gebhart/patrepeval huggingface dataset:
Oral low dose and topical tamoxifen for breast cancer prevention: modern approaches for an old drug (2012)

Tamoxifen is a drug that has been in worldwide use for the treatment of estrogen receptor (ER)-positive breast cancer for over 30 years; it has been used in both the metastatic and adjuvant settings. Tamoxifen's approval for breast cancer risk reduction dates back to 1998, after results from the Breast Cancer Prevention Trial, co-sponsored by the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project, showed a 49% reduction in the incidence of invasive, ER-positive breast cancer in high-risk women. Despite these positive findings, however, the public's attitude toward breast cancer chemoprevention remains ambivalent, and the toxicities associated with tamoxifen, particularly endometrial cancer and thromboembolic events, have hampered the drug's uptake by high-risk women who should benefit from its preventive effects. Among the strategies to overcome such obstacles to preventive tamoxifen, two novel and potentially safer modes of delivery of this agent are discussed in this paper. Low-dose tamoxifen, expected to confer fewer adverse events, is being investigated in both clinical biomarker-based trials and observational studies. A series of systemic biomarkers (including lipid and insulin-like growth factor levels) and tissue biomarkers (including Ki-67) are known to be favorably affected by conventional tamoxifen dosing and have been shown to be modulated in a direction consistent with a putative anti-cancer effect. These findings suggest possible beneficial clinical preventive effects by low-dose tamoxifen regimens and they are supported by observational studies. An alternative approach is topical administration of active tamoxifen metabolites directly onto the breast, the site where the cancer is to be prevented. Avoidance of systemic administration is expected to reduce the distribution of drug to tissues susceptible to tamoxifen-induced toxicity. Clinical trials of topical tamoxifen with biological endpoints are still ongoing whereas pharmacokinetic studies have already shown that appropriate formulations of drug successfully penetrate the skin to reach breast tissue, where a preventive effect is sought.
Cow's Milk Whey Protein Elicits Symptoms of Infantile Colic in Colicky Formula-Fed Infants: A Double-Blind Crossover Study (1989)

There are several causes of infantile colic. The aim of this study was to evaluate, under controlled conditions, whether bovine whey proteins can elicit symptoms of infantile colic in colicky formula-fed infants. The mean age for entering the study was 6.4 weeks and the mean age for colic debut was 3.7 weeks. In 24 of 27 infants with severe colic, the symptoms disappeared when they were given a cow's milk-free diet (Nutramigen). These 24 infants were entered into a double-blind crossover study. The infants (receiving cow's milk-free diet) were given the contents of identical capsules with each meal during day 6. The same procedure was repeated on day 10. The capsules contained either whey protein powder (with Nutramigen added) or human albumin powder (with Nutramigen added). Eighteen infants receiving the whey protein-containing capsules reacted with colic, two infants receiving placebo reacted with colic (P less than .001), and four infants did not react at all. Crying hours per day for the 24 infants were 5.6 hours for formula-fed infants and 0.7 hour for cow's milk-free diet-fed infants (P less than .001). Crying hours per day were 3.2 hours for the infants receiving whey protein capsules and 1.0 hour for those receiving placebo (P less than .001). In conclusion, bovine whey protein can elicit symptoms of infantile colic in colicky formula-fed infants.
Cambodia and the ASEAN Economic Community: Opportunities, Challenges, and Implications for Human Resource Development (2014)

The purpose of this paper is to examine the opportunities, challenges, and implications for human resource development (HRD) for Cambodia in joining the Association of Southeast Asian Nations (ASEAN) Economic Community in 2015. The paper starts by providing an overview of ASEAN as a regional institution and the rationale for the ASEAN Economic Community (AEC) 2015. The second section outlines and discusses current HRD practices in Cambodia, which include the country's National Strategic Development Plan and Rectangular Strategy, higher education system, vocational and technical education system, and HRD through the private sector. What follows is an in-depth analysis of the main HRD challenges facing Cambodia, namely ASEAN integration challenges, mismatches between education and employment, problems with higher education and technical and vocational education systems, challenges in technology development and HRD, and a lack of awareness and engagement in the AEC processes. The paper concludes by discussing the implications for research and practices as regards Cambodia's integration in the ASEAN Economic Community.
Diagnosis and management of idiopathic normal-pressure hydrocephalus: a prospective study in 151 patients (2005)

