gebhart/patrepeval huggingface dataset:
Long-acting three-drug combination anti-HIV nanoparticles enhance drug exposure in primate plasma and cells within lymph nodes and blood (2014)

Insufficient HIV drug levels in lymph nodes have been linked to viral persistence. To overcome lymphatic drug insufficiency, we developed and evaluated in primates a lipid-drug nanoparticle containing lopinavir, ritonavir, and tenofovir. These nanoparticles produced over 50-fold higher intracellular lopinavir, ritonavir and tenofovir concentrations in lymph nodes compared to free drug. Plasma and intracellular drug levels in blood were enhanced and sustained for 7 days after a single subcutaneous dose, exceeding that achievable with current oral therapy.
Stereoselective synthesis of exocyclic alkenes via zirconium-promoted alkyl-diene coupling (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective synthesis of exocyclic alkenes via zirconium-promoted alkyl-diene couplingEiichi Negishi and Steven R. MillerCite this: J. Org. Chem. 1989, 54, 26, 6014–6016Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://pubs.acs.org/doi/10.1021/jo00287a008https://doi.org/10.1021/jo00287a008research-articleACS PublicationsRequest reuse permissionsArticle Views355Altmetric-Citations40LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The Primary Structure of High Molecular Mass Urokinase from Human Urine. The Complete Amino Arid Sequence of the A Chain (1982)

The complete sequence of 157 amino acids of the light (A) chain of high molecular mass urokinase from human urine was determined. The fragmentation strategy included cyanogen bromide cleavage of the S-carboxymethylated A chain at the methionine and/or tryptophan residues and use of the specific endoproteinase Lys-C. For sequence determination automated solid- or liquid-phase techniques of Edman degradation were used. C-terminal amino acids of the A chain were determined by consecutive treatment with carboxypeptidase A and B. The amino acid sequence obtained revealed a significant homology to peptide chains of other serine proteinases. Accordingly, the sequence of the A chain can be divided into three domains: 1) The growth factor domain with homologies to murine epidermal growth factor and a particular sequence of bovine clotting factor X, 2) The "kringle" domain with homologies to "kringle" structures, e.g. in plasminogen, and 3) the connecting peptide domain containing the A1 chain of low molecular mass urokinase. Together with the amino acid sequence of the B chain, which was presented by us in an earlier communication, the sequence data presented complete the primary structure of high molecular mass urokinase from human urine.
Developing an Ensembled Machine Learning Prediction Model for Marine Fish and Aquaculture Production (2021)

The fishing industry is identified as a strategic sector to raise domestic protein production and supply in Malaysia. Global changes in climatic variables have impacted and continue to impact marine fish and aquaculture production, where machine learning (ML) methods are yet to be extensively used to study aquatic systems in Malaysia. ML-based algorithms could be paired with feature importance, i.e., (features that have the most predictive power) to achieve better prediction accuracy and can provide new insights on fish production. This research aims to develop an ML-based prediction of marine fish and aquaculture production. Based on the feature importance scores, we select the group of climatic variables for three different ML models: linear, gradient boosting, and random forest regression. The past 20 years (2000–2019) of climatic variables and fish production data were used to train and test the ML models. Finally, an ensemble approach named voting regression combines those three ML models. Performance matrices are generated and the results showed that the ensembled ML model obtains R2 values of 0.75, 0.81, and 0.55 for marine water, freshwater, and brackish water, respectively, which outperforms the single ML model in predicting all three types of fish production (in tons) in Malaysia.
Application of bulk deformation methods for microstructural and material property improvement and residual stress and distortion control in additively manufactured components (2016)

Many additively manufactured (AM) materials have properties that are inferior to their wrought counterparts, which impedes industrial implementation of the technology. Bulk deformation methods, such as rolling, applied in-process during AM can provide significant benefits including reducing residual stresses and distortion, and grain refinement. The latter is particularly beneficial for titanium alloys where the normally seen large prior β grains are converted to a fine equiaxed structure – giving isotropic mechanical properties that can be better than the wrought material. The technique is also beneficial for aluminium alloys where it enables a dramatic reduction in porosity and improved ductility.
Double-pass Fourier transform imaging spectroscopy (2004)

