gebhart/patrepeval huggingface dataset:
Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats (2005)

The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in orchidectomized rats. In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone, and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 wk. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT-treated (3 mg/kg) animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights more than 2-fold greater than that observed in intact controls, whereas S-4 (3 mg/kg) returned these androgenic organs to only 16 and 17%, respectively, of the control levels. S-4 (3 and 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary and significantly decreased plasma LH and FSH levels in castrated animals in a dose-dependent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue-selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.
Expression of folate binding protein as a prognostic factor for response to platinum-containing chemotherapy and survival in human ovarian cancer (1998)

Overexpression of the folate binding protein (FBP) is a common feature in epithelial ovarian cancer, but its prognostic significance is not clearly understood. We investigated whether FBP in epithelial ovarian cancer specimens is a predictor of response to chemotherapy and survival. Between 1990 and 1995, 99 patients with epithelial ovarian cancer underwent primary surgery and were treated with chemotherapeutic regimens including platinum derivatives. First-line chemotherapy was performed in 58 patients with residual disease and in 41 patients without residual disease after primary laparotomy. FBP expression level was determined in frozen specimens by cyto-fluorimetric assay using the MOv 18 monoclonal antibody (MAb). Association of FBP fluorescence index (FI) with clinical characteristics, response to chemotherapy, and survival was studied by univariate and multivariate analysis. In the 58 patients with residual disease after primary surgery, failure to respond to chemotherapy (complete or partial remission) was about 15-fold higher (95% confidence interval, 2.96-77.43) when tumors had FBP FI above the median value (FBP FI = 3.25). FBP FI was not a predictor of survival in the entire series of tumors (99 patients). However, in the subgroup of 58 patients with residual disease after primary surgery, survival analysis confirmed the disadvantage observed with respect to response to chemotherapy in patients expressing FBP FI above the median value (hazard ratio 2.01; 95% confidence interval 0.95-4.24). In conclusion, higher levels of FBP expression might be a predictor of chemotherapy response failure in ovarian cancer. In patients with residual disease after primary surgery, FBP FI could represent a valuable prognostic marker for survival.
Cellular immunity to Bacteroides fragilis capsular polysaccharide. (1982)

The polysaccharide capsule of Bacteroides fragilis has been shown to be important in the virulence of the organism. The capsular polysaccharide (CP) of B. fragilis has been extensively purified. Using a murine model of intraabdominal abscess formation, we have been able to demonstrate cellular immunity to the capsular polysaccharide of B. fragilis. Immunization of C57BL/10J mice with the CP over 5 wk prevents abscess formation when the mice are challenged with B. fragilis intraperitoneally. This immunity can be transferred to naive mice with spleen cells from immune animals. The immune cells bear Thy-1.2 and Ly-2.2 antigens. The immune response has been shown to be antigen specific, but not H-2 restricted. The possibility that these immune cells are suppressor T cells is discussed. The experimental system presented provides a model for the examination of the cellular interactions responsible for abscess formation and the cellular response to bacterial pathogens.
High-power coherent diode lasers (1991)

Diffraction-limited beam operation at high output power levels (0.5 W cw and 1.5 W pulsed) has been demonstrated from resonant-optical-waveguide (ROW) array structures. Uniphase mode operation is achieved without the need for active phase control. As a result, a reliable monolithic device capable of watt-range coherent output power is obtained.
The Pathogenesis and Treatment of Kidney Stones (1992)

ABOUT three fourths of all kidney stones are composed of calcium oxalate1; most calcium oxalate stones also contain a small amount of hydroxyapatite, and 10 to 12 percent contain some uric acid.2 Ten to 20 percent of stones contain struvite (magnesium ammonium phosphate) produced by a urinary tract infection with bacteria that express the enzyme urease.3 Five percent of stones are pure uric acid, 5 percent contain more than 50 percent hydroxyapatite or calcium monohydrogen phosphate (brushite), and less than 1 percent are composed of cystine. Whereas most calcium oxalate stones are less than 2 cm in diameter, struvite, . . .
Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans (2008)

