gebhart/patrepeval huggingface dataset:
Molecular characterization by mass spectrometry of the human estrogen receptor ligand-binding domain expressed in Escherichia coli. (1995)

The ligand binding domain of the human estrogen receptor (hER-LBD), encompassing the sequence MDPS282AG...V595, has been expressed at high levels in Escherichia coli from a pET-23d vector, and a purified preparation has been characterized both by mass spectrometry and biochemical methods. Inclusion bodies from the bacterial expression were solubilized by sonication and the hER-LBD was purified to near homogeneity by affinity chromatography over an estradiol-Sepharose column in urea-containing buffer. This material ran as a single peak on reversed-phase HPLC, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed a band with apparent molecular mass of 31-32 kilodaltons (kDa), somewhat smaller than that expected from the construct (35.6 kDa). Edman degradation revealed a single sequence of MDPSAGDMRA, consistent with an intact N terminus. Further characterization of this material using low resolution matrix-assisted laser desorption ionization mass spectrometry indicated an apparent single protein species of average mass 33,143 daltons (Da). Detailed molecular analysis by electrospray ionization mass spectrometry, however, revealed that this purified hER-LBD preparation was actually composed of a number of both modified and unmodified LBD protein fragments between 32,900-33,400 Da. The bulk of this 33-kDa protein mixture consisted of three LBD protein fragments with C termini at Ala571 (70%), Ala569 (23%), and Ser575 (4%), with only a trace amount (3%) of the full length expressed LBD (MDPS282...V595; 35, 602 Da). These four protein species also appear to be partially chemically modified by carbamylation. The functional integrity of this hER-LBD preparation was investigated by a ligand-exchange assay, which showed that the hER-LBD retained full estradiol-binding capacity; specific, covalent labeling was also observed using either the electrophilic affinity-labeling ligand tamoxifen aziridine (TAZ) or the photoaffinity-labeling ligand hexestrol diazirine. Thus, this expressed hER-LBD preparation, while appearing nominally pure by conventional biochemical techniques and having the expected ligand-binding capacity, was shown by sensitive high resolution electrospray ionization mass spectrometry techniques to be largely truncated 20-26 amino acids from the expected C terminus and to have a substantial level of covalent modification arising from the urea.(ABSTRACT TRUNCATED AT 400 WORDS)
An Approximate Dynamic Programming Algorithm for Large-Scale Fleet Management: A Case Application (2008)

We addressed the problem of developing a model to simulate at a high level of detail the movements of over 6,000 drivers for Schneider National, the largest truckload motor carrier in the United States. The goal of the model was not to obtain a better solution but rather to closely match a number of operational statistics. In addition to the need to capture a wide range of operational issues, the model had to match the performance of a highly skilled group of dispatchers while also returning the marginal value of drivers domiciled at different locations. These requirements dictated that it was not enough to optimize at each point in time (something that could be easily handled by a simulation model) but also over time. The project required bringing together years of research in approximate dynamic programming, merging math programming with machine learning, to solve dynamic programs with extremely high-dimensional state variables. The result was a model that closely calibrated against real-world operations and produced accurate estimates of the marginal value of 300 different types of drivers.
Small Abundant DNA Binding Proteins from the Thermoacidophilic Archaeon Sulfolobus shibatae Constrain Negative DNA Supercoils (1998)

Major DNA binding proteins, designated Ssh7, were purified from the thermoacidophilic archaeon Sulfolobus shibatae. The Ssh7 proteins have an apparent molecular mass of 6.5 kDa and are similar to the 7-kDa DNA binding proteins from Sulfolobus acidocaldarius and Sulfolobus solfataricus in N-terminal amino acid sequence. The proteins constitute about 4.8% of the cellular protein. Upon binding to DNA, the Ssh7 proteins constrain negative supercoils. At the tested Ssh7/DNA mass ratios (0 to 1.65), one negative supercoil was taken up by approximately 20 Ssh7 molecules. Our results, together with the observation that the viral DNA isolated from S. shibatae is relaxed, suggest that regions of free DNA in the S. shibatae genome, if present, are highly positively supercoiled.
Off-label Use and the Medical Negligence Standard Under Minnesota Law (2005)

Who decides whether a drug can be used off-label and under what circumstances? If a physician decides to prescribe a drug off-label, what legal issues, if any, should the physician be aware of? With the increased practice of prescribing drugs for off-label use, coupled with a somewhat dated and incomplete medical negligence standard in Minnesota, the intersection of the off-label use doctrine with Minnesota’s medical negligence standard is ripe for review. This article examines the off-label use doctrine and the medical negligence standard under Minnesota law. First, the article examines what the phrase “off-label use” means. Next, the article explores the cases that have arisen in Minnesota which address medical malpractice claims arising, at least in part, because of off-label uses. Finally, the article concludes with the author’s observations about whether off-label use should be a cause for concern. In part, the author considers whether increased off-label use presents new legal issues for physicians, patients, and attorneys.
Mutation in the tau gene in familial multiple system tauopathy with presenile dementia (1998)

