gebhart/patrepeval huggingface dataset:
An update on drug combinations for treatment of myeloma (2007)

Multiple myeloma is the second most common haematological malignancy. It is becoming increasingly manageable with conventional and high-dose chemotherapy but there remains a critical need to develop both new drugs and combinations to improve long-term outcomes. Novel biological therapies that specifically target myeloma cells and/or their microenvironmental interactions are being developed that are highly effective, both as single agents and as combinations. Chief among these new agents are the proteasome inhibitor, bortezomib, and the immunomodulatory agents, thalidomide and lenalidomide. These drugs show improved single agent activity that is enhanced in combination. However, many drugs that are being developed in this setting may only have limited single agent activity, but combination use with these and other agents represents a very exciting way of targeting important pathogenic pathways crucial in myeloma development. This represents a challenge for both drug development and clinical trial evaluation, which has the potential to revolutionise the clinical management of myeloma and a paradigm for drug development in other diseases.
Ekofisk automatic GPS subsidence measurements (2002)

A fully automatic procedure for the measurement of subsidence of many platforms in almost real time was developed. The procedure gives reliable subsidence and rate measurements. These are essential for confirming platform safety, planning of remedial work and verification of subsidence models. Automatic GPS satellite based subsidence measurements are made continuously on platforms in the North Sea Ekofisk Field area. A description of the system is given. The derivation of those parameters which give optimal measurement accuracy is discussed. GPS satellite based measurements are more attractive than seabed pressure gauge based platform subsidence measurements, but they are much cheaper to install and maintain. In addition, GPS based measurements are not subject to drift of any gauges. GPS measurements were coupled to oceanographic quantities such as the platform deck clearance. This leads to less complex offshore survey procedures.
Replicated architectures for shared window systems: a critique (1990)

Replicating applications in a shared window environment can significantly improve the performance of the resulting system. Compared to a completely centralized approach, a replicated architecture offers superior response time and reduces network load. To date, however, these advantages have been overshadowed by the equally significant synchronization problems associated with replication. In this paper we document these problems and show that the most frequent synchronization problems can be solved without changing existing software. We further indicate how some of the limitations of the resulting system can be removed by making applications or system servers collaboration-aware. Finally, we point out where general system support is needed to address the remaining deficiencies.
Speech Signal Analysis as an Alternative to Spirometry in AsthmaDiagnosis (2018)

Speech production involves the vibration of the vocal cords. Voice changes will however occur in asthma due to the inflamed lung airways. Spirometry is a well-known technique employed in diagnosis of asthma to give information on patient pulmonary function. The purpose of this research was to investigate the correlation between FEV1/FVC (Forced Expiratory Volume to Forced Vital Capacity) ratio obtained from spirometry and Harmonics-to-Noise Ratio (HNR) obtained from human speech, in order to determine whether speech analysis could be an alternative to spirometry in diagnosing asthma. Spirometry data was obtained from 150 subjects, who were asthmatic patients attending the Korle-Bu Teaching Hospital, Ghana. Speech data consisting of the vowel sounds /a:/, /e:/, /e:/, /i:/, /o:/, / כ:/, /u:/, consonant /s:/ and phrase “She sells”, was also recorded from the subjects. 33 samples were selected and analyzed to generate speech parameters with Praat software. Correlation was established between HNR from the speech signals and spirometry data FEV1/FVC. The highest correlation coefficient was observed between HNR and vowel sound /e:/ (42.08%). In conclusion, among the other speech vowels and phonemes, Harmonics-to-Noise ratio (HNR) of /e:/ sound showed the most promise to being a suitable alternative to spirometry in asthma diagnosis.
NTRK1 Fusion in Glioblastoma Multiforme (2014)