Fourier-Transform Imaging Spectroscopy (FTIS) has recently become a widely used tool for spectral imaging of biological fluorescent samples. Here we report on a novel double-pass FTIS system, that is capable of obtaining an excitation as well as an emission spectrum of the fluorescent sample with only a single sweep of the interferometer. This is achieved by modifying an existing FTIS system, placing the excitation source before the interferometer so as to spectrally modulate the excitation as well as the detection. An analysis of the acquired signal allows for the reconstruction of the excitation as well as the emission spectrum of each fluorophore assuming an independence of the two spectra for each fluorophore. Due to the patterned excitation generated by the Sagnac interferometer a substantial degree of optically sectioning is achieved at excitation wavelengths. Further analysis of the acquired data also enables the generation of optically sectioned emission images. A theoretical analysis and experimental data based on fluorescent beads are presented.
Kinetics of Hepadnavirus Loss from the Liver during Inhibition of Viral DNA Synthesis (2001)

Hepadnaviruses replicate by reverse transcription, which takes place in the cytoplasm of the infected hepatocyte. Viral RNAs, including the pregenome, are transcribed from a covalently closed circular (ccc) viral DNA that is found in the nucleus. Inhibitors of the viral reverse transcriptase can block new DNA synthesis but have no direct effect on the up to 50 or more copies of cccDNA that maintain the infected state. Thus, during antiviral therapy, the rates of loss of cccDNA, infected hepatocytes (1 or more molecules of cccDNA), and replicating DNAs may be quite different. In the present study, we asked how these losses compared when woodchucks chronically infected with woodchuck hepatitis virus were treated with L-FMAU [1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl) uracil], an inhibitor of viral DNA synthesis. Viremia was suppressed for at least 8 months, after which drug-resistant virus began replicating to high titers. In addition, replicating viral DNAs were virtually absent from the liver after 6 weeks of treatment. In contrast, cccDNA declined more slowly, consistent with a half-life of approximately 33 to 50 days. The loss of cccDNA was comparable to that expected from the estimated death rate of hepatocytes in these woodchucks, suggesting that death of infected cells was one of the major routes for elimination of cccDNA. However, the decline in the actual number of infected hepatocytes lagged behind the decline in cccDNA, so that the average cccDNA copy number in infected cells dropped during the early phase of therapy. This observation was consistent with the possibility that some fraction of cccDNA was distributed to daughter cells in those infected hepatocytes that passed through mitosis.
Inhibitors of TACE and Caspase-1 As Anti-inflammatory Drugs (2005)

TNF-alpha neutralising agents such as Infliximab (Remicade), Etanercept (Enbrel) and the IL-1 receptor antagonist Anakinra (Kineret), are currently used clinically for the treatment of many inflammatory diseases such as Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis and psoriasis. These protein preparations are expensive to manufacture and administer, need to be injected and can cause allergic reactions. An alternative approach to lowering the levels of TNF-alpha and IL-1beta in inflammatory disease, is to inhibit the enzymes that generate these cytokines using cheaper small molecules. This paper is a broad overview of the progress that has been achieved so far, with respect to small molecule inhibitor design and pharmacological studies (in animals and humans), for the metalloprotease Tumour Necrosis Factor-alpha Converting Enzyme (TACE) and the cysteine protease Caspase-1 (Interleukin-1beta Converting Enzyme, ICE). Inhibitors of these two enzymes are currently considered to be good therapeutic targets that have the potential to provide relatively inexpensive and orally bioavailable anti-inflammatory agents in the future.
Comparison of tenoxicam and bromazepan in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trial (1996)

