gebhart/patrepeval huggingface dataset:
Relaxation of Contracted Rabbit Tracheal and Human Bronchial Smooth Muscle by Y-27632 through Inhibition of Ca2 + Sensitization (1999)

The mechanism of Ca2+ sensitization of contraction has not been elucidated in airway smooth muscle (SM). To determine the role of a small G protein, rhoA p21, and its target protein, rho-associated coiled coil-forming protein kinase (ROCK), in receptor-coupled Ca2+ sensitization of airway SM, we studied the effect of (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexane carboxamide dihydrochloride, monohydrate (Y-27632), a ROCK inhibitor, on isometric contractions in rabbit tracheal and human bronchial SM. Y-27632 completely reversed 1 microM carbachol (CCh)-induced contraction of intact trachea with a concentration producing half-maximum inhibition of effect (IC50) of 1.29 +/- 0.2 microM (n = 5). Although 4beta-phorbol 12,13-dibutyrate (1 microM)-induced Ca2+ sensitization was relatively resistant to Y-27632 in alpha-toxin-permeabilized trachea, CCh (100 microM) plus guanosine triphosphate (GTP) (3 microM)- and guanosine 5'-O-(3'-thiotriphosphate) (10 microM)-induced contractions were relaxed completely by Y-27632 with IC50 of 1.44 +/- 0.3 (n = 6) and 1.15 +/- 0.3 microM (n = 6). Endothelin-1 (1 microM) plus GTP (3 microM)- developed force was also reversed by Y-27632 with IC50 of 4. 10 +/- 1.1 microM (n = 6) in the alpha-toxin-permeabilized bronchus. Both the rabbit and human SM expressed rhoA p21, ROCK I, and its isoform ROCK II. Collectively, rho/ROCK-mediated Ca2+ sensitization plays a central role in the sustained phase of airway SM contraction, and selective inhibition of this pathway may become a new strategy to resolve airflow limitation in asthma.
Implementation of mixture design for formulation of albumin containing enteric-coated spray-dried microparticles (2012)

Although all three Eudragit polymers can be used for enteric coating, in the microparticulate form Eudragit S resulted in higher gastric protection. Also use of HPMC along with Eudragit S resulted in further sustained release.
Display and Analysis of Patterns of Differential Activity of Drugs Against Human Tumor Cell Lines: Development of Mean Graph and COMPARE Algorithm (1989)

The objective of this study was to develop and investigate an approach to optimally detect, rank, display, and analyze patterns of differential growth inhibition among cultured cell lines. Such patterns of cellular responsiveness are produced by substances tested in vitro against disease-oriented panels of human tumor cell lines in a new anticancer screening model under development by the National Cancer Institute. In the first phase of the study, we developed a key methodological tool, the mean graph, which allowed the transformation of the numerical cell line response data into graphic patterns. These patterns were particularly expressive of differential cell growth inhibition and were conveniently amenable to further analyses by an algorithm we devised and implemented in the COMPARE computer program.
Corotated Finite Elements Made Fast and Stable (2008)

Multigrid finite-element solvers using the corotational formulation of finite elements provide an attractive means for the simulation of deformable bodies exhibiting linear elastic response. The separation of rigid body motions from the total element motions using purely geometric methods or polar decomposition of the deformation gradient, however, can introduce instabilities for large element rotations and deformations. Furthermore, the integration of the corotational formulation into dynamic multigrid elasticity simulations requires to continually rebuild consistent system matrices at different resolution levels. The computational load imposed by these updates prohibits the use of large numbers of finite elements at rates comparable to the small-strain finite element formulation. To overcome the first problem, we present a new method to extract the rigid body motion from total finite element displacements based on energy minimization. This results in a very stable corotational formulation that only slightly increases the computational overhead. We address the second problem by introducing a novel algorithm for computing sparse products of the form RKRT, as they have to be evaluated to update the multigrid hierarchy. By reformulating the problem into the simultaneous processing of a sequential data and control stream, cache miss penalties are significantly reduced. Even though the algorithm increases memory requirements, it accelerates the multigrid FE simulation by a factor of up to 4 compared to previous multigrid approaches. Due to the proposed improvements, finite element deformable body simulations using the corotational formulation can be performed at rates of 17 tps for up to 12k elements.
Immunochemotherapy of a murine thymoma with the use of idarubicin monoclonal antibody conjugates. (1988)

