gebhart/patrepeval huggingface dataset:
Drug Treatment for Multidrug-Resistant Acinetobacter Baumannii Infections (2008)

Acinetobacter baumannii has emerged in the last decades as a major cause of healthcare-associated infections and nosocomial outbreaks. Multidrug-resistant (MDR) A. baumannii is a rapidly emerging pathogen in healthcare settings, where it causes infections that include bacteremia, pneumonia, meningitis, and urinary tract and wound infections. Antimicrobial resistance poses great limits for therapeutic options in infected patients, especially if the isolates are resistant to the carbapenems. Other therapeutic options include sulbactam, aminoglycosides, polymixyns and tigecycline. The discovery of new therapies coupled with the development of controlled clinical trial antibiotic testing combinations and the prevention of transmission of MDR Acinetobacter infection are essential to face this important hospital problem.
Mutations as Missing Data: Inferences on the Ages and Distributions of Nonsynonymous and Synonymous Mutations (2001)

This article describes a new Markov chain Monte Carlo (MCMC) method applicable to DNA sequence data, which treats mutations in the genealogy as missing data. The method facilitates inferences regarding the age and identity of specific mutations while taking the full complexities of the mutational process in DNA sequences into account. We demonstrate the utility of the method in three applications. First, we demonstrate how the method can be used to make inferences regarding population genetical parameters such as theta (the effective population size times the mutation rate). Second, we show how the method can be used to estimate the ages of mutations in finite sites models and for making inferences regarding the distribution and ages of nonsynonymous and synonymous mutations. The method is applied to two previously published data sets and we demonstrate that in one of the data sets the average age of nonsynonymous mutations is significantly lower than the average age of synonymous mutations, suggesting the presence of slightly deleterious mutations. Third, we demonstrate how the method in general can be used to evaluate the posterior distribution of a function of a mapping of mutations on a gene genealogy. This application is useful for evaluating the uncertainty associated with methods that rely on mapping mutations on a phylogeny or a gene genealogy.
A synthetic vaccine constructed by copolymerization of B and T cell determinants (1987)

Synthetic vaccines are based on the identification of short peptide sequences responsible for inducing a protective immune response. These sequences could contain B and/or T cell determinants. In this study, we have examined the recognition by B and T mouse lymphocytes of several synthetic peptides corresponding to regions of a bacterial and two viral proteins. These include a streptococcal S-34 peptide, H(99-121) and two other synthetic hepatitis B virus surface peptides. A lymph node proliferation assay was employed to detect T cell determinants. Limiting dilution analysis was used to estimate the frequency of clonal precursor B cells specific for an antigenic determinant. This study indicates that the synthetic hepatitis B virus surface peptides are recognized by B cells but not by T cells, whereas the S-34 peptide possesses both B and T epitopes. The copolymerization of the B determinant H(99-121) with S-34 has conferred immunogenicity to the H(99-121) peptide. After copolymerization, the synthetic hybrid molecule retained the S-34 T epitope and acquired a new determinant recognized by T cells. These results demonstrate that synthetic vaccines could be constructed by appropriate selection and organization of B and T determinants.
Stress granules: sites of mRNA triage that regulate mRNA stability and translatability (2002)

Mammalian stress granules (SGs) are cytoplasmic domains into which mRNAs are sorted dynamically in response to phosphorylation of eukaryotic initiation factor (eIF) 2alpha, a key regulatory step in translational initiation. The activation of one or more of the eIF2alpha kinases leads to SG assembly by decreasing the levels of eIF2-GTP-tRNA(Met), the ternary complex that is normally required for loading the initiator methionine onto the 48 S preinitiation complex to begin translation. This stress-induced scarcity of eIF2-GTP-tRNA(Met) allows the RNA-binding proteins TIA-1 (T-cell internal antigen-1) and TIAR (TIA-1-related protein) to bind the 48 S complex in lieu of the ternary complex, thereby promoting polysome disassembly and the concurrent routing of the mRNA into a SG. The actual formation of SGs occurs upon auto-aggregation of the prion-like C-termini of TIA-1 proteins; this aggregation is reversed in vivo by overexpression of the heat-shock protein (HSP) chaperone HSP70. Remarkably, HSP70 mRNA is excluded from SGs and is preferentially translated during stress, indicating that the RNA composition of the SG is selective. Moreover, the effects of HSP70 on TIA aggregation suggest a feedback loop whereby HSP70 synthesis is auto-regulated. Proteins that promote mRNA stability [e.g. HuR (Hu protein R)] and destabilize mRNA [i.e. tristetraprolin (TTP)] are also recruited to SGs, suggesting that SGs effect a process of mRNA triage, by promoting polysome disassembly and routing mRNAs to cytoplasmic domains enriched for HuR and TTP. This model reveals connections between the eIF2alpha kinase system, mRNA stability and cellular chaperone levels.
Correction: Directed In Vitro Myogenesis of Human Embryonic Stem Cells and Their In Vivo Engraftment (2013)