The vanilloid receptor TRPV1 has been identified as a molecular target for the treatment of pain associated with inflammatory diseases and cancer. Hence, TRPV1 antagonists have been considered for therapeutic evaluation in such diseases. During Phase I clinical trials with AMG 517, a highly selective TRPV1 antagonist, we found that TRPV1 blockade elicited marked, but reversible, and generally plasma concentration-dependent hyperthermia. Similar to what was observed in rats, dogs, and monkeys, hyperthermia was attenuated after repeated dosing of AMG 517 (at the highest dose tested) in humans during a second Phase I trial. However, AMG 517 administered after molar extraction (a surgical cause of acute pain) elicited long-lasting hyperthermia with maximal body temperature surpassing 40 degrees C, suggesting that TRPV1 blockade elicits undesirable hyperthermia in susceptible individuals. Mechanisms of AMG 517-induced hyperthermia were then studied in rats. AMG 517 caused hyperthermia by inducing tail skin vasoconstriction and increasing thermogenesis, which suggests that TRPV1 regulates vasomotor tone and metabolic heat production. In conclusion, these results demonstrate that: (a) TRPV1-selective antagonists like AMG 517 cannot be developed for systemic use as stand alone agents for treatment of pain and other diseases, (b) individual susceptibility influences magnitude of hyperthermia observed after TRPV1 blockade, and (c) TRPV1 plays a pivotal role as a molecular regulator for body temperature in humans.
COVID-19 and telehealth (2021)

In the third and final article in this series, patient and provider dynamics are explored, built from real-life telehealth experiences. The Four Habits Model is utilized to examine the virtual visit.
Blue- and green-noise halftoning models (2003)

In this article, we review the spatial and spectral characteristics of blue- and green-noise halftoning models. In the case of blue noise, dispersed-dot dither patterns are constructed by isolating minority pixels as homogeneously as possible, and by doing so, a pattern composed exclusively of high-frequency spectral components is produced. Blue-noise halftoning is preferred for display devices that can accommodate isolated dots such as various video displays and some print technologies such as ink-jet. For print marking engines that cannot support isolated pixels, dispersed-dot halftoning is inappropriate. For such cases, clustered-dot halftoning is used to avoid dot-gain instability. Green-noise halftones are clustered-dot, blue-noise patterns. Such patterns enjoy the blue-noise properties of homogeneity and lack low-frequency texture but have clusters of minority pixels on blue-noise centers. Green noise is composed exclusively of midfrequency spectral components. In addition to the basic spatial and spectral characteristics of the halftoning models, this article also reviews some of the earlier work done to improve error diffusion as a noise generator. We also discuss processes to generate threshold arrays to achieve blue and green noise with the computationally efficient process of ordered dither.
“Rule of Six”: How Does the Sendai Virus RNA Polymerase Keep Count? (2001)

The "rule of six" stipulates that the Paramyxovirus RNA polymerase efficiently replicates only viral genomes counting 6n + 0 nucleotides. Because the nucleocapsid proteins (N) interact with 6 nucleotides, an exact nucleotide-N match at the RNA 3'-OH end (3'-OH congruence) may be required for recognition of an active replication promoter. Alternatively, assuming that the six positions for the interaction of N with the nucleotides are not equivalent, the nucleotide position relative to N may be critical (N phase context). The replication abilities of various minireplicons, designed so that the 3'-OH congruence could be discriminated from the N phase context, were studied. The results strongly suggest that the application of the rule of six depends on the recognition of nucleotides positioned in the proper N phase context.
Living Polymerization of Carbodiimides Initiated by Copper(I) and Copper(II) Amidinate Complexes (1997)