Data in this report affirm that gait improvement immediately following ELD is the best prognostic indicator of a positive shunt outcome, with an accuracy of prediction greater than 90%. Furthermore, bolus resistance testing is useful as a prognostic tool, does not require hospitalization, can be performed in an outpatient setting, and has an overall accuracy of 72% in predicting successful ELD outcome. Equally important is the finding that improvement with shunt surgery is independent of age up to the ninth decade of life in patients who improved on ELD.
Improved Detection of Anti‐HCV in Post‐Transfusion Hepatitis by a Third‐Generation ELISA (1995)

The sensitivity of ORTHO HCV 3.0 ELISA Test System (ELISA 3) for the detection of anti-HCV was compared with the second-generation ELISA, OR-THO HCV 2.0 ELISA Test System (ELISA 2). ELISA 3 differs from ELISA 2 in that it incorporates the HCV recombinant antigen NS5, in addition to recombinant antigens derived from the NS3, NS4 and core regions of the HCV genome. Specimens tested consisted of serial bleeds obtained from 21 individuals undergoing seroconversion following acquisition of post-transfusion HCV infection. ELISA 3 demonstrated significantly greater sensitivity than ELISA 2, detecting seroconversion earlier in 24% (5/21) of cases. Although one of these cases appeared to represent early seroconversion to NS5, most of the improved sensitivity of ELISA 3 appeared to derive from increased detectability of anti-c33c.
The synthesis of 10-(4-methylpiperazino)dibenzo(b,f)thiepin and related compounds. Neurotropic and psychotropic agents. (1975)

The preparation of 10-(4-methylpiperazino) dibenzo [b, f] thiepin (16a) and related Compounds is described. The reduction of 16a in an acidic medium yield the dihydro derivative (21) which was pharmacologically a valuable compound. Many of the compounds in this series showed marked neuroleptic effects similary to octoclotepine (2).
A phase 1a clinical trial of LYM‐1 monoclonal antibody serotherapy in patients with refractory b cell malignancies (1989)

Ten patients with refractory B cell lymphomas were treated with weekly intravenous infusions of escalating doses of murine monoclonal antibody (MoAb) LYM-1 over four weeks. LYM-1 is a recently developed IgG2a murine MoAb that recognizes a polymorphic HLA-Dr antigen on surfaces of normal and malignant B cells but does not bind to any other normal tissues. MoAb LYM-1 has several advantages for serotherapy, since the antigen it recognizes is not shed from the cell surface and does not modulate in response to MoAb therapy. Furthermore, in vitro studies have indicated significant anti-tumour activity against lymphoma cell lines. In the current trial, dose-dependent levels of free LYM-1 were detected in the serum of all patients, but penetration of extravascular tumour tissues was poor. No significant toxicity or human anti-mouse antibody responses were observed in any patient. Clinical responses were minor and appeared to correlate with the number of infiltrating T cells seen in the initial lymphoma specimens. LYM-1 appears to be well-tolerated and has demonstrated several potential advantages as a therapeutic agent in patients with lymphoma. The mechanism of anti-tumour effect and plans for further clinical studies are discussed.
Origins of anomalous mixed-alkali effects in ion-exchanged glasses (2000)

Ion transport properties in ion-exchanged glasses are re-examined by a.c. impedance and infrared spectroscopies. In typical soda - lime-silica (float) glass it is shown that when Na+ ions are replaced by K+ ions, the region of highest resistivity resides in the surface, confirming the earlier result of Tomandl and Schaeffer. The existence of this anomalous impedance is correlated with cationinduced relaxations of the network (CIRON). This process enables the glass to accommodate larger ions at the expense of empty Κ sites (which in melt-grown glasses provide the stepping stones for ion migration). As a consequence of the structural relaxations, the compressive stresses stored within the surface of the glass may be smaller than expected, even when ion exchange occurs far below Tg and the effects of viscous flow can be neglected.
A 250-MHz 5-W PowerPC microprocessor with on-chip L2 cache controller (1997)