[This corrects the article on p. e72023 in vol. 8.].
Structured support versus learner choice via the World Wide Web (WWW): where is the payoff? (2000)

In this exploratory study, students were given the choice of two forms of participation in a course. One form involved structured instructor support, in which the students were required to sub-mit work via the WWW for regular feedback from the instructor and also to make use of various WWW-based tools in the differ-ent phases of their work. The other form of participation made the same possibilities and tools available but did not require or structure their use. Although this exploratory study was not car-ried out under strict experimental conditions, the results of com-paring the 18 students in the structured-support approach with the 7 students in the learner-choice form showed that, although students in the structured-support variant spent twice as much time on the course as did students in the learner-choice variant, there was no significant difference between the groups in terms of overall performance on the final examination and little differ-ence in attitudes. Dividing the test questions into knowledge-type and transfer-type questions did show a marginally signifi-cant (p=.054) difference in performance on transfer-type ques-tions favouring the structured-support group, although these re-sults are no more than pointers for further research given the ex-ploratory nature of the study. Reflections based on the study are presented, particularly related to the costs and benefits of the two forms of participation in terms of instructor and learner time.
Elementary matrix theory (1980)

The usefulness of matrix theory as a tool in disciplines ranging from quantum mechanics to psychometrics is widely recognized, and courses in matrix theory are increasingly a standard part of the undergraduate curriculum.This outstanding text offers an unusual introduction to matrix theory at the undergraduate level. Unlike most texts dealing with the topic, which tend to remain on an abstract level, Dr. Eves' book employs a concrete elementary approach, avoiding abstraction until the final chapter. This practical method renders the text especially accessible to students of physics, engineeri
Stimulation of Swine Growth by Porcine Growth Hormone1 (1985)

Highly purified porcine growth hormone (pGH; USDA-B1) was administered by im injection (22 micrograms X kg body weight-1 X d-1) to rapidly growing Yorkshire barrows for 30 d. Growth hormone significantly increased growth rate (10%), feed efficiency (4%), cartilage growth and muscle mass. However, pGH did not affect carcass adipose tissue mass. Intramuscular lipid content of the longissimus was increased 50% by pGH administration. Plasma pGH concentration was elevated (7- to 11-fold) for 3 to 5 h post-injection. Chronic administration of pGH depressed pituitary GH content and concentration approximately 45%. No GH antibodies were detected in the plasma of GH-treated swine. Plasma somatomedin-C concentration was increased 55% by GH treatment 3 h post-injection. Plasma glucose and insulin concentrations were both significantly increased in GH-treated swine, suggesting that the animals had developed a state of insulin resistance. Plasma-free fatty acid concentration tended to be higher in GH-treated animals. Treatment of swine with pGH significantly decreased plasma blood urea nitrogen. Assessment of animal health during the trial and postmortem indicated that pGH administration did not have any adverse effects. In summary, treatment of young, rapidly growing swine with pGH stimulated growth performance without affecting animal health or inducing the production of GH antibodies.
Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning (1998)