Various catalysts for the polymerization of carbodiimide have been investigated. In early studies, anionic polymerization techniques were employed, but the products obtained were low molecular weight oligomers. More recently, a living route using titanium(IV) complexes as initiators has been employed and the high molecular weight polymers obtained exhibit a well-ordered helical, extended-chain conformation. However, the titanium complexes are sensitive to high temperatures and the presence of oxygen or water. Herein, we report that more robust catalysts based on copper(I) and copper(II) complexes also initiate living carbodiimide polymerizations. The tolerance of these complexes to impurities is illustrated by the fact that they cleanly initiate the polymerization of carbodiimides under air and oxygen. They are even active in the presence of water, but both molecular weights and yields tend to be lower than in dry solvents. It has been shown that the catalytic activity of a copper(II) amidinato complex is almost equal that of reported titanium(IV) initiators. Analysis of these systems by gel permeation chromatography−light scattering measurements (GPC−LS) and preliminary kinetic analysis suggest this system to be living.
Brain Serotonin Concentration: Elevation Following Intraperitoneal Administration of Melatonin (1968)

The intraperitoneal administration of melatonin to rats caused an increase in brain serotonin concentration, especially in the midbrain. This effect could be demonstrated within 20 minutes of melatonin administration and was not associated with changes in norepinephrine concentration.
FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases (2014)

Fibroblast growth factor (FGF) family members are mostly secreted as signaling proteins with diverse functions in development and metabolism. FGF21 is a unique FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by different kinds of stress and acts though FGF receptor 1c with β-Klotho as a cofactor in an endocrine or, in parts, autocrine/paracrine manner. Hepatic FGF21 directly acts on white adipocytes to inhibit lipolysis and acts through the brain to increase systemic glucocorticoid levels and suppress physical activity in response to starvation. It also protects against dioxin toxicity. Adipocytic FGF21 induces the browning of white adipose tissue (WAT) and activates brown adipocytes in response to cold exposure. It also acts as an upstream effector of adiponectin in white adipocytes. Myocytic FGF21 protects against diet-induced obesity and insulin resistance, induces the browning of WAT, and protects against cardiac hypertrophy. In addition, Fgf21 polymorphisms are possibly related with metabolic diseases and FGF21 are biomarker of metabolic diseases. These findings indicate that FGF21 plays roles as a hepatokine, adipokine, and myokine in metabolism, injury protection, and diseases.
Shiga Toxin Gene Loss and Transfer In Vitro and In Vivo during Enterohemorrhagic Escherichia coli O26 Infection in Humans (2007)

Escherichia coli serogroup O26 consists of enterohemorrhagic E. coli (EHEC) and atypical enteropathogenic E. coli (aEPEC). The former produces Shiga toxins (Stx), major determinants of EHEC pathogenicity, encoded by bacteriophages; the latter is Stx negative. We have isolated EHEC O26 from patient stools early in illness and aEPEC O26 from stools later in illness, and vice versa. Intrapatient EHEC and aEPEC isolates had quite similar pulsed-field gel electrophoresis (PFGE) patterns, suggesting that they might have arisen by conversion between the EHEC and aEPEC pathotypes during infection. To test this hypothesis, we asked whether EHEC O26 can lose stx genes and whether aEPEC O26 can be lysogenized with Stx-encoding phages from EHEC O26 in vitro. The stx2 loss associated with the loss of Stx2-encoding phages occurred in 10% to 14% of colonies tested. Conversely, Stx2- and, to a lesser extent, Stx1-encoding bacteriophages from EHEC O26 lysogenized aEPEC O26 isolates, converting them to EHEC strains. In the lysogens and EHEC O26 donors, Stx2-converting bacteriophages integrated in yecE or wrbA. The loss and gain of Stx-converting bacteriophages diversifies PFGE patterns; this parallels findings of similar but not identical PFGE patterns in the intrapatient EHEC and aEPEC O26 isolates. EHEC O26 and aEPEC O26 thus exist as a dynamic system whose members undergo ephemeral interconversions via loss and gain of Stx-encoding phages to yield different pathotypes. The suggested occurrence of this process in the human intestine has diagnostic, clinical, epidemiological, and evolutionary implications.
Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4 (2013)