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, yet with no targeted therapy with substantial survival benefit. Recent studies on solid tumors showed that fusion genes often play driver roles and are promising targets for pharmaceutical intervention. To survey potential fusion genes in GBMs, we analysed RNA-Seq data from 162 GBM patients available through The Cancer Genome Atlas (TCGA), and found that 3' exons of neurotrophic tyrosine kinase receptor type 1 (NTRK1, encoding TrkA) are fused to 5' exons of the genes that are highly expressed in neuronal tissues, neurofascin (NFASC) and brevican (BCAN). The fusions preserved both the transmembrane and kinase domains of NTRK1 in frame. NTRK1 is a mediator of the pro-survival signaling of nerve growth factor (NGF) and is a known oncogene, found commonly altered in human cancer. While GBMs largely lacked NTRK1 expression, the fusion-positive GBMs expressed fusion transcripts in high abundance, and showed elevated NTRK1-pathway activity. Lentiviral transduction of the NFASC-NTRK1 fusion gene in NIH 3T3 cells increased proliferation in vitro, colony formation in soft agar, and tumor formation in mice, suggesting the possibility that the fusion contributed to the initiation or maintenance of the fusion-positive GBMs, and therefore may be a rational drug target.
Does cimetidine cause weight loss? (1993)

have such an interest before making the referral."" Does this happen in practice?
Performance characterization of an abiotic and fluorescent-based continuous glucose monitoring system in patients with type 1 diabetes (2014)

A continuous glucose monitoring (CGM) system consisting of a wireless, subcutaneously implantable glucose sensor and a body-worn transmitter is described and clinical performance over a 28 day implant period in 12 type 1 diabetic patients is reported. The implantable sensor is constructed of a fluorescent, boronic-acid based glucose indicating polymer coated onto a miniaturized, polymer-encased optical detection system. The external transmitter wirelessly communicates with and powers the sensor and contains Bluetooth capability for interfacing with a Smartphone application. The accuracy of 19 implanted sensors were evaluated over 28 days during 6 in-clinic sessions by comparing the CGM glucose values to venous blood glucose measurements taken every 15 min. Mean absolute relative difference (MARD) for all sensors was 11.6 ± 0.7%, and Clarke error grid analysis showed that 99% of paired data points were in the combined A and B zones.
Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators (2015)

Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function.
Coumarin-Caged dG for Improved Wavelength-Selective Uncaging of DNA (2011)

Herein we report on diethylaminocoumarin (DEACM) as a new photoremovable protecting group for 2'-deoxyguanosine in oligonucleotides. An oligonucleotide with O(6)-DEACM-caged dG was synthesized and photochemically analyzed. The DEACM group shows superior photochemical properties at 405 nm with an uncaging efficiency (ε·φ) for deprotection that is 17 times higher than that for 2-(o-nitrophenyl)-propyl NPP caging groups in the same position. Wavelength-selective deprotection in the presence of NPP groups proceeds up to 80 times faster.
Vitamin intake, recommended intake, and gender differences. (2001)

The role of vitamins in promoting good health and preventing disease is currently gaining recognition. Daily iron and folate intake should be higher in menstruating women than in men of similar age, while lower total intake of vitamins A, B, E, K, and zinc are based on body size, and recommendations are usually lower in women compared to men. Adequate daily intake can be achieved through a balanced diet for most nutrients and vitamins. Exceptions are the need for supplementation of most vitamins and folate in pregnant women and for vitamin D and calcium in older individuals.
Demonstration of high-repetition-rate tabletop soft-x-ray lasers with saturated output at wavelengths down to13.9nmand gain down to10.9nm (2005)

Saturated tabletop lasers operating at $5\phantom{\rule{0.3em}{0ex}}\mathrm{Hz}$ repetition rate with average powers $&gt;1\phantom{\rule{0.3em}{0ex}}\ensuremath{\mu}\mathrm{W}$ were demonstrated at wavelengths between 16.5 and $13.9\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$ in the $4d\phantom{\rule{0.2em}{0ex}}^{1}S_{0}--4p\phantom{\rule{0.2em}{0ex}}^{1}P_{1}$ transitions of Ni-like ions. The results were obtained using picosecond laser heating pulses with an energy of only $1\phantom{\rule{0.3em}{0ex}}\mathrm{J}$ by optimizing the angle of incidence for maximum energy deposition. Lasing was also observed for shorter wavelength transitions of the same isoelectronic sequence, with amplification in the $11.9\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$ line of Ni-like Sn approaching gain saturation, and progressively reduced gain for wavelengths as low as $10.9\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$ for Ni-like Te. These high repetition rate soft x-ray lasers will enable new applications in science and the development of unique metrology and processing tools for industry.
rlk/TXK Encodes Two Forms of a Novel Cysteine String Tyrosine Kinase Activated by Src Family Kinases (1999)