This RISC microprocessor is a new, high-performance, PowerPC microprocessor designed specifically for the mobile and high volume desktop personal computer markets. It is an advanced superscalar design with six execution units, aggressive upstream branch processing, out-of-order instruction execution, and a tightly integrated "backside" L2 cache. This dual-issue engine has a four-stage pipeline with dual 32-kB eight-way set-associative L1 caches and an integrated L2 controller with on-chip L2 tag supporting up to 1 MB of external SRAM. A thermal assist unit and an instruction cache throttling mechanism are included for thermal management in mobile applications. A 60X system bus and L2 interface speeds of 100 and 250 MHz are achieved, respectively. This microprocessor achieves workstation class performance (estimated 10 SPECint95 and 9 SPECfp95) while only dissipating 5 W at 250 MHz. The 6.35-million transistor 66.5-mm/sup 2/ die is fabricated in a 2.5-V, 0.3-/spl mu/m, five-layer metal CMOS process.
Enrichment of Cysteine-Containing Peptides from Tryptic Digests Using a Quaternary Amine Tag (2004)

A new strategy for specifically targeting cysteine-containing peptides in a tryptic digest is described. The method is based on quantitatively derivatizing cysteine residues with a quaternary amine tag (QAT). Tags were introduced into proteins following reduction of disulfide bonds through derivatization of cysteine residues with (3-acrylamidopropyl)trimethylammonium chloride. After trypsin digestion, derivatized cysteine-containing peptides were enriched by strong cation exchange chromatography. The method was validated using model peptides and a protein. The QAT strategy has several advantages over other methods for the selection of cysteine-containing peptides. One is that it increases the ionization efficiency of cysteine-containing peptides. The other is that chromatographic selection is achieved with simple, robust cation exchange chromatography columns. As a result, this new strategy provides a simple way to facilitate enrichment of cysteine-containing peptides, thereby reducing sample complexity in bottom-up proteomics.
Design of a genetic immunotoxin to eliminate toxin immunogenicity. (1995)

Host antibody response to toxin molecules is a major obstacle to the use of immunotoxins as efficacious agents in the treatment of human cancer and other diseases. In this study, a genetic form of immunotoxin has been designed which should eliminate toxin immunogenicity by replacing the toxin protein moiety with weakly immunogenic or nonimmunogenic plasmid DNA. A recombinant bifunctional fusion protein, which consists of a human antibody Fab targeting moiety [directed against gp120, the envelope glycoprotein of human immunodeficiency virus (HIV)-1] and a human DNA binding moiety (protamine), is used as a gene carrier. Toxin plasmid DNAs expressing the catalytic fragment of Pseudomonas exotoxin A (PEA) statically interact with the fusion proteins to form soluble protein-DNA complexes. The complexes are specifically transferred into HIV-1-infected cells by receptor-mediated endocytosis, resulting in selective killing of the target cells. These 'genetic immunotoxins' may have significant advantages over protein immunotoxins for the treatment of a variety of human diseases.
Binding of Sulfonylurea by AtMRP5, an Arabidopsis Multidrug Resistance-Related Protein That Functions in Salt Tolerance (2004)

Recently, a new member of the ABC transporter superfamily of Arabidopsis, AtMRP5, was identified and characterized. In the present work, we found that AtMRP5 can bind specifically to sulfonurea when it is expressed in HEK293 cells. We also present evidence for a new role of AtMRP5 in the salt stress response of Arabidopsis. We used reverse genetics to identify an Arabidopsis mutant (atmrp5-2) in which the AtMRP5 gene was disrupted by transferred DNA insertion. In root-bending assays using Murashige and Skoog medium supplemented with 100 mm NaCl, root growth of atmrp5-2 was substantially inhibited in contrast to the almost normal growth of wild-type seedlings. This hypersensitive response of the atmrp5-2 mutant was not observed during mannitol treatment. The root growth of the wild-type plant grown in Murashige and Skoog medium supplemented with the MRP inhibitor glibenclamide and NaCl was inhibited to a very similar extent as the root growth of atmrp5-2 grown in NaCl alone. The Na(+)-dependent reduction of root growth of the wild-type plant in the presence of glibenclamide was partially restored by diazoxide, a known K+ channel opener that reverses the inhibitory effects of sulfonylureas in animal cells. Moreover, the atmrp5-2 mutant was defective in 86Rb+ uptake. When seedlings were treated with 100 mm NaCl, atmrp5-2 seedlings accumulated less K+ and more Na+ than those of the wild type. These observations suggest that AtMRP5 is a putative sulfonylurea receptor that is involved in K+ homeostasis and, thus, also participates in the NaCl stress response.
Localization in urban environments by matching ground level video images with an aerial image (2008)