Gram-negative bacteria including Escherichia coli, Citrobacter rodentium, Salmonella typhimurium, and Shigella flexneri are sensed in an ill-defined manner by an intracellular inflammasome complex that activates caspase-11. We show that macrophages loaded with synthetic lipid A, E. coli lipopolysaccharide (LPS), or S. typhimurium LPS activate caspase-11 independently of the LPS receptor Toll-like receptor 4 (TLR4). Consistent with lipid A triggering the noncanonical inflammasome, LPS containing a divergent lipid A structure antagonized caspase-11 activation in response to E. coli LPS or Gram-negative bacteria. Moreover, LPS-mutant E. coli failed to activate caspase-11. Tlr4(-/-) mice primed with TLR3 agonist polyinosinic:polycytidylic acid [poly(I:C)] to induce pro-caspase-11 expression were as susceptible as wild-type mice were to sepsis induced by E. coli LPS. These data unveil a TLR4-independent mechanism for innate immune recognition of LPS.
Breaking Barriers through Single Molecule, Real Time Sequencing (2010)

RP-26

This presentation is an overview of the novel applications enabled by SMRT™ sequencing. In addition to describing the performance specifications of the instrument which will ship later this year, we will give an overview of useful characteristics of the system: long readlength, fast time-to-result, high accuracy through circular consensus, robust immunity from systematic error and sequence content bias, and richer data. These features will then be highlighted through application to model systems. Transcript sequencing has previously been limited to messages less than ~1100 bases in length for sequencing in one contiguous read. We will present a >3,000-base transcript sequenced in a single read, encompassing an entire aberrant cancer transcript. We will apply strobe sequencing — a method to further extend the physical coverage of individual reads — to structural variations in complex genomes demonstrating individual reads to10,000 bases. The fast time-to-data will be exploited in a study of H1N1 influenza virus in which we traverse the entire process from sample arrival to variant identification in less than 10 hours. We will show a completed sequence of a GC-rich organism relevant to biofuel generation enabled by our long read technology. We will show how the rich set of kinetic information allows direct detection of various forms of modified bases such as 5-methylcytosine, 5-hydroxymethyl cytosine, N6 methyladenosine as well as a host of other medically and biologically important modifications. We will culminate by demonstrating applications of the SMRT detection system to follow SMRT DNA sequencing. First, we will show sequencing of RNA directly in real time without conversion to cDNA through the use of an RNA-templating polymerase, and second we will show the first real-time detection of translation with amino acid resolution by a ribosome immobilized in a ZMW.
Fructose 2,6‐bisphosphate and the control of glycolysis in bovine spermatozoa (1986)

Epididymal bovine sperm contain fructose-1,6-bisphosphatase activity which is inhibited by AMP and by fructose 2,6-bisphosphate. Sperm phosphofructokinase displays kinetic characteristics that are typical of the F-type and it is stimulated by fructose 2,6-bisphosphate. The concentration of sperm fructose 2,6-bisphosphate remained unaffected at 1-2 microM when the glycolytic rate was either increased by glucose, caffeine or antimycin, or decreased by alpha-chlorohydrin or 6-chloro-6-deoxyglucose.
Production of Ascaris suum As14 Protein and Its Fusion Protein with Cholera Toxin B Subunit in Rice Seeds (2009)

Plants are attractive vaccine production and oral delivery systems. Cereals are excellent candidate for edible vaccines, which can express and store high levels of proteins for extended periods of time without degradation. In this study, we produced a 14-kDa protective surface antigen of Ascaris suum L3 larvae and its fusion chimera with a mucosal carrier molecule cholera toxin B subunit (CTB) in rice (Oryza sativa L.) under the control of the endosperm-specific glutelin-B promoter. We found that the recombinant protein expression levels reached 1.5 microg per seed, a comparably high amount as compared to previously reported transgenic rice expression experiments. Potentials of transgenic rice plants as a source of oral vaccines against swine roundworm are discussed.
MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia (2007)