Idarubicin is a derivative of daunomycin and is characterized by the absence of the methoxyl group at the C-4 position. It has been reported to have greater therapeutic effect than daunomycin. Idarubicin was chemically coupled to a monoclonal antibody to the murine Ly-2.1 alloantigen and the cytotoxicity of the drug-monoclonal antibody conjugate versus free idarubicin was tested in vitro against Ly-2+ and Ly-2- tumor cell lines. Some loss of idarubicin activity occurred upon conjugation to the monoclonal antibody; however, antibody activity was preserved and selective cytotoxicity for the Ly-2+ cell line was observed. By contrast free idarubicin was equally cytotoxic for all cell lines (Ly-2+ and Ly-2-). Idarubicin-anti-Ly-2.1 conjugates were tested for their capacity to inhibit solid tumor growth in (Ly-2.1-, Ly-2.2+) (C57BL/6 x BALB/c)F1 mice while their nonspecific effects were monitored by histological examination. The idarubicin-anti-Ly-2.1 conjugates when injected i.v. or directly into the tumor were observed to inhibit tumor growth more effectively than idarubicin or anti-Ly-2.1 alone, with smaller tumors being completely eradicated within several days of the completion of treatment.
Two-state selection of conformation-specific antibodies (2009)

We present a general strategy for identification of conformation-specific antibodies using phage display. Different covalent probes were used to trap caspase-1 into 2 alternative conformations, termed the on-form and the off-form. These conformation-trapped forms of the protease were used as antigens in alternating rounds of selection and antiselection for antibody antigen-binding fragments (Fabs) displayed on phage. After affinity maturation, 2 Fabs were isolated with K(D) values ranging from 2 to 5 nM, and each bound to their cognate conformer 20- to 500-fold more tightly than their noncognate conformer. Kinetic analysis of the Fabs indicated that binding was conformation dependent, and that the wild-type caspase-1 sits much closer to the off-form than the on-form. Bivalent IgG forms of the Fabs were used to localize the different states in cells and revealed the activated caspase-1 is concentrated in a central structure in the cytosol, similar to what has been described as the pyroptosome. These studies demonstrate a general strategy for producing conformation-selective antibodies and show their utility for probing the distribution of caspase-1 conformational states in vitro and in cells.
Microfluidic Reactor for the Electrochemical Reduction of Carbon Dioxide: The Effect of pH (2010)

This article reports the development and characterization of a microfluidic reactor for the electrochemical reduction of carbon dioxide. The use of gas diffusion electrodes enables better control of the three-phase interface where the reactions take place. Furthermore, the versatility of the microfluidic reactor enables rapid evaluation of catalysts under different operating conditions. Several catalysts as well as the effects of electrolyte pH on reactor efficiency for reduction of to formic acid were tested. Operating at acidic pH resulted in a significant increase in performance: faradaic and energetic efficiencies of 89 and 45%, respectively, and current density of .
Idiopathic CD4 lymphocytopenia: a case of missing, wandering or ineffective T cells (2012)

