gebhart/patrepeval huggingface dataset:
Rheological Properties of Vaginal Hydrophilic Polymer Gels (2009)

The objective of this work was to investigate the main theological features of vaginal hydrophilic polymer gels and to elucidate about the relationship between these characteristics and gels composition, and their general influence in therapeutic/usage purpose. Flow and dynamic oscillatory properties of four commercially available (Conceptrol, Gynol II, RepHresh, and Replens) and two investigational vaginal gels were determined by cone-and-plate rheometry, at body temperature. Several parameters (apparent viscosity, complex viscosity, storage modulus, loss modulus, critical oscillatory stress, tan delta, thixotropy and yield stress) were measured and/or calculated. Gels presented non-Newtonian, pseudoplastic, thixotropic behavior, with yield stress. Overall viscosities varied between 13500 Pa.s and approximately 80 Pa.s within a biologically relevant shear rate interval (0.01-100 s(-1)). Yield stress values were variable between different determination methods but coherent in terms of ranking. Also, tested gels showed viscoelastic properties, being characterized by predominant elastic solid-like behavior. Rheological behavior of vaginal gels strongly depended on the type of gelling agent used, which potentially influences their spreading and retention properties when administered in the vaginal canal. Small variations in gels composition can result in substantial changes in their features, namely viscosity, yield stress and thixotropy. Rheological properties of tested gels appeared to be correlated with their therapeutic/usage purpose.
Hand Rehabilitation Following Stroke: A Pilot Study of Assisted Finger Extension Training in a Virtual Environment (2007)

After the training period, participants in all 3 groups demonstrated a decrease in time to perform some of the functional tasks. Although the overall gains were slight, the general acceptance of the novel rehabilitation tools by a population with substantial impairment suggests that a larger randomized controlled trial, potentially in a subacute population, may be warranted.
Abstract P6-13-02: A phase 1 dose escalation study of RAD1901, an oral selective estrogen receptor degrader, in healthy postmenopausal women (2016)

Abstract Estrogen and the estrogen receptor (ER) are known to be prominent drivers of breast tumourigenesis and breast cancer progression. Hormonal agents that target the ER such as selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) are routinely used for the management for ER+ breast cancer. Fulvestrant is currently the only SERD approved for the treatment of ER-positive metastatic breast cancer, however, despite its clinical efficacy, the utility of fulvestrant has been limited by the amount of drug that can be administered in a single injection, the reduced bioavailability and the development of resistance in some patients. To overcome some of the challenges associated with current endocrine therapies there is a need for more durable and more effective ER-targeted therapies. RAD1901 is a novel, non-steroidal, orally bioavailable SERD. Preclinical studies demonstrated a favorable tissue selectivity profile, dose dependent ER degradation and potent inhibition of in vitro breast cancer cell proliferation. Significant tumor regression was consistently observed with RAD1901 treatment, compared to Tamoxifen or Fulvestrant in MCF7 and patient derived xenograft models, including those harboring ESR1 mutations. Here we describe a Phase 1 clinical study that was conducted in 52 healthy postmenopausal female volunteers. Cohorts of 10 subjects (2 placebo, 8 RAD1901 treated) were dosed with 200 mg, 500 mg, 750 mg or 1000 mg for 7 days. Additional subjects were enrolled to an 18F-estradiol positron emission tomography (FES-PET) cohort to evaluate the 200 mg (n=7 subjects) and 500 mg (n=6 subjects) dose levels. All dose levels were generally well tolerated with a total of 43/52 subjects completing the study. Pharmacokinetic analysis demonstrated good plasma exposure with dose proportional increases. FES-PET was performed at baseline and after 7 days of treatment with RAD1901, to assess estrogen receptor engagement. Standardized uptake values (SUV) pre- and post-treatment demonstrated a complete attenuation of FES-PET signal in ER-rich tissues such as the uterus at the 500 mg/day dose level, whereas almost 80% reduction in the signal was observed at the 200 mg/day dose level. Based on these preclinical and clinical results, RAD1901 is currently being investigated in a Phase 1 study for the treatment of hormone driven and hormone resistant metastatic breast cancers. Citation Format: Hattersley G, David F, Harris A, Clarkin M, Banks K, Glaudemans AWJM, Doorduin J, Koole M, de Vries EFJ, Williams G. A phase 1 dose escalation study of RAD1901, an oral selective estrogen receptor degrader, in healthy postmenopausal women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-13-02.
Ultrasound Diagnosis of Craniosynostosis (2002)