Rlk/Txk is a member of the BTK/Tec family of tyrosine kinases and is primarily expressed in T lymphocytes. Unlike other members of this kinase family, Rlk lacks a pleckstrin homology (PH) domain near the amino terminus and instead contains a distinctive cysteine string motif. We demonstrate here that Rlk protein consists of two isoforms that arise by alternative initiation of translation from the same cDNA. The shorter, internally initiated protein species lacks the cysteine string motif and is located in the nucleus when expressed in the absence of the larger form. In contrast, the larger form is cytoplasmic. We show that the larger form is palmitoylated and that mutation of its cysteine string motif both abolishes palmitoylation and allows the protein to migrate to the nucleus. The cysteine string, therefore, is a critical determinant of both fatty acid modification and protein localization for the larger isoform of Rlk, suggesting that Rlk regulation is distinct from the other Btk family kinases. We further show that Rlk is phosphorylated and changes localization in response to T-cell-receptor (TCR) activation and, like the other Btk family kinases, can be phosphorylated and activated by Src family kinases. However, unlike the other Btk family members, Rlk is activated independently of the activity of phosphatidylinositol 3-kinase, consistent with its lack of a PH domain. Thus, Rlk has two distinct isoforms, each of which may have unique properties in signaling downstream from the TCR.
Preparation and Evaluation of Thiol-Modified Gelatin Nanoparticles for Intracellular DNA Delivery in Response to Glutathione (2005)

To enhance the intracellular delivery potential of plasmid DNA using nonviral vectors, we have developed thiolated gelatin nanoparticles that can release the payload in the highly reducing environment, such as in response to glutathione. Thiolated gelatin was synthesized by covalent modification of the primary amino groups of Type B gelatin using 2-iminothiolane (Traut's reagent). The degree of thiolation of the polymers ranged from 0 to 43.71 mmol of reduced sulfhydryl (SH) groups when the amount of 2-iminothiolane was increased up to 100 mg per gram of the biopolymer. Cytotoxicity evaluations carried out by the formazan (MTS) assay showed that the thiolated gelatin prepared with 20 mg and 40 mg of 2-iminothiolane (SHGel-20 and SHGel-40) per gram of gelatin had comparable cell viability profile to that of the unmodified gelatin. In vitro release studies of fluorescein isothiocyanate (FITC)-labeled dextran (mol wt. 70 000 Da), when encapsulated in gelatin and thiolated gelatin nanoparticles (150-250 nm in diameter), was found to be affected by the presence of glutathione (GSH) in the medium. The presence of GSH was found to enhance the release by about 40% in case of thiolated gelatin and about 20% in gelatin nanoparticles under similar conditions of temperature and GSH concentrations. Qualitative and quantitative analysis of transfection in NIH-3T3 murine fibroblast cells by the nanoparticles carrying plasmid DNA encoding for enhanced green fluorescent protein (EGFP-N1) was done by fluorescence confocal microscopy and fluorescence-activated cell sorting (FACS). Qualitative results showed highly efficient expression of GFP that remained stable for up to 96 h. Quantitative results from FACS showed that the thiolated gelatin nanoparticles (SHGel-20) were significantly more effective in transfecting NIH-3T3 cells than other carrier systems examined. The results of this study show that thiolated gelatin nanoparticles would serve as a biocompatible intracellular delivery system that can release the payload in a highly reducing environment.
Synthesis and DNA-sequence selectivity of a series of mono- and difunctional 9-aminoacridine nitrogen mustards (1994)