Idiopathic CD4 lymphocytopenia (ICL) is a presumed heterogenous syndrome with key element low CD4 T-cell counts (below 300/mm³) without evidence of HIV infection or other known immunodeficiency. The etiology, pathogenesis, and management of ICL remain poorly understood and inadequately defined. The clinical presentation can range from serious opportunistic infections to incidentally diagnosed asymptomatic individuals. Cryptococcal and non-tuberculous mycobacterial infections and progressive multifocal leukoencephalopathy are the most significant presenting infections, although the spectrum of opportunistic diseases can be similar to that in patients with lymphopenia and HIV infection. Malignancy is common and related to opportunistic pathogens with an oncogenic potential. Autoimmune diseases are also seen in ICL with an increased incidence. The etiology of ICL is unknown. Mechanisms implicated in CD4 reduction may include decreased production, increased destruction, and tissue sequestration. New distinct genetic defects have been identified in certain patients with ICL, supporting the hypothesis of the lack of a common etiology in this syndrome. The management of ICL is focused on the treatment of opportunistic infections, appropriate prophylactic antibiotics, and close monitoring. In selected patients with life-threatening infections or profound immunodeficiency, strategies to increase T-cell counts or enhance immune function could be considered and have included interleukin-2, interferon-gamma, interleukin-7, and hematopoietic stem cell transplantation. The prognosis is influenced by the accompanying opportunistic infections and may be affected by publication bias of severe cases with unfavorable outcomes. As newer laboratory investigation techniques are being developed and targeted experimental treatments become available, our comprehension and prognosis of this rare syndrome could be significantly improved.
Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease (2001)

Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease. These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity.
On the determination of deoxyribonucleic acid-protein interaction parameters using the nitrocellulose filter-binding assay (1983)

We examine the effects of filter efficiency on DNA-protein binding data obtained by the popular nitrocellulose filter-binding assay. Graphical procedures for determining the efficiency parameter epsilon (for the efficiency of retention of DNA on the filter, per bound protein molecule) are established. Filter efficiency modified formulas for determining thermodynamic binding parameters are derived for four simple prototypes of DNA-protein binding systems. The effects of experimental error on discrimination between models are considered. Finally, we discuss conceptual errors often made in calculating binding stoichiometry from filter-binding experiments and suggest a general protocol for the analysis of filter-binding data.
Process Analytical Technology (2005)

Process analytical technology , Process analytical technology , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
Magnesium‐inhibited, TRPM6/7‐like channel in cardiac myocytes: permeation of divalent cations and pH‐mediated regulation (2004)

Cardiac tissue expresses several TRP proteins as well as a Mg2+ -inhibited, non-selective cation current (IMIC) that bears many characteristics of TRP channel currents. We used the whole-cell voltage clamp technique in pig and rat ventricular myocytes to characterize the permeation, blockage properties and regulation of the cardiac IMIC channels in order to compare them with TRP channels, in particular with Mg2+ -sensitive TRPM6 and TRPM7. We show that removing extracellular divalent cations unmasks large inward and outward monovalent currents, which can be inhibited by intracellular Mg2+. Inward currents are suppressed upon replacing extracellular Na+ by NMDG+. Divalent cations block monovalent IMIC and, at 10-20 mm, carry measurable currents. Their efficacy sequence in decreasing outward IMIC (Ni2+ = Mg2+ > Ca2+ > Ba2+) and in inducing inward IMIC (Ni2+ >> Mg2+ = Ca2+ approximately Ba2+), and their permeabilities calculated from reversal potentials are similar to those of TRPM6 and TRPM7 channels. The trivalent cations Gd3+ and Dy3+ also block IMIC in a voltage-dependent manner (delta = 0.4-0.5). In addition they inhibit the inward current carried by divalent cations. IMIC is regulated by pH. Decreasing or increasing extracellular pH decreased and increased IMIC, respectively (pH0.5 = 6.9, nH = 0.98). Qualitatively similar results were obtained on IMIC in rat basophilic leukaemia cells. These effects in cardiac myocytes were absent in the presence of high intracellular buffering by 40 mm Hepes. Our results suggest that IMIC in cardiac cells is due to TRPM channels, most probably to TRPM6 or TRPM7 channels or to their heteromultimeres.
Infinite Secondary Building Units and Forbidden Catenation in Metal-Organic Frameworks (2002)

Hochporöse Strukturen durch unendliche Kopplung von Zn-O-C-Sekundärbaueinheiten (SBUs) bilden das Grundmotiv der neuartigen metallorganischen Gerüste (MOFs) der Zusammensetzung [Zn3(OH2)(X)2]⋅4 DEF⋅2 H2O (siehe Bild, MOF-69A: X=4,4′-Biphenyldicarboxylat; MOF-69B: X=2,6-Naphthalindicarboxylat; DEF=N,N′-Diethylformamid). Die Bildung von Catenanstrukturen, die häufig in niedrigen Porositäten resultiert, wird aufgrund der unendlichen Struktur der SBUs verhindert.
Noncovalent Derivatization:  Green Chemistry Applications of Crystal Engineering (2002)