No diagnosis of craniosynostosis was made in the first trimester. In the second trimester, it was possible to diagnose Kleeblattschädel, trigonocephaly, brachycephaly (bilateral coronal suture craniosynostosis), and plagiocephaly (unilateral coronal suture craniosynostosis) in nine of the examinations. In the third trimester and at term, it was possible to diagnose previously listed conditions from six of the seven examinations obtained. Kleeblattschädel was suspected during original examination. A total of 15 examinations of 26 were correctly diagnosed during this investigation.
Pharmacokinetics of liposome encapsulated cisplatin in rats. (1982)

The chemotherapeutic anticancer agent Cisplatin--cis-diamine-dichloroplatinum (II)--has several disadvantages, such as its extreme nephrotoxicity, fast elimination via the kidneys, and rapid binding to plasma proteins. Encapsulation into negatively charged, multilamellar liposomes (MLV), composed of egg-lecithin: cholesterol: dicetylphosphate in 5:5:1 molar ratio, causes drastic changes in behavior after a single i.v. injection: marked increase in the circulation half life paralleled by slower urinary excretion; remarkedly higher levels of free drug in the blood; increased uptake in liver, spleen and lymph nodes, and decreased uptake in skin and bones. In the kidneys a reduced and retarded uptake over 15 hr, then a higher uptake was found. The liposomal Cisplatin has a strong transitory diuretic effect, which nevertheless is not paralleled by other signs of renal injury such as decreased output of creatinine or increased output of protein or urinary enzymes. By pre-ejection of empty liposomes the diuresis can be reduced and the additional Pt deposit in the kidneys prevented.
An advanced English grammar, with exercises (1913)

Book digitized by Google from the library of Harvard University and uploaded to the Internet Archive by user tpb.
Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells (2014)

A proper balance between Th17 and T regulatory cells (Treg cells) is critical for generating protective immune responses while minimizing autoimmunity. We show that the Tec family kinase Itk (IL2-inducible T cell kinase), a component of T cell receptor (TCR) signaling pathways, influences this balance by regulating cross talk between TCR and cytokine signaling. Under both Th17 and Treg cell differentiation conditions, Itk(-/-) CD4(+) T cells develop higher percentages of functional FoxP3(+) cells, associated with increased sensitivity to IL-2. Itk(-/-) CD4(+) T cells also preferentially develop into Treg cells in vivo. We find that Itk-deficient T cells exhibit reduced TCR-induced phosphorylation of mammalian target of rapamycin (mTOR) targets, accompanied by downstream metabolic alterations. Surprisingly, Itk(-/-) cells also exhibit reduced IL-2-induced mTOR activation, despite increased STAT5 phosphorylation. We demonstrate that in wild-type CD4(+) T cells, TCR stimulation leads to a dose-dependent repression of Pten. However, at low TCR stimulation or in the absence of Itk, Pten is not effectively repressed, thereby uncoupling STAT5 phosphorylation and phosphoinositide-3-kinase (PI3K) pathways. Moreover, Itk-deficient CD4(+) T cells show impaired TCR-mediated induction of Myc and miR-19b, known repressors of Pten. Our results demonstrate that Itk helps orchestrate positive feedback loops integrating multiple T cell signaling pathways, suggesting Itk as a potential target for altering the balance between Th17 and Treg cells.
Compact Sources of Ultrashort Pulses (2006)

This comprehensive volume provides a survey of the many innovations in the field of ultrashort pulse generation, and reviews the state of the art in compact, modelocked laser systems, discussing both their operational principles and potential applications. The theory of short optical pulse generation by modelocking is covered in the first chapter. Thereafter, modelocking techniques in different types of lasers are discussed: solid state lasers; diode-pumped lasers; fiber lasers; surface emitting semiconductor lasers; external cavity semiconductor lasers; hybrid soliton pulse sources; and monolithic colliding pulse modelocked diode lasers. Presenting both theoretical and experimental aspects throughout, this book will be invaluable to anyone interested in short pulse laser systems, and particularly to researchers involved in high-speed communications or the investigation of ultrafast phenomena
H7N9 avian flu infects humans for the first time (2013)

The H7N9 avian influenza virus has infected humans for the first time, killing three people in China—two in Shanghai in March, and one in Hangzhou whose death was reported on 3 April. It is known to have infected a further six people in different locations across the Yangtze delta region of eastern China, all of whom are in a critical condition in hospital.