This paper presents the design of a monocular vision based particle filter localization system for urban settings that uses aerial orthoimagery as the reference map. One of the design objectives is to provide a low cost method for outdoor localization using a single camera. This relaxes the need for global positioning system (GPS) which may experience degraded reliability in urban settings. The second objective is to study the achievable localization performance with the aforementioned resources. Image processing techniques are employed to create a feature map from an aerial image, and also to extract features from camera images to provide observations that are used by a particle filter for localization.
Shear-Induced Degradation of Linear Polyacrylamide Solutions during Pre-Electrophoretic Loading (2001)

Electrophoretic channels are filled with a polymer matrix prior to their use in DNA separations. This process, called gel-loading, can be accomplished manually, using syringes, or can be automated through the use of small pumps or vacuum. The injection rate is constrained by the desire to minimize shear-induced degradation of the polymer molecules. Currently, the community lacks quantitative data with which to gauge the range of flow rates that prevent polymer degradation. In this study, measurements of the zero shear rate viscosity of linear polyacrylamide (LPA) solutions are used to determine the LPA molecular weight before and after gel-loading. The results indicate molecular degradation in polymer solutions even when injected at minimal flow rates of 1 microL/min. To correlate these rheological observations of shear-induced degradation with subsequent electrophoretic performance, the degraded solutions were used as sieving matrixes for DNA sequencing analysis. The decreases in electrophoretic resolution and increases in peak widths between sheared and nonsheared LPA solutions are related to the degradation in molecular weight experienced by the polymer solutions.
Preparation and properties of polysilsesquioxanes: Polysilsesquioxanes and flexible thin films by acid-catalyzed controlled hydrolytic polycondensation of methyl- and vinyltrimethoxysilane (1999)

Polymethylsilsesquioxane (PMS) and polyvinylsilsesquioxane (PVS) were prepared by acid-catalyzed controlled hydrolytic polycondensation of methyl- and vinyltrimethoxysilane (MTS and VTS), respectively. The spinnabilities and molecular weights of polysilsesquioxanes were easily controlled by the reaction conditions, such as the molar ratios of water, hydrochloric acid, and methanol to MTS or VTS; nitrogen flow rate; temperature; and stirring rate. PMS and PVS showed spinnability of more than 200 cm when their molecular weights were up to 42,000 (PMS) and 19,000 (PVS) Mw. Transparent, colorless, and flexible films of 0.02–0.10 mm thick were prepared by casting a 20 wt % acetone–methanol (V/V = 1) solution of PMS and PVS on a polymethylpentene shale, followed by heating at 80°C for 3 weeks. The tensile strength of the films, approximately 26 (PMS) and 17 (PVS) MPa, was found to be correlated with the structure of the polysilsesquioxanes. The surface contact angle and electroconductivity of films were also measured. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1017–1026, 1999
New Application of Bromotrimethylsilane: Elaboration of Aldehydes/Ketones into Homologous <i>α</i>,<i>β</i>‐Unsaturated Esters via <i>β</i>‐Hydroxy Esters (2005)

Abstract α,β‐Unsaturated esters are formed when β‐hydroxy esters react with bromotrimethylsilane which is generated from chlorotrimethylsilane‐lithium bromide in acetonitrile.
Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells (2012)

The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required onlyfor the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.
Weak acids as an alternative anti-microbial therapy (2020)