The field of crystal engineering is rapidly expanding. As our understanding of the mechanism of construction and relationship between structure and function of molecular crystals increases, it is important to recognize that this field offers significant toxicological and environmental benefits. The processes of molecular recognition and self-assembly are inherently benign in terms of its impact on human health and the environment. These benefits must be articulated and exploited.
ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor (2008)

Overexpression of the prosurvival Bcl-2 family members (Bcl-2, Bcl-xL, and Mcl-1) is commonly associated with tumor maintenance, progression, and chemoresistance. We previously reported the discovery of ABT-737, a potent, small-molecule Bcl-2 family protein inhibitor. A major limitation of ABT-737 is that it is not orally bioavailable, which would limit chronic single agent therapy and flexibility to dose in combination regimens. Here we report the biological properties of ABT-263, a potent, orally bioavailable Bad-like BH3 mimetic (K(i)'s of <1 nmol/L for Bcl-2, Bcl-xL, and Bcl-w). The oral bioavailability of ABT-263 in preclinical animal models is 20% to 50%, depending on formulation. ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim), leading to the initiation of apoptosis within 2 hours posttreatment. In human tumor cells, ABT-263 induces Bax translocation, cytochrome c release, and subsequent apoptosis. Oral administration of ABT-263 alone induces complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 exhibits modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. These data provide the rationale for clinical trials evaluating ABT-263 in small-cell lung cancer and B-cell malignancies. The oral efficacy of ABT-263 should provide dosing flexibility to maximize clinical utility both as a single agent and in combination regimens.
Immune cells in pancreatic cancer (2014)

Pancreatic tumors are rich in immune cell infiltrates that include CD4<sup>+</sup> T-cell subsets encompassing both regulatory T cells and T<sub>H</sub>17 cells. Rather than protecting the organism by exerting an anticancer effect, these T-cell subsets promote tumor formation. Thus, re-activation of antitumor immunity should be investigated for use in pancreatic cancer prevention and therapy.
Functional properties of oat proteins modified by acylation, trypsin hydrolysis or linoleate treatment (1987)

Abstract Proteins extracted from defatted oats were chemically modified by acylation (succinylation and acetylation), potassium linoleate treatment or partial hydrolysis with trypsin. Total essential amino acid content was slightly lowered by acetylation, but unaffected by succinylation. Gel filtration chromatography showed some dissociation of oat polypeptides by succinylation, while trypsin hydrolysis caused considerable breakdown of the protein. Solubility and emulsifying properties were significantly improved by all the modifications. Fat binding capacity was improved by acylation and linoleate treatment, while water hydration capacity and foaming properties were improved by trypsin and linoleate modifications. The gelling property was improved by acylation. When meat protein was substituted with oat protein in model wieners, there was a decrease in cook yield, cohesiveness and firmness. However, when compared to the unmodified oat protein, succinylation led to an improvement in performance in an emulsified meat system.
Cooling of large molecules below 1 K and He clusters formation (2000)

We present here the design details of a high-pressure pulsed valve that generates intense supersonic jets. The measured rotational contours of Aniline indicate that temperatures lower than 0.5 K can be achieved before the formation of clusters with the He carrier gas. The spectral shifts and vibronic structure of Anthracene–Hen clusters (n=1–6) are showing some surprising features.
Fully Character-Level Neural Machine Translation without Explicit Segmentation (2017)