Fadela Chaib, spokesperson for the World Health Organization, said at a press conference in Geneva, “It’s the first time that H7N9 has been found in humans, so it’s of concern to WHO,” adding that, although it would be asking the health authorities in China for an update, for the time being the virus has not shown any human to human transmission.

The two deaths in Shanghai …
Tranexamic acid is an active site inhibitor of urokinase plasminogen activator (2019)

Key Points TXA is an active-site inhibitor of uPA. TXA attenuates MDA-MB-231 BAG cell migration and inhibits endogenous uPA activity.
The Politics of Memory: Nation, Individual and Self (1999)

The Japanese political world has splintered to pieces in the aftermath of the cold war. The same splintering has occurred among intellectuals as well, as one distorted claim invites another, until one hasn't a clue who is conservative and who is progressive. The present focus of the confusion is the so-called comfort women problem. Holocaust revisionism has created scandals in the past in Japan as elsewhere, but this time the fire has ignited on our own doorstep. With the emergence of a Japanese version of historical revisionism, the comfort women issue has become a litmus test of attitudes about war responsibility and the construction of public memory.
Growth-Associated Expression of a Membrane Protein, Neuropilin, in <i>Xenopus </i>Optic NerveFibers (1995)

Neuropilin (previously referred to as A5) is a neuronal cell surface protein which is widely distributed in such vertebrate species as Xenopus, chicken and mouse. In these vertebrate species, neuropilin is expressed in particular neuron circuits at particular developmental stages when axonal growth is active. To test whether the expression patterns of neuropilin is associated with axonal growth, we examined expression patterns of neuropilin in developing and regenerating Xenopus optic nerves. In embryos, a neuropilin-specific monoclonal antibody A5 (MAbA5) bound strongly to the optic nerves, and in situ hybridization signals for neuropilin mRNA were prominent in the retinal ganglion cells (RGCs), indicating that developing optic nerve fibers express neuropilin. The binding of MAbA5 to the optic nerve fibers was maximal at stages 41-43, then decreased in the subsequent tadpole life. In tadpoles after stage 50, the binding of MAbA5 to the optic nerves was extremely weak or almost nil, although RGCs expressed considerable amounts of neuropilin mRNA. When the tadpole optic nerves were crushed and prompted to regenerate, however, neuropilin protein reappeared in the optic nerve fibers. The binding of MAbA5 to the regenerating optic nerve fibers was detectable as early as the 5th day and maximal at the 2nd or 3rd weeks after the optic nerve crush, and declined thereafter. These findings suggest that the expression of neuropilin in the optic nerve fibers is regulated in an axonal growth-associated manner.
Chromosome 17q12 Variants Contribute to Risk of Early-Onset Prostate Cancer (2008)

In a recent genome-wide association study by Gudmundsson and colleagues, two prostate cancer susceptibility loci were identified on chromosome 17q. The first locus, at 17q12, was distinguished by two intronic single-nucleotide polymorphisms (SNPs) in the TCF2 gene (rs4430796 and rs7501939). The second locus was in a gene-poor region of 17q24, where the strongest evidence of association was for SNP rs1859962. To determine if these loci were also associated with hereditary prostate cancer, we genotyped them in a family-based association sample of 403 non-Hispanic white families, including 1,015 men with and without prostate cancer. SNPs rs4430796 and rs7501939, which were in strong linkage disequilibrium (r(2) = 0.68), showed the strongest evidence of prostate cancer association. Using a family-based association test, the A allele of SNP rs4430796 was overtransmitted to affected men (P = 0.006), with an odds ratio of 1.40 (95% confidence interval, 1.09-1.81) under an additive genetic model. Notably, rs4430796 was significantly associated with prostate cancer among men diagnosed at an early (<50 years) but not later age (P = 0.006 versus P = 0.118). Our results confirm the prostate cancer association with SNPs on chromosome 17q12 initially reported by Gudmundsson and colleagues. In addition, our results suggest that the increased risk associated with these SNPs is approximately doubled in individuals predisposed to develop early-onset disease. Importantly, these SNPs do not account for a significant portion of our prior prostate cancer linkage evidence on chromosome 17. Thus, there likely exist one or more additional independent prostate cancer susceptibility loci in this region.
Establishment of FUT8 knockout Chinese hamster ovary cells: An ideal host cell line for producing completely defucosylated antibodies with enhanced antibody‐dependent cellular cytotoxicity (2004)