Weak acids such as acetic acid and N-acetyl cysteine (NAC) at pH less than their pKa can effectively eradicate biofilms due to their ability to penetrate the biofilm matrix and the cell membrane. However, the optimum conditions for their activity against drug resistant strains, and safety, need to be understood for their application to treat infections or to inactivate biofilms on hard surfaces. Here, we investigate the efficacy and optimum conditions at which weak acids can eradicate biofilms. We compared the efficacy of various mono and triprotic weak acids such as N-acetyl cysteine (NAC), acetic acid, formic acid and citric acid, in eradicating biofilms. We found that monoprotic weak acids/acid drugs can kill mucoid <i>P. aeruginosa mucA</i> biofilm bacteria provided the pH is less than their pKa, demonstrating that the extracellular biofilm matrix does not protect the bacteria from the activity of the weak acids. Triprotic acids, such as citric acid, kill biofilm bacteria at pH ​< ​pKa1. However, at a pH between pKa1 and pKa2, citric acid is effective in killing the bacteria at the core of biofilm microcolonies but does not kill the bacteria on the periphery. The efficacy of a monoprotic weak acid (NAC) and triprotic weak acid (citric acid) were tested on biofilms formed by <i>Klebsiella pneumoniae</i> KP1<i>, Pseudomonas putida</i> OUS82, <i>Staphylococcus aureus</i> 15981, <i>P. aeruginosa</i> DK1-NH57388A, a mucoid cystic fibrosis isolate and <i>P. aeruginosa</i> PA_D25, an antibiotic resistant strain. We showed that weak acids have a broad spectrum of activity against a wide range of bacteria, including antibiotic resistant bacteria. Further, we showed that a weak acid drug, NAC, can kill bacteria without being toxic to human cells, if its pH is maintained close to its pKa. Thus weak acids/weak acid drugs target antibiotic resistant bacteria and eradicate the persister cells in biofilms which are tolerant to other conventional methods of biofilm eradication.
EXPERIENCIA DE CREACIÓN DE PORTAL TEMÁTICO SOBRE PRENSA DE LA SEGUNDA GUERRA MUNDIAL. (2013)

El Archivo Fernandez-Xesta esta compuesto por una vasta coleccion de prensa editada durante la Segunda Guerra Mundial. Mediante convenio de colaboracion con la Universidad Rey Juan Carlos, se esta realizando la digitalizacion completa del archivo y la creacion de un portal donde podra consultarse toda la informacion, que actualmente asciende a 1.100.000 paginas. Fernandez-Xesta Archive consists of a vast collection of newspapers and journals published during the Second World War. By an agreement of collaboration with the Universidad Rey Juan Carlos, is being made complete file scanning and creating a portal where all information will be available, which currently amounts to 1,100,000 pages.
The Second Domain of the CD45 Protein Tyrosine Phosphatase Is Critical for Interleukin-2 Secretion and Substrate Recruitment of TCR-ζ in Vivo (1998)

The CD45 protein tyrosine phosphatase (PTPase) has been shown to regulate the activity of Lck and Fyn protein tyrosine kinases in T cells. However, it is not clear that these constitute the only CD45 substrates. Moreover, the manner by which PTPase activity and substrate recruitment are regulated, is poorly understood. Previous in vitro studies suggest that the first cytoplasmic PTPase domain (D1) of CD45 is the active PTPase, which may be regulated by an enzymatically inactive second PTPase domain (D2). However, the function of CD45 D2 in vivo is unknown. In this study, reconstitution of CD45(-) T cells with specific CD45 PTPase mutants allowed demonstration of a critical role for D2 in TCR-mediated interleukin (IL)-2 production. Specifically, replacement of CD45 D2 with that of the LAR PTPase to form a CD45/LAR:D2 chimera, abrogates CD45-dependent IL-2 production. This effect cannot be accounted for by loss of PTPase activity per se. The expression of D1 substrate-trapping mutants reveals an in vivo interaction between CD45 and TCR-zeta that is dependent on CD45 D2. Thus, cells expressing CD45 lacking D2 exhibit abnormal TCR-mediated signaling characterized by hyperphosphorylation of zeta and deficient ZAP-70 phosphorylation. These data suggest an essential role for CD45 D2 in TCR-regulated IL-2 production through substrate recruitment of the zeta chain.
RELATIONSHIP BETWEEN LIGHT CARBON DIOXIDE FIXATION AND DARK CARBON DIOXIDE FIXATION BY MARINE ALGAE1 (1971)

The ratio of CO 2 fixation in light to that in dark increases with increasing cell concentration of phytoplankton, both in natural populations of phytoplankton in the Florida Strait and in cultures of marine algae. The relevance of this phenomenon to the standard method of determining primary production in the oceans by means of carbon‐14 is discussed.