Mesodermal development is a multistep process in which cells become increasingly specialized to form specific tissue types. In Drosophila and mammals, proper segregation and patterning of the mesoderm involves the bHLH factor Twist. We investigated the activity of a Twist-related factor, CeTwist, during Caenorhabditis elegans mesoderm development. Embryonic mesoderm in C. elegans derives from a number of distinct founder cells that are specified during the early lineages; in contrast, a single blast cell (M) is responsible for all nongonadal mesoderm formation during postembryonic development. Using immunofluorescence and reporter fusions, we determined the activity pattern of the gene encoding CeTwist. No activity was observed during specification of mesodermal lineages in the early embryo; instead, the gene was active within the M lineage and in a number of mesodermal cells with nonstriated muscle fates. A role for CeTwist in postembryonic mesodermal cell fate specification was indicated by ectopic expression and genetic interference assays. These experiments showed that CeTwist was responsible for activating two target genes normally expressed in specific subsets of nonstriated muscles derived from the M lineage. In vitro and in vivo assays suggested that CeTwist cooperates with the C. elegans E/Daughterless homolog in directly activating these targets. The two target genes that we have studied, ceh-24 and egl-15, encode an NK-2 class homeodomain and an FGF receptor (FGFR) homolog, respectively. Twist activates FGFR and NK-homeodomain target genes during mesodermal patterning of Drosophila and similar target interactions have been proposed to modulate mesenchymal growth during closure of the vertebrate skull. These results suggest the possibility that a conserved pathway may be used for diverse functions in mesodermal specification.
JD induced pluripotent stem cell-derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia (2012)

Cumulatively, these findings demonstrate that FH iPSC-derived hepatocytes recapitulate the complex pathophysiology of FH in culture. These results also establish that patient-specific iPSC-derived hepatocytes could be used to definitively determine the functional contribution of allelic variation in regulating lipid and cholesterol metabolism and could potentially provide a platform for the identification of novel treatments of cardiovascular disease. (HEPATOLOGY 2012).
Implantation of Cultured Preadipocyte Using Chitosan/Alginate Sponge (2007)

Alginate was a proven biocompatible biomatrice for cells but it was known not to provide a proper microenvironment needed for the proliferation of cells because of its anionic property, which caused its low affinity for cells. Water-soluble chitosan was well known as wound healing material and it also had cationic property which helped cell-to-matrix adhesion. The purpose of this study is to assess the ability of a chitosan/alginate mixed sponge as a scaffold for preadipocytes to serve as a biological implant for soft tissue augmentation. Chitosan/alginate and calcium alginate sponges were made by lyophilizing of alginate with water-soluble chitosan mixture and with calcium chloride mixture, respectively, and those were observed by SEM. Preadipocytes seeded in those sponges were cultured for 2 weeks. In vivo study was designed that chitosan/alginate sponges with and without preadipocytes were implanted subcutaneously into nude mouse. Chitosan/alginate and calcium alginate sponges which had highly porosity and 50-200㎛ pore size. In the chitosan/alginate sponge, the levels of DNA amount were significantly higher than those in calcium alginate sponge (P&lt;0.05). In both groups, they increased progressively with time. On the in vivo study, it was observed that adipose tissue layer in the margin of chitosan/alginate sponge on the 2 weeks after implantation of nude mouse. On the 8 weeks after implantation, thick layer of adipose tissue and neovascularization were observed in the chitosan/alginate sponge. Consequently, chitosan/alginate sponge provided proper microenvironment to human preadipocyte, increased the cell proliferation and maintained the pore that offered neovascularization, so turned out to be effective form of fat transplantation for soft tissue augmentation and reconstruction.
Wet etching of gold films compatible with high T c superconducting thin films (1991)

We report a wet etch process for selective patterning or removing gold (Au) layers on top of high Tc YBa2Cu3O7 (YBCO) thin-film structures. As an etchant for Au, an aqueous solution of potassium iodide (KI) and iodide (I) was chosen. This etchant does not degrade YBCO or any commonly used substrate materials (SrTiO3, MgO, zirconia, and NdGaO3). This KI and I solution gives convenient etch rates of 200–300 Å/min and easily stops on the YBCO due to its high selectivity. Using this wet chemical etching process, we have fabricated structures with better than 1 μm resolution. We have found this etchant to be very useful for secondary electron microscopy analysis of high Tc device structures.
Cloning and expression of a widely expressed receptor tyrosine phosphatase. (1990)