To generate industrially applicable new host cell lines for antibody production with optimizing antibody-dependent cellular cytotoxicity (ADCC) we disrupted both FUT8 alleles in a Chinese hamster ovary (CHO)/DG44 cell line by sequential homologous recombination. FUT8 encodes an alpha-1,6-fucosyltransferase that catalyzes the transfer of fucose from GDP-fucose to N-acetylglucosamine (GlcNAc) in an alpha-1,6 linkage. FUT8(-/-) cell lines have morphology and growth kinetics similar to those of the parent, and produce completely defucosylated recombinant antibodies. FUT8(-/-)-produced chimeric anti-CD20 IgG1 shows the same level of antigen-binding activity and complement-dependent cytotoxicity (CDC) as the FUT8(+/+)-produced, comparable antibody, Rituxan. In contrast, FUT8(-/-)-produced anti-CD20 IgG1 strongly binds to human Fcgamma-receptor IIIa (FcgammaRIIIa) and dramatically enhances ADCC to approximately 100-fold that of Rituxan. Our results demonstrate that FUT8(-/-) cells are ideal host cell lines to stably produce completely defucosylated high-ADCC antibodies with fixed quality and efficacy for therapeutic use.
New catalysts and procedures for the dimethoxytritylation and selective silylation of ribonucleosides (1982)

Procedures have been developed for the selective formation of (a) 2′,5′-silylated ribonucleosides and (b) 3′,5′-silylated ribonucleosides. These procedures also permit the selective silylation at either the 2′- or 3′-position of dimethoxytritylated ribonucleosides. The procedures involve nitrate or perchlorate ion catalysis for selective reaction at 2′-positions and a combination of silver ion and DABCO or 4-nitropyridine N-oxide for selective reaction at the 3′-position. During the course of this work a general and rapid procedure was developed for the preparation and isolation of the 5′-dimethoxytrityl derivatives of the four common ribonucleosides. Silver ion was found to have a marked effect on dimethoxytritylation reactions.
Transplants of immunologically isolated xenogeneic chromaffin cells provide a long-term source of pain-reducing neuroactive substances (1993)

Adrenal medullary chromaffin cells are a potential source of neuroactive substances for transplantation into the CNS to alleviate neurochemical deficits. In particular, work in our laboratory has suggested that adrenal medullary transplants in the spinal subarachnoid space can alleviate pain by providing sustained local delivery of catecholamines and opioid peptides. One of the major limitations for clinical application of neural transplantation is the availability of donor material in sufficient quantities. This limitation may be overcome by the use of xenogeneic donors if long-term graft rejection can be prevented. The purpose of this study was to assess whether xenogeneic chromaffin cells immunologically isolated by semipermeable membranes could survive and continue to reduce pain when transplanted into the CNS. Isolated bovine chromaffin cells were encapsulated by semipermeable polymer membranes and implanted into the rat spinal subarachnoid space. Pain sensitivity was assessed at several intervals up to 3 months following implantation. Results indicated that encapsulated bovine chromaffin cell implants, but not empty control capsules, could repeatedly reduce pain sensitivity with nicotine stimulation for the duration of the study. This response was dose related, indicating that pharmacologic integrity of the transplanted chromaffin cells is retained. The analgesia induced by encapsulated chromaffin cell implants could be attenuated by the opiate antagonist naloxone and the alpha-adrenergic antagonist phentolamine, suggesting the involvement of both opioid peptides and catecholamines in mediating this response. In addition, in vitro neurochemical studies of recultured capsules revealed sustained release of Met-enkephalin and catecholamines from encapsulated cells 3 months following implantation into the spinal subarachnoid space.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression (2006)