Familial multiple system tauopathy with presenile dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose genetic basis is unknown. We now report a G to A transition in the intron following exon 10 of the gene for microtubule-associated protein tau in familial MSTD. The mutation is located at the 3' neighboring nucleotide of the GT splice-donor site and disrupts a predicted stem-loop structure. We also report an abnormal preponderance of soluble tau protein isoforms with four microtubule-binding repeats over isoforms with three repeats in familial MSTD. This most likely accounts for our previous finding that sarkosyl-insoluble tau protein extracted from the filamentous deposits in familial MSTD consists only of tau isoforms with four repeats. These findings reveal that a departure from the normal ratio of four-repeat to three-repeat tau isoforms leads to the formation of abnormal tau filaments. The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene. This work has major implications for Alzheimer's disease and other tauopathies.
The absence of introns within a human fibroblast interferon gene (1981)

Experiments in which immobilised restriction fragments of genomic DNA were hybridised with a cloned human fibroblast interferon cDNA indicate that the homologous chromosomal genes exist in only one basic arrangement. This is in marked contrast to recent studies by Nagata et al. (1) showing that there are at least eight gene arrangements for human leukocyte interferon. Having isolated a chromosomal human fibroblast interferon gene from a gene bank, we conclude from nucleotide sequencing studies that there is a complete absence of introns within the RNA-coding region. In view of a similar observation recently made for a human leukocyte interferon gene (1), it would appear as if interferon genes in general are unlike the vast majority of eukaryote genes in this respect.
Solubilization of Nonaqueous Phase Liquid Hydrocarbons in Micellar Solutions of Dodecyl Alcohol Ethoxylates (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolubilization of Nonaqueous Phase Liquid Hydrocarbons in Micellar Solutions of Dodecyl Alcohol EthoxylatesMamadou S. Diallo, Linda M. Abriola, and Walter J. WeberCite this: Environ. Sci. Technol. 1994, 28, 11, 1829–1837Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/es00060a012https://doi.org/10.1021/es00060a012research-articleACS PublicationsRequest reuse permissionsArticle Views506Altmetric-Citations105LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. (1993)

To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice. These mice do not produce detectable amounts of either TGF-beta 1 RNA or protein. After normal growth for the first 2 weeks they develop a rapid wasting syndrome and die by 3-4 weeks of age. Pathological examination revealed an excessive inflammatory response with massive infiltration of lymphocytes and macrophages in many organs, but primarily in heart and lungs. Many lesions resembled those found in autoimmune disorders, graft-vs.-host disease, or certain viral diseases. This phenotype suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues.
Epitope Discovery Using Monoclonal Antibodies and Phage Peptide Libraries (1999)

Phage display is a biological system which facilitates the cloning and rapid selection of peptides from large combinatorial libraries. In comparison to the chemical combinatorial approach, the advantages of phage display lie in its simplicity and replicability. While phage display has many diverse applications, this review will focus on the use of phage peptide libraries to discover epitopes recognised by monoclonal antibodies. As monoclonal antibodies are useful tools for the detection of proteins and for the investigation of molecular interactions, the identification of their epitopes will serve to elucidate the structure and function of proteins, as well as aid in the discovery of new drugs and the development of vaccines.
Concentration of Mn-superoxide dismutase in serum in acute myocardial infarction (1991)

Serum concentrations of manganese-containing superoxide dismutase (Mn-SOD; EC 1.15.1.1), a mitochondrial enzyme present in high concentrations in the heart, were measured successively by enzyme immunoassay in 18 patients with acute myocardial infarction (AMI) and in eight with angina pectoris. Results were compared with creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB) concentrations in the same specimens. The mean (and SD) serum Mn-SOD concentration in 120 healthy adults was 77.5 (18) micrograms/L. Mn-SOD concentrations exceeding 150 micrograms/L (greater than mean + 4 SD) were considered above-normal. In patients with AMI, the Mn-SOD concentration was 80 (16.8) micrograms/L on admission and increased gradually after the first hospital day. The peak, 260 (109) microgram/L, occurred on the fourth hospital day, at which time the Mn-SOD concentrations in all AMI patients were above normal. Thereafter the Mn-SOD concentration decreased slowly, but still was above normal in 14 of 18 patients on the seventh hospital day. On the other hand, in patients with angina pectoris, the Mn-SOD concentration was 78 (11) micrograms/L on admission and did not increase significantly [peak value 97.5 (42) micrograms/L on the fourth hospital day]. The serum concentration of Mn-SOD is a potentially useful marker for estimating cardiac mitochondrial damage and for diagnosing AMI, especially in the late phase.
ocs element promoter sequences are activated by auxin and salicylic acid in Arabidopsis. (1994)