Fibromyalgia is a painful syndrome of non-articular origin, predominantly involving muscles, and the commonest cause of chronic widespread musculoskeletal pain. The diversity of therapeutic programs for patients with fibromyalgia reflects both the lack of a known pathophysiology for this disorder and the low efficacy of the current therapies. We studied the efficacy of tenoxicam and bromazepan in the treatment of patients with fibromyalgia. One hundred and sixty-four patients from our Rheumatology Outpatient Clinic fulfilling the American College of Rheumatology criteria for the classification of fibromyalgia, with widespread pain at study entry. Each of the 164 patients was randomly assigned to 1 of 4 treatment groups: double placebo (P), tenoxicam (20 mg) + placebo (T), bromazepan (3 mg) + placebo (B)m or tenoxicam (20 mg) + bromazepan 3 mg (TB). Patient global assessment of disease, pain, sleep quality, morning stiffness, and number of tender points were evaluated at baseline and 8 weeks afterwards. At the end of the trial, 17%, 10%, 12%, and 29% of the P, T, B, and TB patients, respectively, had clinical improvement. A statistically significant difference was found only between the T and TB groups. Our data indicate that treatment with tenoxicam + bromazepan can be effective for some patients with fibromyalgia, but the differences with the placebo group were neither clinically nor statistically significant.
Compromiso vascular en la encefalitis herpética (1997)

Describimos el caso de un paciente de 30 años de edad que desarrolla una encefalitis fatal par Herpes simple, en cuyos hallazgos de necropsia se destaca un compromiso vascular cerebral secundario. Se discute In posibilidad de que en la encefalitis herpética pueden presentarse dos tipos de compromiso vascular: uno reconocido desde hace tres décadas, la vasculomielinopatía diseminada, y otro, una forma de vasculitis séptica.
A Programmable Frequency Multiplier-by-29 Architecture for Millimeter Wave Applications (2015)

This paper presents an original mmW frequency multiplier that provides the channel center frequencies of the IEEE 802.15.3c standard from a much lower and fixed frequency of 2.16 GHz. It is composed of a voltage-controlled oscillator (VCO) whose supply is periodically switched on-and-off by the input signal, providing Periodically Repeated Oscillations Train (PROT). This multi-harmonic signal is injected into an oscillator (ILO) that locks onto the harmonic of interest, providing a continuous wave sinusoidal signal in the 60 GHz band. The CMOS 40 nm circuit consumes 32 mW and occupies only 0.07 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . A theoretical approach on the synchronization of the PROT signal generator and the ILO is proposed, based on custom approximated solutions of the Van der Pol oscillator and highlighting new synchronization phenomena. Based on this theory, this novel programmable multiplication technique requires a unique fixed low frequency reference to perform multi-channel mmW LO generation. The phase noise of the output LO signal is only limited by the input low frequency reference phase noise and the frequency ratio between the output and the input signals. Thus, a 60 GHz signal has been generated with this technique with a record phase noise of -104 dBc/Hz@1 MHz offset.
Human endothelial cells inhibit BMSC differentiation into mature osteoblasts in vitro by interfering with osterix expression (2006)

It is well accepted, that there is communication between osteoblasts and endothelial cells. However, the influence of endothelial cells on the differentiation of bone precursors into mature osteoblasts is not yet well understood. We therefore studied the effect of human umbilical vein endothelial cells (HUVEC) on human bone marrow stromal cell (BMSC) differentiation towards an osteoblastic phenotype by culturing them in two different types of HUVEC-BMSC cultures (indirect contact, HUVEC-conditioned medium). Typical bone markers (45Ca incorporation, ALP activity, and gene expression of collagen 1 (COL1), osteonectin (ON), matrix metalloproteinase 13 (MMP-13), bone morphogenetic protein 2 (BMP-2)) and transcription factors (Runx2, osterix (OSX)) were evaluated at different time points. The effect of stimulating HUVEC with vascular endothelial growth factor (VEGF) before co-cultures with BMSC was also evaluated. As expected, BMSC in osteogenic medium (OM) (with dexamethasone) differentiated towards the osteoblastic phenotype, as measured by increased matrix mineralization, high ALP activity, and elevated expression of specific osteoblastic marker genes, when compared to BMSC in non-OM. HUVEC reversibly inhibited osteoblastic differentiation of BMSC in OM, independent of the co-culture type. When HUVEC were removed from the cultures, BMSC differentiated into osteoblasts, albeit at a faster rate than BMSC that were never co-cultured with HUVEC. Stimulation of HUVEC with VEGF before co-culture enhanced the inhibitory effect of HUVEC on BMSC differentiation. This inhibitory effect was connected to a reversible suppression of OSX gene expression and was specific to endothelial cells. We conclude that HUVEC can inhibit dexamethasone-induced BMSC differentiation into osteoblasts in vitro, by interfering with OSX expression, thereby arresting BMSC differentiation at a preosteoblastic stage.
Cardiac Hypertrophy in Spontaneously Hypertensive Rats (1974)