The plant-derived cannabinoids delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both have immunosuppressive effects; although some effects of THC are mediated by the CB2 receptor, CB2 binds CBD weakly. In examining the effects of THC and CBD on microglial proliferation, we found that these compounds potently inhibit [3H]thymidine incorporation into a murine microglial cell line with no effect on cell cycle. Treatment with THC and CBD decreased [3H]thymidine uptake into microglia, with IC50 values that match inhibition of [3H]thymidine incorporation into DNA. CBD and, less potently, THC decreased uptake of [3H]adenosine to a similar extent as [3H]thymidine in both murine microglia and RAW264.7 macrophages. Binding studies confirm that CBD binds to the equilibrative nucleoside transporter 1 with a Ki < 250 nM. Because adenosine agonists have antiinflammatory effects, and because uptake of adenosine is a primary mechanism of terminating adenosine signaling, we tested the hypothesis that CBD is immunosuppressive because it enhances endogenous adenosine signaling. In vivo treatment with a low dose of CBD decreases TNFalpha production in lipopolysaccharide-treated mice; this effect is reversed with an A2A adenosine receptor antagonist and abolished in A2A receptor knockout mice. These studies demonstrate that CBD has the ability to enhance adenosine signaling through inhibition of uptake and provide a non-cannabinoid receptor mechanism by which CBD can decrease inflammation.
High‐resolution assessment of blood flow in murine RIF‐1 tumors by monitoring uptake of H217O with proton T1ρ‐weighted imaging (2002)

Perfusion parameters, such as blood flow, are critical properties of tumors related to angiogenesis, drug delivery, radiosensitivity, bioenergetic status, and steady state levels of metabolites, such as lactate, that have been proposed as indices of tumor response to therapy. The existing MR methods for measuring tumor blood flow (TBF) have limitations related to sensitivity, spatial resolution, or dependence on other physiological properties such as vascular permeability. To address many of these difficulties, this study introduces the use of an (17)O-enriched tracer in conjunction with high-resolution, indirect MRI to measure TBF. To demonstrate the advantages of this technique, relative TBF was measured in subcutaneous RIF-1 tumors in C3H mice by monitoring the uptake of H(2) (17)O with a resolution of 0.16 x 0.31 x 3 mm in 13 sec. At this resolution, tumor heterogeneity with respect to blood flow is clearly visible. Measurement of the tracer arterial input function, which is necessary for determination of absolute blood flow, may be facilitated with improved temporal resolution.
A Modular High Density Multi-Channel Dispenser for Micro-Array Printing (2003)

A multi-channel dispenser for micro-array printing has been developed and characterized. We report the fabrication of the dispenser using flexible Polyimide substrate. Polyimide sheets have been dry etched to form /spl mu/-channels. These sheets are sealed with virgin Polyimide sheets by a thermal bonding process. Piezoelectric actuators have been glued onto the channels. 1-dimensional dispenser array has been stacked together to form a 2-dimensional printing array at a nozzle spacing of 500 /spl mu/m. The actuator displacement has been investigated by finite element analysis and by measurements during dispensing for different electrical pulse shapes. The drop formation is recorded with a standard video camera with stroboscope illumination. Droplets of 65 pL have been ejected in parallel at a speed of 2-3 m/s and up to a frequency of 5 KHz.
Human single-chain Fv (scFv) antibody specific to human IL-6 with the inhibitory activity on IL-6-signaling (2003)

Human anti-IL-6 antibody may be useful for the immunotherapy of various inflammatory diseases, such as rheumatoid arthritis. Since IL-6 is a growth factor for B cell hybridoma, it is not easy to isolate murine B cell hybridomas producing the anti-IL-6 antibody with the IL-6-signaling inhibitory activity. In this study, the antibody library (Vgamma-Vkappa, Vgamma-Vlambda, Vmu-Vkappa or micro-Vlambda ligated into the pCANTAB 5E phagemid vector) was prepared from peripheral blood mononuclear cells of 20 healthy subjects. The phage display library was panned with an IL-6-coated plastic plate, and the binding specificity was confirmed by ELISA and BIAcore. From the antibody library (Vgamma-Vlambda), five IL-6-specific phage clones were isolated. The effects of the soluble scFvs purified from these phage clones were tested on the growth of the IL-6-dependent human cell line, KT-3. Two of these clones significantly inhibited the growth of KT-3, and three showed no inhibition.