNA sequences transcribed from the bacterial DNA segment. The sequence of the 5'-proximal 345 nucleotides of the gpt DNA segment indicates that the only open translation phase begins with an AUG about 200 nucleotides from the end of the gpt DNA. Two additional AUGs as well as translation terminator codons in all three phases precede the XGPRT initiator codon. Deletion of the two that are upstream of the putative start codon increases the level of XGPRT production in transfected cells; deletion of sequences that contain the proposed XGPRT initiator AUG abolishes enzyme production. Based on the location of the XGPRT coding sequence in the recombinants and the structure of the mRNA's, we infer that the bacterial enzyme can be translated from an initiator AUG that is 400 to 800 nucleotides from the 5' terminus of the mRNA and preceded by two to six AUG triplets.
A comparison of molecular hyperpolarizabilities from gas and liquid phase measurements (1998)

The first and second hyperpolarizabilities (β and γ) of eight molecules at a fundamental wavelength of 1064 were measured by gas-phase electric-field-induced second-harmonic generation (EFISH), gas-phase hyper-Rayleigh scattering (HRS), and liquid-phase HRS experiments. The EFISH measurements give accurate values of β and γ for these molecules in the gas phase, and the HRS measurements show that the effective β of these molecules in the liquid is enhanced over the gas-phase value by a factor which varies from ≈0.4 to 2.0, over and above the Lorentz local field factors. Combining all of the measurements provides an accurate, absolute determination of the effective β for HRS in the liquid phase. The results for CCl4, suitable as reference standards, are 〈βVV2〉1/2=18.6±0.7 au in the liquid phase and βxyz=20.7±1.6 au in the gas phase. Comparison of measurements between hydrogenated and deuterated molecules indicates that vibrational contributions to β are small.
Sumatriptan ‐ Nonresponders: A Survey in 366 Migraine Patients (1996)

Sumatriptan, notably after subcutaneous administration, is highly effective in the acute treatment of migraine in the majority of patients. The response is consistent within patients and over time. To determine risk factors for nonresponse to sumatriptan, we compared clinical characteristics in responders and nonresponders and, within patients, between attacks with and without response. We found no differences at the strict level of significance (P < 0.001 because of multiple comparisons), but only tendencies for differences (0.001 < P < 0.05) in either the subcutaneous or oral groups. In the subcutaneous group, nonresponders had a higher body mass index, migraine onset at an earlier age, and, most importantly, they treated their migraine attacks earlier. In the oral group, nonresponders had attacks associated with more severe vomiting and photophobia, more often went to sleep or rest, and more frequently experienced initial worsening of the headache after sumatriptan administration. Within patients, no differences were found between attacks with and without response. In conclusion, we found few, if any, clinically relevant risk factors for nonresponse to sumatriptan. Administration of sumatriptan too early was the strongest indicator and should be avoided.
The Personal Presence System---hardware architecture (1994)

The Personal Presence System (PPS) experimental prototype is being designed to support multiparty multimedia visual services which use advanced video combining techniques. This paper is a companion to another paper in this proceedings: “The Personal Presence System—A Wide Area Network Service Resource for the Real Time Composition of Multipoint Multimedia Communications” which contains a detailed service description.
Improving retrieval performance by relevance feedback (1990)

Relevance feedback is an automatic process, introduced over 20 years ago, designed to produce improved query formulations following an initial retrieval operation. The principal relevance feedback methods described over the years are examined briefly, and evaluation data are included to demonstrate the effectiveness of the various methods. Prescriptions are given for conducting text retrieval operations iteratively using relevance feedback. © 1990 John Wiley & Sons, Inc.
[Duloxetine. A new preparation for patients with urinary incontinence]. (2005)

Stress Urinary Incontinence is a common symptom among women. The urethral closure is insufficient. Pelvic floor exercise can minish the symptoms, but many women need an operation. Duloxetine, a new drug, is believed to strengthen the contraction of the external urethral sphincter through central neuromodulation, resulting in enhanced urethral closure during the urine storage phase. In controlled studies a significant effect are found in women suffer from Stress Urinary Incontinence. Discontinuate rates for adverse events were high especially nausea and fatigue. The adverse event deminish after 4 weeks.
Emergence in Asia of Foot-and-Mouth Disease Viruses with Altered Host Range: Characterization of Alterations in the 3A Protein (2001)

In 1997, an epizootic in Taiwan, Province of China, was caused by a type O foot-and-mouth disease virus which infected pigs but not cattle. The virus had an altered 3A protein, which harbored a 10-amino-acid deletion and a series of substitutions. Here we show that this deletion is present in the earliest type O virus examined from the region (from 1970), whereas substitutions surrounding the deletion accumulated over the last 29 years. Analyses of the growth of these viruses in bovine cells suggest that changes in the genome in addition to the deletion, per se, are responsible for the porcinophilic properties of current Asian viruses in this lineage.
Vaccination of Seronegative Volunteers with a Human Immunodeficiency Virus Type 1env/revDNA Vaccine Induces Antigen‐Specific Proliferation and Lymphocyte Production of β‐Chemokines (2000)

There is a pressing need to test novel vaccine concepts in an effort to develop an effective vaccine for human immunodeficiency virus (HIV) type 1. A phase I clinical study was done to test the immunogenicity of an HIV env/rev DNA vaccine, which was administered intramuscularly to HIV-1-seronegative persons. Subjects received 3 doses of vaccine at a single concentration (100 or 300 microgram) at 0, 4, 8, and 24 weeks. In at least 1 of multiple assays, the 6 subjects who received the 300-microgram dose had DNA vaccine-induced antigen-specific lymphocyte proliferative responses and antigen-specific production of both interferon-gamma and beta-chemokine. Furthermore, 4 of 5 subjects in the 300 microgram-dose group responded to both the rev and env components of the vaccine. The responses did not persist within inoculated individuals and scored in different individuals at different times in the trial. This study supports that HIV-1 DNA vaccine antigens can stimulate multiple immune responses in vaccine-naive individuals, and it warrants additional studies designed to enhance DNA vaccine immunogenicity.
Raman spectroscopic study of mechanically deformed poly‐L‐alanine (1974)

Abstract Raman spectroscopy has been used in investigating the conformational transitions of poly‐ L ‐alanine (PLA) induced by mechanical deformation. We see evidence of the alpha‐helical, antiparallel beta‐sheet, and a disordered conformation in PLA. The disordered conformation has not been discussed in previous infrared and X‐ray diffraction investigations and may have local order similar to the left‐handed 3 1 poly glycine helix. The amide III mode in the Raman spectrum of PLA is more sensitive than the amide I and II modes to changes in secondary structure of the polypeptide chain. Several lines below 1200 cm −1 are conformationally sensitive and may generally be useful in the analysis of Raman spectra of proteins. A line at 909 cm −1 decreases in intensity after deformation of PLA. In general only weak scattering is observed around 900 cm −1 in the Raman spectra of antiparallel beta‐sheet polypeptides. The Raman spectra of the amide N–H deuterated PLA and poly‐ L ‐leucine (PLL) in the alpha‐helical conformation and poly‐ L ‐valine (PLV) in the beta‐sheet conformation are presented. Splitting is observed in the amide III mode of PLV and the components of this mode are assigned. The Raman spectrum of an alpha‐helical random copolymer of L ‐leucine and L ‐glutamic acid is shown to be consistent with the spectra of other alphahelical polypeptides.