Ventricular weight in spontaneously hypertensive rats (F26 generation, Okamoto-Aoki strain) was significantly higher ( P < 0.001) than that in body weight-matched American Wistar and Kyoto-Wistar normotensive rats, not only among older groups of rats but also among younger groups that had not developed significant hypertension. Deoxyribonucleic acid (DNA) concentration in ventricular muscle was not different from normal in the youngest group ( P < 0.4) but was significantly reduced in the older spontaneously hypertensive rats ( P < 0.01). Plasma renin activity was significantly increased in younger spontaneously hypertensive rats before the development of established hypertension; moreover, ventricular weight and plasma renin activity were significantly correlated in younger rats ( r = 0.788, P < 0.005 for all rats, r = 0.644, P < 0.01 for spontaneously hypertensive rats). Antihypertensive therapy with either α-methyldopa or hydralazine reduced blood pressure, especially in hypertensive rats; however, ventricular weight was reduced by methyldopa ( P < 0.01) but not by hydralazine. Plasma renin activity was reduced by methyldopa but increased by hydralazine ( P < 0.01). DNA concentration was reversed toward normal by methyldopa but not by hydralazine. Similar results were obtained when methyldopa and hydralazine were given to younger rats to prevent hypertension. The changes in ventricular weight with the onset of hypertension and with its reversal or its prevention suggest that blood pressure might not be the sole factor contributing to cardiac hypertrophy in the spontaneously hypertensive rat and that the renin-angiotensin system might play a permissive role enhancing myocardial hypertrophy.
Inhibition of Myogenic Differentiation in Proliferating Myoblasts by Cyclin D1-Dependent Kinase (1995)

Although the myogenic regulator MyoD is expressed in proliferating myoblasts, differentiation of these cells is limited to the G0 phase of the cell cycle. Forced expression of cyclin D1, but not cyclins A, B, or E, inhibited the ability of MyoD to transactivate muscle-specific genes and correlated with phosphorylation of MyoD. Transfection of myoblasts with cyclin-dependent kinase (Cdk) inhibitors p21 and p16 augmented muscle-specific gene expression in cells maintained in high concentrations of serum, suggesting that an active cyclin-Cdk complex suppresses MyoD function in proliferating cells.
Di-<i>tert</i>-butyl<i>N,N</i>-Diethylphosphoramidite. A New Phosphitylating Agent for the Efficient Phosphorylation of Alcohols (1988)

Alkyl and aryl di-tert-butyl phosphates were prepared in high yields by the 1H-tetrazole-promoted phosphitylation of alkyl and aryl alcohols with di-tert-butyl N,N-diethylphosphoramidite, followed by oxidation of the resultant alkyl and aryl di-tert-butyl phosphite triesters with m-chloroperoxybenzoic acid.
Atypical teratoid/rhabdoid tumors of the central nervous system: management and outcomes (2005)

Atypical teratoid/rhabdoid tumors are malignant lesions with rapid progression. Further study is necessary to determine the efficacy of therapy.
A Facile Synthesis of Aryl Ethers of Ethynyl-Carbinols Using the Mitsunobu Reaction (1989)

Abstract The facile synthesis of a few aryl ethers of ethynyl carbinols using the Mitsunobu reaction is reported.
Direct‐conversion flat‐panel imager with avalanche gain: Feasibility investigation for HARP‐AMFPI (2008)