ocs elements are a group of promoter elements that have been exploited by two distinct groups of plant pathogens, Agrobacterium and certain viruses, to express genes in plants. We examined the activity of single and multiple ocs elements linked to a minimal plant promoter and the uidA reporter gene in transgenic Arabidopsis. beta-Glucuronidase activity was detected only in root tips and in callus tissue after auxin treatment. A more sensitive assay revealed that auxin treatment also increased ocs element activity in aerial parts of the plant, although the absolute levels of ocs element activity were greater in roots. The response of ocs elements to exogenous auxin began within 1 h. Salicylic acid, a disease-resistance signal in plants, also increased ocs element activity in both roots and aerial parts of the plant. The question of whether the induction in ocs element activity is mediated through auxin and/or salicylic acid signal transduction pathways or is part of a more general stress response is discussed.
Comparative proteomic analyses of two reovirus T3D subtypes and comparison to T1L identifies multiple novel proteins in key cellular pathogenic pathways (2015)

Viruses induce changes in the host to facilitate replication and evade the immune response. These changes are reflected by the host's proteome, including differences in protein abundance. Focusing on up and down regulated proteins after a virus infects the cell will lead to a characterization of the host response to infection, and may give insight into how viruses modulate proteins to evade host defense responses. We previously used SILAC to examine host proteomic changes in protein abundance in HEK293 cells infected with reovirus type 1, strain Lang (T1L). For the present study, we extended this analysis by determining cell protein alterations induced by two different reovirus subtypes, a less pathogenic type 3 Dearing (T3D(F)) isolate, and a more pathogenic isolate named T3D(C) that is presently in clinical trials as an anti-cancer oncolytic agent. This comparison of host proteome regulation showed that T3D(C) had a more marked effect on DNA replication proteins, recombination and repair, as well as immunological, apoptotic, and survival cell functions. We also identified several proteins not previously identified in any virus infection; branched chain amino-acid transaminase 2 (BCAT), paternally expressed 10 (PEG10), target of myb1 (TOM1), histone cluster 2 H4b (HIST2H4B) and tubulin beta 4B (TUBB4B).
Phase I/II study of PHY906/capecitabine in advanced hepatocellular carcinoma. (2009)

PHY906 is a Chinese medicine formula with claims for the treatment of severe gastrointestinal distress. PHY906 enhanced the therapeutic index of various chemotherapeutic agents in human hepatocellular carcinoma xenografts. Accordingly, here a phase I/II clinical study was conducted with the combination of capecitabine in patients with advanced, unresectable hepatocellular carcinoma. More than 60% of patients had either stable disease or better after two treatment cycles. Median overall survival was 9.2 months. Asian patients had a higher median overall survival (16.5 months) than non-Asian patients (6.2 months, p=0.03). Patients' quality of life did not deteriorate significantly during treatment. This finding supported further investigation of PHY906 as an adjuvant therapy of capecitabine in a larger hepatocellular cancer population.
Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2 (1998)

The INK4a-ARF locus encodes two proteins, p16(INK4a) and p19(ARF), that restrain cell growth by affecting the functions of the retinoblastoma protein and p53, respectively. Disruption of this locus by deletions or point mutations is a common event in human cancer, perhaps second only to the loss of p53. Using insect cells infected with baculovirus vectors and NIH 3T3 fibroblasts infected with ARF retrovirus, we determined that mouse p19(ARF) can interact directly with p53, as well as with the p53 regulator mdm2. ARF can bind p53-DNA complexes, and it depends upon functional p53 to transcriptionally induce mdm2 and the cyclin-dependent kinase inhibitor p21(Cip1), and to arrest cell proliferation. Binding of p19(ARF) to p53 requires the ARF N-terminal domain (amino acids 1-62) that is necessary and sufficient to induce cell cycle arrest. Overexpression of p19(ARF) in wild type or ARF-null mouse embryo fibroblasts increases the half-life of p53 from 15 to approximately 75 min, correlating with an increased p53-dependent transcriptional response and growth arrest. Surprisingly, when overexpressed at supra-physiologic levels after introduction into ARF-null NIH 3T3 cells or mouse embryo fibroblasts, the p53 protein is handicapped in inducing this checkpoint response. In this setting, reintroduction of p19(ARF) restores p53's ability to induce p21(Cip1) and mdm2, implying that, in addition to stabilizing p53, ARF modulates p53-dependent function through an additional mechanism.
Fine elasticity imaging utilizing the iterative RF-echo phase matching method (1999)