We describe the identification of a widely expressed receptor-type (transmembrane) protein tyrosine phosphatase (PTPase; EC 3.1.3.48). Screening of a mouse brain cDNA library under low-stringency conditions with a probe encompassing the intracellular (phosphatase) domain of the CD45 lymphocyte antigen yielded cDNA clones coding for a 794-amino acid transmembrane protein [hereafter referred to as receptor protein tyrosine phosphatase alpha (R-PTP-alpha)] with an intracellular domain displaying clear homology to the catalytic domains of CD45 and LAR (45% and 53%, respectively). The 142-amino acid extracellular domain (including signal peptide) of R-PTP-alpha is marked by a high serine/threonine content (32%) as well as eight potential N-glycosylation sites but displays no similarity to known proteins. Genetic mapping assigns the gene for R-PTP-alpha to mouse chromosome 2, closely linked to the Il-1a and Bmp-2a loci. The corresponding mRNA (3.0 kilobases) is expressed in most murine tissues and most abundantly expressed in brain and kidney. Antibodies against a synthetic peptide of R-PTP-alpha identified a 130-kDa protein in cells transfected with the R-PTP-alpha cDNA.
Reversible Three-Electron Redox Behaviors of FeF3 Nanocrystals as High-Capacity Cathode-Active Materials for Li-Ion Batteries (2010)

Three types of FeF3 nanocrystals were synthesized by different chemical routes and investigated as a cathode-active material for rechargeable lithium batteries. XRD and TEM analyses revealed that the as-synthesized FeF3 samples have a pure ReO3-type structure with a uniformly distributed crystallite size of ∼10 to 20 nm. Charge−discharge experiments in combination with cyclic voltammetric and XRD evidence demonstrated that the FeF3 in the nanocomposite electrode can realize a reversible electrochemical conversion reaction from Fe3+ to Fe0 and vice versa, enabling a complete utilization of its three-electron redox capacity (∼712 mAh·g−1). Particularly, the FeF3/C nanocomposites can be well cycled at very high rates of 1000−2000 mA·g−1, giving a considerably high capacity of ∼500 mAh·g−1. These results seem to indicate that the electrochemical conversion reaction can not only give a high capacity but also proceed reversibly and rapidly at room temperature as long as the electroactive FeF3 particles are sufficiently downsized, electrically wired, and well-protected from aggregation. The high-rate capability of the FeF3/C nanocomposite also suggests its potential applications for high-capacity rechargeable lithium batteries.
Short hairpin RNA-directed cytosine (CpG) methylation of the RASSF1A gene promoter in HeLa cells (2005)

Methylation of cytosines in CpG motifs is an important mechanism for epigenetic regulation of gene expression in mammalian cells. The initiating event(s) for de novo methylation in mammalian cells, particularly in cancer, is unknown. In plants, short RNAs homologous to DNA sequences are known to initiate de novo methylation. To investigate whether short hairpin RNAs (shRNAs) may also serve as initiators for de novo methylation in human cells we have expressed short hairpin RNAs complementary to the CpG island including the promoter and early transcribed regions of the human RASSF1A gene. RASSF1A encodes a putative tumor suppressor that is hypermethylated in a variety of human cancers, whereas in some human cell lines, such as HeLa, RASSF1A is unmethylated and transcriptionally active. We demonstrate that shRNAs complementary to the RASSF1A promoter or early transcribed regions can direct low levels of de novo DNA methylation and partial gene silencing in HeLa cells. In contrast, an shRNA harboring four central mismatches with the target cannot direct such methylation. The results presented suggest provocative potential mechanisms for transcriptional gene silencing via DNA methylation in cancer cells.
Implications of receptor-mediated endocytosis and intracellular trafficking dynamics in the development of antibody drug conjugates (2013)

The use of antibody-drug conjugates (ADCs) as a therapeutic platform to treat cancer has recently gained substantial momentum. This therapeutic modality has the potential to increase the efficacy and reduce the systemic toxicity associated with current therapeutic regimens. The efficacy of ADCs, however, relies on the proper exploitation of intracellular sorting dynamics of the antigen as well as the specificity, selectivity and pharmacokinetic properties of the antibody itself. Our understanding of endocytosis and endosomal trafficking of receptors has appreciably increased in recent years, as improvements in the assays used to study these events have resolved many of the molecular mechanisms regulating these processes. As a result, we now have the knowledge necessary to exploit these pathways efficiently to improve the efficacy of antibody-based therapy. This review discusses some recent studies that have explored how endo/lysosomal dynamics can affect the efficacy of engineered therapeutic antibodies, including ADCs.
Decreased Expression of Tumor Necrosis Factor-α-Stimulated Gene 6 in Cumulus Cells of the Cyclooxygenase-2 and EP2 Null Mice (2003)