The authors are investigating the concept of a direct-conversion flat-panel imager with avalanche gain for low-dose x-ray imaging. It consists of an amorphous selenium (a-Se) photoconductor partitioned into a thick drift region for x-ray-to-charge conversion and a relatively thin region called high-gain avalanche rushing photoconductor (HARP) in which the charge undergoes avalanche multiplication. An active matrix of thin film transistors is used to read out the electronic image. The authors call the proposed imager HARP active matrix flat panel imager (HARP-AMFPI). The key advantages of HARP-AMFPI are its high spatial resolution, owing to the direct-conversion a-Se layer, and its programmable avalanche gain, which can be enabled during low dose fluoroscopy to overcome electronic noise and disabled during high dose radiography to prevent saturation of the detector elements. This article investigates key design considerations for HARP-AMFPI. The effects of electronic noise on the imaging performance of HARP-AMFPI were modeled theoretically and system parameters were optimized for radiography and fluoroscopy. The following imager properties were determined as a function of avalanche gain: (1) the spatial frequency dependent detective quantum efficiency; (2) fill factor; (3) dynamic range and linearity; and (4) gain nonuniformities resulting from electric field strength nonuniformities. The authors results showed that avalanche gains of 5 and 20 enable x-ray quantum noise limited performance throughout the entire exposure range in radiography and fluoroscopy, respectively. It was shown that HARP-AMFPI can provide the required gain while maintaining a 100% effective fill factor and a piecewise dynamic range over five orders of magnitude (10(-7)-10(-2) R/frame). The authors have also shown that imaging performance is not significantly affected by the following: electric field strength nonuniformities, avalanche noise for x-ray energies above 1 keV and direct interaction of x rays in the gain region. Thus, HARP-AMFPI is a promising flat-panel imager structure that enables high-resolution fully quantum noise limited x-ray imaging over a wide exposure range.
Adsorption of H<sub>2</sub>S and SO<sub>2</sub>on Bigadiç Clinoptilolite (1995)

Abstract H2S and SO2 adsorption isotherms of Bigadiç clinoptilolite and its Na−, K−, Ca−, and H−enriched forms were determined in the 0 to 100 kPa range at 25°C by using a constant volume adsorption system. Langmuir, Freundlich, Dubinin-Radushkevich (D-R), and Dubinin-Astakhov (D-A) models were applied to the isotherm data. Higher adsorption capacities and a larger increase in the amount adsorbed at higher pressures were observed for SO2, in agreement with its higher permanent dipole moment, resulting in stronger ion-dipole and dipole-dipole interactions for this molecule. The Ca-form exhibited a molecular sieving behavior for both gases, originating from the channel blockage caused by the cation locations in the sample. The highest capacities for both gases were obtained with the sample in its H-form, followed by the Na− and K-forms for SO2, parallel to the decrease in the electronegativity and ionic potential and the increase in the polarizability of the cation. In the case of H2S, the H-form was followed by the K-form, but the Na-form yielded very low adsorption capacities. Initial dissociative adsorption of H2S on certain Na sites to yield SH and OH species is thought to contribute to a more effective blocking of the channels, which were already partially blocked in this sample. Of the isotherm models tested, the D-A model explained the variations in the data better than either the Freundlich or D-R models. For the cation-gas combinations with a lower extent of channel blockage though, the Langmuir model was somewhat more representative. Lower E and n values were obtained from the D-A model for H2S on the Na-form, which may be related to the lower extent of micropore adsorption and to the presence of blocked, almost dead-end shorter channel segments in the sample. Pore volumes close to the theoretical value were estimated from the D-A parameters for SO2 adsorption.
The nonpharmacologic basis of therapeutics (1972)

Every physician who has contact with outpatients has on occasion had his grandest therapeutic regimen hopelessly confounded by a patient's bewilderment over which little white pill comes next. Every physician has also experienced the frustration of trying to extract from a new patient information on what pills he has been taking: "I have been taking a little white pill for nerves and pressure." (phenobarbital, hydrochlorthiazide, or reserpine?)