To non-invasively quantify elasticity of soft tissue, we previously developed the iterative two-dimensional (2-D) rf-echo phase matching method for accurately measuring a 2-D displacement vector field generated in vivo in soft tissue during acquisition of two successive rf-echo data frames. We also developed a stable method for uniquely reconstructing a shear modulus distribution using strains derived from the measurement data. However, as in our measurement method a displacement is determined by using the phase characteristics of the finite local echo data as the index to iteratively search for the corresponding local data, change of the local phase characteristics due to tissue deformation deteriorates the accuracy of the determination. Thus, we improve the previous method such that, in principle, the displacement can be determined using an infinitesimal phase characteristics. That is, we incorporate an effective mechanism into the previous iterative phase matching scheme: the local size is made suitably smaller during the iterative phase matching. The demonstrated ability of measurement and reconstruction in simulation, and experiments on in vitro in pork rib and in vivo in breast tissue, shows this refinement allows not only better spatial resolution of the shear modulus image but also improved accuracy, and indicates that the improved method has a high potential to be applied for various soft tissues.
Mitral Transcatheter Technologies (2013)

Mitral valve regurgitation (MR) is often diagnosed in patients with heart failure and is associated with worsening of symptoms and reduced survival. While surgery remains the gold standard treatment in low-risk patients with degenerative MR, in high-risk patients and in those with functional MR, transcatheter procedures are emerging as an alternative therapeutic option. MitraClip(®) is the device with which the largest clinical experience has been gained to date, as it offers sustained clinical benefit in selected patients. Further to MitraClip implantation, several additional approaches are developing, to better match with the extreme variability of mitral valve disease. Not only repair is evolving, initial steps towards percutaneous mitral valve implantation have already been undertaken, and initial clinical experience has just started.
Early T-Cell Responses to Dengue Virus Epitopes in Vietnamese Adults with Secondary Dengue Virus Infections (2005)

T-cell responses to dengue viruses may be important in both protective immunity and pathogenesis. This study of 48 Vietnamese adults with secondary dengue virus infections defined the breadth and magnitude of peripheral T-cell responses to 260 overlapping peptide antigens derived from a dengue virus serotype 2 (DV2) isolate. Forty-seven different peptides evoked significant gamma interferon enzyme-linked immunospot (ELISPOT) assay responses in 39 patients; of these, 34 peptides contained potentially novel T-cell epitopes. NS3 and particularly NS3200-324 were important T-cell targets. The breadth and magnitude of ELISPOT responses to DV2 peptides were independent of the infecting dengue virus serotype, suggesting that cross-reactive T cells dominate the acute response during secondary infection. Acute ELISPOT responses were weakly correlated with the extent of hemoconcentration in individual patients but not with the nadir of thrombocytopenia or overall clinical disease grade. NS3556-564 and Env414-422 were identified as novel HLA-A*24 and B*07-restricted CD8+ T-cell epitopes, respectively. Acute T-cell responses to natural variants of Env414-422 and NS3556-564 were largely cross-reactive and peaked during disease convalescence. The results highlight the importance of NS3 and cross-reactive T cells during acute secondary infection but suggest that the overall breadth and magnitude of the T-cell response is not significantly related to clinical disease grade.
Effect of Surface Elasticity on Ostwald Ripening in Emulsions (2001)

The coarsening of droplets in an emulsion with a size distribution that initially is given by the Lifshitz−Slyozov−Wagner (LSW) distribution is studied by means of numerical calculations taking into account elastic interfacial behavior. Droplets smaller than the critical radius will shrink while droplets larger than the critical radius will grow. For a zero interfacial elasticity the stationary LSW distribution is obtained and its coarsening rate matches theoretical values. The critical droplet radius, number-averaged droplet radius, and volume-surface-averaged droplet radius increase with time. Low interfacial elasticity with respect to initial interfacial tension causes the initial LSW distribution to become bimodal. The size distribution of the coarsening peak can still be described by the LSW distribution. The smaller peak that accumulates in time has an average radius that depends on the ratio between the interfacial elastic modulus and the interfacial tension. For large ratios (E/σ > 1), the system goes within a short time to a stable situation without changes in particle size with time.
Microvascular anastomosis at 30-50× magnifications (super-microvascular anastomosis) in neurosurgery (2011)

It is obvious that practical final magnifications of more than 30 × in neurosurgery would be super-magnified operative views. Microvascular anastomosis at 30 - 50 × magnifications (super-microvascular anastomosis) can help neurosurgeons to improve their skills, with good visualization, and to be safe and accurate when conducting cerebral revascularization in various situations.