Ovulation, the release of fertilizable oocytes from mature follicles, involves tissue remodeling and increased prostaglandin (PG) signaling. Cyclooxygenase (COX)-2 is the rate-limiting enzyme during PG synthesis. Female mice null for either COX-2 or the PGE(2) receptor EP2 are infertile, show decreased ovulation, and exhibit abnormal cumulus expansion. Cumulus expansion is the production of a complex extracellular matrix surrounding the cumulus-oocyte complex (COC). Matrix components consist of hyaluronan, proteoglycans, and proteins with hyaluronan binding domains. One such hyaluronan binding protein is TNFalpha-stimulated gene 6 (TSG-6). By various methods, we show induction of TSG-6 and hyaluronan synthase-2 mRNA in ovaries of mice treated with pregnant mare serum gonadotropin and human chorionic gonadotropin. By in situ hybridization, we show that both genes are expressed in periantral mural granulosa cells and cumulus cells of the mouse ovary. Notably, RT-PCR and in situ hybridization show that TSG-6 mRNA but not hyaluronan synthase-2 mRNA expression is selectively reduced in cumulus cells of COX-2 and EP2 null mice. Western analysis further confirms that TSG-6 protein is reduced in isolated COCs but remains covalently associated with inter alpha-trypsin inhibitor in COX-2 null mice. These observations identify TSG-6 as a target of PG action and show that its production in ovulatory follicles is associated with proper formation of the cumulus-derived extracellular matrix.
Involvement of N-terminal-extended Form of Sphingosine Kinase 2 in Serum-dependent Regulation of Cell Proliferation and Apoptosis (2005)

Sphingosine kinase (SPHK) 1 is implicated in the regulation of cell proliferation and anti-apoptotic processes by catalyzing the formation of an important bioactive messenger, sphingosine 1-phosphate. Unlike the proliferative action of SPHK1, another isozyme, SPHK2, has been shown to possess anti-proliferative or pro-apoptotic action. Molecular mechanisms of SPHK2 action, however, are largely unknown. The present studies were undertaken to characterize the N-terminal-extended form of SPHK2 (SPHK2-L) by comparing it with the originally reported form, SPHK2-S. Real-time quantitative PCR analysis revealed that SPHK2-L mRNA is the major form in several human cell lines and tissues. From sequence analyses it was concluded that SPHK2-L is a species-specific isoform that is expressed in human but not in mouse. At the protein level it has been demonstrated by immunoprecipitation studies that SPHK2-L is the major isoform in human hepatoma HepG2 cells. SPHK2-L, when expressed in human embryonic kidney (HEK) 293 cells, did not show any inhibition of DNA synthesis in the presence of serum, whereas it showed marked inhibition in the absence of serum. Moreover, serum deprivation resulted in the translocation of SPHK2-L into the nuclei. In addition, serum deprivation induced SPHK2-L expression in HEK293 cells. Furthermore, suppression of SPHK2 by small interfering RNA treatment prevented serum deprivation- or drug-induced apoptosis in HEK293 cells. Taken together, these results indicate that a major form of SPHK2 splice variant, SPHK2-L, in human cells does not inhibit DNA synthesis under normal conditions and that SPHK2-L accumulation in the nucleus induced by serum deprivation may be involved in the cessation of cell proliferation or apoptosis depending on the cell type.
Cell therapy of primary myopathies. (2005)

Mesoangioblasts are multipotent progenitors of mesodermal tissues. In vitro mesoangioblasts differentiate into many mesoderm cell types, such as smooth, cardiac and striated muscle, bone and endothelium. After transplantation mesoangioblasts colonize mostly mesoderm tissues and differentiate into many cell types of the mesoderm. When delivered through the arterial circulation, mesoangioblasts significantly restore skeletal muscle structure and function in a mouse model of muscular dystrophy. Their ability to extensively self-renew in vitro, while retaining multipotency, qualifies mesoangioblasts as a novel class of stem cells. Phenotype, properties and possible origin of mesoangioblasts are addressed in the first part of this paper. In the second part we will focus on the cell therapy approach for the treatment of Muscular Dystrophy and we will describe why mesangioblasts appear to be promising candidates for this strategy.