The aim of this work was to identify nitrogen mustards that would react selectively with DNA, particularly in G-rich regions. A series of mono- and difunctional nitrogen mustards was synthesized in which the (2-chloroethyl)amino functions were connected to the N9 of 9-aminoacridine by way of a spacer chain consisting of two to six methylene units. The length of the spacer chain connecting the alkylating and putative DNA-intercalating groups was found to affect the preference for the alkylation of different guanine-N7 positions in a DNA sequence. All of the compounds reacted preferentially at G's that are followed by G as do most other types of nitrogen mustards, but the degree of selectivity was greater. The compounds reacted at much lower concentrations than were required for comparable reaction by mechlorethamine (HN2), consistent with initial noncovalent binding to DNA prior to guanine-N7 alkylation. The degree of DNA-sequence selectivity increased as the spacer-chain length decreased below four methylene units. Most strikingly, long spacer compounds reacted strongly at 5'-GT-3' sequences, whereas this reaction was almost completely suppressed when the spacer length was reduced to two or three methylenes. Mono- and difunctional compounds of a given spacer length showed no consistent difference in DNA-sequence preference.
Use of a Cytokine Gene Expression Signature in Lung Adenocarcinoma and the Surrounding Tissue as a Prognostic Classifier (2007)

CLASS-11, which consists of genes for pro- and anti-inflammatory cytokines, identifies stage I lung adenocarcinoma patients who have a poor prognosis.
Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion’s Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds (2015)

The culinary and medicinal mushroom Hericium erinaceus is widely consumed in Asian countries, but apparently not in the United States, for its nutritional and health benefits. To stimulate broader interest in the reported beneficial properties, this overview surveys and consolidates the widely scattered literature on the chemistry (isolation and structural characterization) of polysaccharides and secondary metabolites such as erinacines, hericerins, hericenones, resorcinols, steroids, mono- and diterpenes, and volatile aroma compounds, nutritional composition, food and industrial uses, and exceptional nutritional and health-promoting aspects of H. erinaceus. The reported health-promoting properties of the mushroom fruit bodies, mycelia, and bioactive pure compounds include antibiotic, anticarcinogenic, antidiabetic, antifatigue, antihypertensive, antihyperlipodemic, antisenescence, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties and improvement of anxiety, cognitive function, and depression. The described anti-inflammatory, antioxidative, and immunostimulating properties in cells, animals, and humans seem to be responsible for the multiple health-promoting properties. A wide range of research advances and techniques are described and evaluated. The collated information and suggestion for further research might facilitate and guide further studies to optimize the use of the whole mushrooms and about 70 characterized actual and potential bioactive secondary metabolites to help prevent or treat human chronic, cognitive, and neurological diseases.
Improving T cell therapy for cancer (2006)

Adoptive transfer of antigen-specific T cells has been most effective in treating cytomegalovirus (CMV) disease and Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD). Both of these diseases develop only during periods of acute immune suppression, and both involve highly immunogenic infected cells, and thus respond well to T cell therapies. In contrast, tumours that develop in the presence of a competent immune system evolve complex immune evasion strategies to avoid and subvert T cell-mediated killing. Therefore, even T cells that display potent cytotoxic activity against tumour cells in vitro may not be effective in vivo without altering the tumour:T cell balance in favour of the T cell. This review discusses several new areas of research aimed at improving adoptive T cell therapy for the treatment of cancer, including the genetic modification of antigen-specific T cells to allow them to perform better in vivo, and conditioning the host to improve in vivo expansion and function of transferred cells.
Evaluation of payload performance for a sounding rocket vacuum ultraviolet spatial heterodyne spectrometer to observe C IV λλ1550 emissions from the Cygnus Loop (2010)

The results of a project to develop a spatial heterodyne spectrometer (SHS) for a sounding rocket mission to study the Cygnus Loop, a prototypical middle-aged supernova remnant, are discussed. The goal was to obtain a radial velocity-resolved spectrum of the C IV lambdalambda1550 emission line from bright features of the Cygnus Loop, as a test for mapping the diffuse hot interstellar medium (ISM). A full Fourier-transform analysis of Cygnus Loop emission data is presented, showing lack of velocity-resolved C IV emission detection. Optics contamination is shown to be the most likely problem, and ways to eliminate this contamination for future SHS sounding rocket and satellite missions are discussed.
Failure of an inactivated vaccine against porcine reproductive and respiratory syndrome to protect gilts against a heterologous challenge with prrsv (2007)

