gebhart/patrepeval huggingface dataset:
Alpha 2-macroglobulin and serum preferentially counteract the mitoinhibitory effect of transforming growth factor-beta 2 in rat hepatocytes. (1990)

Transforming growth factors-beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2) are potent, multifunctional modifiers of cellular proliferation and differentiation in many cell types. To evaluate factors which may alter the activity of the TGF-beta s during hepatocyte proliferation, we examined the influences of bovine serum and purified bovine or human alpha 2-macroglobulin (alpha 2M) on the mitoinhibitory effects of the TGF-beta in primary cultures of rat hepatocytes. The inhibitory activity of TGF-beta was evaluated by autoradiographic labeling index at 48 hours in hepatocyte cultures exposed to [3H]thymidine between hours 24 and 48 in culture. In the absence of serum or alpha 2M, TGF-beta 1 and TGF-beta 2 were equivalently potent in inhibiting S-phase DNA synthesis in hepatocytes cultured with or without epidermal growth factor. However, bovine serum and purified bovine or human alpha 2M consistently counteracted the mitoinhibitory effects of TGF-beta 2. S-phase DNA synthesis increased five- to six-fold when bovine serum (15%) or alpha 2M (200 micrograms/ml) were included with TGF-beta 2 (0.1 ng/ml) and epidermal growth factor (20 ng/ml). The mitoinhibitory effect of TGF-beta 1 was not influenced by the addition of purified bovine alpha 2M. Human alpha 2M or bovine serum counteracted inhibition by TGF-beta 1 to a lesser extent. [125I]TGF-beta 1 and 125I]TGF-beta 2 formed complexes with purified bovine alpha 2M and serum proteins migrating at identical positions to purified alpha 2M during nondenaturing polyacrylamide gel electrophoresis. However, [125I]TGF-beta 1 associated preferentially with the "fast" migrating form of alpha 2M, whereas [125I]TGF-beta 2 associated with both the "slow" and "fast" migrating forms. Inhibitory activity of TGF-beta 1 and TGF-beta 2 coeluted with alpha 2M in the high molecular weight fractions from a Sephacryl S-200 column. These results support the hypothesis that purified alpha 2M and alpha 2M in bovine serum binds both TGF-betas but preferentially counteracts the mitoinhibitory effect of TGF-beta 2 on rat hepatocytes.
Micro-scale fluid flows : the application of acoustic streaming to biomedical research (2013)

Shear stress generated by biological fluid flows in vivo plays an important role in the regulation of numerous cellular processes; these include apoptosis, cellular proliferation and differentiation, regulation of metabolism and of inflammatory responses. The effects of shear stress are particularly prevalent in cells of the cardiovascular and skeletal systems due to the haemodynamic and interstitial fluid flows respectively. The limited scope for controlling in vivo shear stress has required the research to be conducted in vitro. Within the thesis, stable cavitation microstreaming was harnessed as a method for mimicking in vivo shear stress with the aim of developing a generic method for stressing cells. Stable cavitation microstreaming is a steady fluid flow generated by the transfer of acoustic energy into a time averaged steady momentum flux as a result of viscous damping in the boundary layer of an oscillating gas bubble. Microstreaming was generated around Expancel encapsulated microbubbles (EMBs) in purpose built microfluidic devices. The devices provided controlled environments for the generation of microstreaming. Important features of the final device include adherence of microbubbles to an internal surface of the device, the minimisation of primary acoustic radiation forces and the ability to perform high throughput biological experiments on adhered cells in the device. The microstreaming flow was characterized by micro particle image velocimetry (?PIV), showing that flows possess good repeatability and controllability. H9c2 cardiomyocytes, adhered opposite to the microbubbles at a separation distance of approximately 150 ?m, were stressed with microstreaming and their viability was measured. This was carried out in order to assess the applicability of the device to biomedical research. This research is thought to be the first in depth analysis of the controllability and repeatability of microstreaming in the context of stressing cells. Furthermore, it is thought to be the first demonstration of inflicting controlled cell death by stable cavitation microstreaming at a distance of 150 ?m.
Synthesis of 1,2,3,4-Tetrahydroisoquinoline-1-Carboxylic Acid Derivatives Via Ugi Reactions (2007)