Most existing machine translation systems operate at the level of words, relying on explicit segmentation to extract tokens. We introduce a neural machine translation (NMT) model that maps a source character sequence to a target character sequence without any segmentation. We employ a character-level convolutional network with max-pooling at the encoder to reduce the length of source representation, allowing the model to be trained at a speed comparable to subword-level models while capturing local regularities. Our character-to-character model outperforms a recently proposed baseline with a subword-level encoder on WMT’15 DE-EN and CS-EN, and gives comparable performance on FI-EN and RU-EN. We then demonstrate that it is possible to share a single character-level encoder across multiple languages by training a model on a many-to-one translation task. In this multilingual setting, the character-level encoder significantly outperforms the subword-level encoder on all the language pairs. We observe that on CS-EN, FI-EN and RU-EN, the quality of the multilingual character-level translation even surpasses the models specifically trained on that language pair alone, both in terms of the BLEU score and human judgment.
Cell Death Inhibiting RNA (CDIR) Derived from a 3′-Untranslated Region Binds AUF1 and Heat Shock Protein 27 (2002)

Regulators of programmed cell death were previously identified using a technical knockout genetic screen. Among the elements that inhibited interferon-gamma-induced apoptosis of HeLa cells was a 441-nucleotide fragment derived from the 3'-untranslated region (UTR) of KIAA0425, a gene of unknown function. This fragment was termed cell death inhibiting RNA (CDIR). Deletion and mutation analyses of CDIR were employed to identify the features required for its anti-apoptotic activity. Single nucleotide alterations within either copy of the duplicated U-rich motif found in the CDIR sequence abolished the anti-apoptotic activity of CDIR and altered its in vitro association with a protein complex. Further analysis of the CDIR-binding complex indicated that it contained heat shock protein 27 (Hsp27) and the regulator of mRNA turnover AUF1 (heterogeneous nuclear ribonucleoprotein D). In addition, recombinant AUF1 bound directly to CDIR. Furthermore, expression of another AUF1-binding RNA element, derived from the 3'-UTR of c-myc, inhibited apoptosis. We also demonstrate that the level and the stability of p21(waf1/Cip1/sdi1) mRNA, a target of AUF1 with anti-apoptotic activity, were increased in CDIR-transfected cells. The level of mRNA and protein of Bcl-2, another anti-apoptotic gene, containing an AUF1 binding site in its 3'-UTR was also increased in CDIR-transfected cells. Our data suggest that AUF1 regulates apoptosis by altering mRNA turnover. We propose that CDIR inhibits apoptosis by acting as a competitive inhibitor of AUF1, preventing AUF1 from binding to its targets.
Broadband nuclear magnetic resonance pulses with two-dimensional spatial selectivity (1989)

Two-dimensional spatial localization can be achieved using a single nuclear magnetic resonance (NMR) pulse if the pulse is applied in the presence of a magnetic field gradient which is reorienting through two dimensions. The application of these pulses to whole-body NMR imaging systems is hampered, however, by amplitude and slew-rate constraints on the magnetic field gradients, resulting in longer pulses with relatively limited bandwidth. We describe here a variable rate method for shortening these pulses by as much as 36% for pulses limited by slew rate and 55% for pulses limited by gradient amplitude, without changing their spatial excitation profiles on resonance.
Peripheral Anti‐Inflammatory Actions of Corticotropin‐Releasing Factor (2007)

Swelling, oedema, and loss of fluids and protein from the vascular compartment are immediate responses seen in living tissues after severe injury. Peptides of the corticotropin-releasing factor (CRF) superfamily have the unusual property of preventing the vascular leakage that occurs in tissues after damage. For example, CRF decreased protein extravasation, oedema and swelling in the anaesthetized rat's paw after exposure to heat or to extreme cold, in tracheal mucosa after exposure to formaldehyde, in skeletal muscle after a knife cut, and in brain cortex after freezing. The anti-inflammatory actions of CRF were independent of steroid release or hypotensive effects. CRF was a functional antagonist of inflammatory mediators such as histamine and substance P. It inhibited neurogenic inflammation, but interactions with unmyelinated sensory neurons did not account for the wide range of CRF's anti-inflammatory activities. Localized application of CRF prevented histamine-induced leaks in the hamster cheek pouch, and displaceable binding sites to iodinated CRF were found on blood vessels and on epithelial cells in close proximity to sites of vascular leakage. These results indicated peripheral sites of action. CRF may be the first example of a peptide hormone demonstrated to have potent anti-inflammatory agonist actions in vivo.