This study was designed to evaluate the efficacy of an inactivated vaccine based on a European-type strain of porcine reproductive and respiratory syndrome virus (PRRSV) against the reproductive form of the syndrome in breeding gilts, and any congenital disease in their piglets. Five gilts were vaccinated twice, following the manufacturer's instructions, before they were inseminated. Nine additional gilts remained unvaccinated and served as positive (five gilts) and negative (four gilts) controls. A European wild-type strain genetically divergent from the vaccine strain was used to challenge the five vaccinated and five unvaccinated positive control gilts at 90 days' gestation. The vaccination of the five seronegative gilts did not produce any clinical signs or adverse reactions. However, the vaccine failed to prevent the clinical signs associated with PRRSV infection, viraemia after the challenge and transplacental infection of their piglets. The reproductive performance of the vaccinated gilts was similar to that of the unvaccinated positive controls, and there were no statistically significant differences in most of the parameters tested. However, the preweaning mortality of the piglets born to the vaccinated gilts was significantly lower than that of the piglets born to the positive control gilts.
Tyrosine kinases activate store-mediated Ca2+ entry in human platelets through the reorganization of the actin cytoskeleton (2000)

We have recently reported that store-mediated Ca(2+) entry in platelets is likely to be mediated by a reversible trafficking and coupling of the endoplasmic reticulum with the plasma membrane, a model termed 'secretion-like coupling'. In this model the actin cytoskeleton plays a key regulatory role. Since tyrosine kinases have been shown to be important for Ca(2+) entry in platelets and other cells, we have now investigated the possible involvement of tyrosine kinases in the secretion-like-coupling model. Treatment of platelets with thrombin or thapsigargin induced actin polymerization by a calcium-independent pathway. Methyl 2,5-dihydroxycinnamate, a tyrosine kinase inhibitor, prevented thrombin- or thapsigargin-induced actin polymerization. The effects of tyrosine kinases in store-mediated Ca(2+) entry were found to be entirely dependent on the actin cytoskeleton. PP1, an inhibitor of the Src family of proteins, partially inhibited store-mediated Ca(2+) entry. In addition, depletion of intracellular Ca(2+) stores stimulated cytoskeletal association of the cytoplasmic tyrosine kinase pp60(src), a process that was sensitive to treatment with cytochalasin D and PP1, but not to inhibition of Ras proteins using prenylcysteine analogues. Finally, combined inhibition of both Ras proteins and tyrosine kinases resulted in complete inhibition of Ca(2+) entry, suggesting that these two families of proteins have independent effects in the activation of store-mediated Ca(2+) entry in human platelets.
Sphingomyelin Liposomes Containing Porphyrin-phospholipid for Irinotecan Chemophototherapy (2016)

Porphyrin-phospholipid (PoP) liposomes can entrap anti-cancer agents and release them in response to near infrared (NIR) light. Doxorubicin, when remotely loaded via an ammonium sulfate gradient at a high drug-to-lipid ratio, formed elongated crystals that altered liposome morphology and could not be loaded into liposomes with higher PoP content. On the other hand, irinotecan could also be remotely loaded but did not form large crystals and did not induce liposome elongation. The loading, stability, and NIR light-triggered release of irinotecan in PoP liposomes was altered by the types of lipids used and the presence of PEGylation. Sphingomyelin, which has been explored previously for liposomal irinotecan, was found to produce liposomes with relatively improved serum stability and rapid NIR light-triggered drug release. PoP liposomes composed from sphingomyelin, cholesterol and 2 molar percent PoP rapidly released irinotecan in vivo in response to NIR irradiation as monitored by intravital microscopy and also induced effective tumor eradication in mice bearing MIA Paca-2 subcutaneous tumor xenografts.