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, whereas acute myeloid leukemia (AML) is the most common acute leukemia in adults. In general, ALL has a better prognosis than AML. To understand the distinct mechanisms in leukemogenesis between ALL and AML and to identify markers for diagnosis and treatment, we performed a large-scale genome-wide microRNA (miRNA, miR) expression profiling assay and identified 27 miRNAs that are differentially expressed between ALL and AML. Among them, miR-128a and -128b are significantly overexpressed, whereas let-7b and miR-223 are significantly down-regulated in ALL compared with AML. They are the most discriminatory miRNAs between ALL and AML. Using the expression signatures of a minimum of two of these miRNAs resulted in an accuracy rate of >95% in the diagnosis of ALL and AML. The differential expression patterns of these four miRNAs were validated further through large-scale real-time PCR on 98 acute leukemia samples covering most of the common cytogenetic subtypes, along with 10 normal control samples. Furthermore, we found that overexpression of miR-128 in ALL was at least partly associated with promoter hypomethylation and not with an amplification of its genomic locus. Taken together, we showed that expression signatures of as few as two miRNAs could accurately discriminate ALL from AML, and that epigenetic regulation might play an important role in the regulation of expression of miRNAs in acute leukemias.
Antibody-induced modulation and intracellular transport of CD10 and CD19 antigens in human B-cell lines: an immunofluorescence and immunoelectron microscopy study (1993)

Antibody-induced antigenic modulation (AIAM) of CD10 and CD19 was studied on NALM-6, RAJI, and JOK-1 cell lines using fluorescence microscopy (FM), flow cytometry (FCM), and immunoelectron microscopy (IEM). Cross-linking with monoclonal antibodies (MoAbs) induced rapid redistribution of CD10 and CD19 on the cell surface (FM) followed by internalization involving uptake through plasmalemmal pits, transfer through endosomal compartment (receptor-mediated endocytosis), and, finally, delivery to lysosomes for degradation or exocytosis and recycling (IEM). Significant quantitative differences regarding modulation and intracellular processing were shown by FCM and IEM. Thus, 35%, 30%, and 25% of CD10 compared with 80%, 60%, and 40% of CD19 were internalized in NALM-6, RAJI, and JOK-1 cells, respectively. Also, the rate of intracellular transfer as well as externalization and recycling was more pronounced in the case of CD19 than of CD10 and in the NALM-6 and RAJI cells compared with the JOK-1 cells. These differences may possibly reflect the functional significance of CD10 and CD19 as well as the stage of differentiation of the malignant B cells. Although both antigens can be useful in MoAb-targeted immunotherapy, our findings suggest that anti-CD19 MoAbs would be preferable for delivery of cytotoxic agents to malignant B cells.
Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression (2020)

While most monogenic diseases are caused by loss or reduction of protein function, the need for technologies that can selectively increase levels of protein in native tissues remains. Here we demonstrate that antisense-mediated modulation of pre-mRNA splicing can increase endogenous expression of full-length protein by preventing naturally occurring non-productive alternative splicing and promoting generation of productive mRNA. Bioinformatics analysis of RNA sequencing data identifies non-productive splicing events in 7,757 protein-coding human genes, of which 1,246 are disease-associated. Antisense oligonucleotides targeting multiple types of non-productive splicing events lead to increases in productive mRNA and protein in a dose-dependent manner in vitro. Moreover, intracerebroventricular injection of two antisense oligonucleotides in wild-type mice leads to a dose-dependent increase in productive mRNA and protein in the brain. The targeting of natural non-productive alternative splicing to upregulate expression from wild-type or hypomorphic alleles provides a unique approach to treating genetic diseases.