The three-component Ugi reactions of 3,4-dihydroisoquinolines, isocyanides and acids furnished 2- acyl-N-substituted-1,2,3,4-tetrahydroisoquinoline-1-carboxamides in moderate to good yields. Chiral, nonracemic acids induced only poor diastereoselectivities in the condensations. Hydrolysis of the Ugi carboxamides gave the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids, which due to their ready ability to undergo racemization, were obtained as racemic mixtures or with low enantiomeric excesses. Keywords: Ugi reaction, isoquinolines, α-amino acids
iScreen: A Merged Screen of Local System with Remote Applications in a Mobile Cloud Environment (2013)

With the convergence of cloud computing and mobile computing, mobile devices can access remote applications in a cloud environment. However, existing research work mostly focused on leveraging cloud capabilities to enhance mobile clients. Particularly, in order to access different cloud platforms and applications, specific version of clients such as Web portal, Remote Desktop, are generally required. The original display and interaction experience on the client local system are changed. This paper presents an approach named screen which keeps a consistent display and interaction experience between local and remote applications in a mobile cloud computing environment. screen consists of a three-factor merging framework including windows merging, meta-info merging and interaction merging for applications. We developed a prototype of screen for Windows applications to allow thin clients to seamlessly access remote cloud windows applications. Experimental studies show that screen can effectively merge local desktop with remote display, and mobile clients can achieve 20 frames per second when running a remote video playback application. The bandwidth usage of screen is reduced by about 10% compared to Ultra VNC. It performs better especially under high-motion scenarios.
Catalysts for Suzuki−Miyaura Coupling Processes:  Scope and Studies of the Effect of Ligand Structure (2005)

Suzuki-Miyaura coupling reactions of aryl and heteroaryl halides with aryl-, heteroaryl- and vinylboronic acids proceed in very good to excellent yield with the use of 2-(2',6'-dimethoxybiphenyl)dicyclohexylphosphine, SPhos (1). This ligand confers unprecedented activity for these processes, allowing reactions to be performed at low catalyst levels, to prepare extremely hindered biaryls and to be carried out, in general, for reactions of aryl chlorides at room temperature. Additionally, structural studies of various 1.Pd complexes are presented along with computational data that help elucidate the efficacy that 1 imparts on Suzuki-Miyaura coupling processes. Moreover, a comparison of the reactions with 1 and with 2-(2',4',6'-triisopropylbiphenyl)diphenylphosphine (2) is presented that is informative in determining the relative importance of ligand bulk and electron-donating ability in the high activity of catalysts derived from ligands of this type. Further, when the aryl bromide becomes too hindered, an interesting C-H bond functionalization-cross-coupling sequence intervenes to provide product in high yield.
Static and Dynamical Properties of Single Poly(Ethylene Glycol) Molecules Investigated by Force Spectroscopy (2000)

Molecular recognition force spectroscopy was employed to probe the mechanical and dynamical features poly(ethylene glycol) (PEG). His6 was covalently coupled to AFM tips via PEG for the specific recognition of NTA on the surface. Force-extension profiles of single molecules obtained in force-distance cycles were fitted with an extended Worm Like Chain (WLC) model with a quality of the fit σdata-fit/σdata of 1.3. The fit revealed a persistence length LP of 3.8 ± 0.02 Å and an enthalpic correction term K0 of 1561 ± 33 pN. Amplitude-distance cycles were recorded with dynamical force microscopy. Fitting with the damped linear oscillator model, using values for the persistence length and the nonlinear spring constant from force-distance cycles, yielded a fit quality σdata-fit/σdata of 1.5. Force-distance cycles calculated from amplitude-distance cycles by integration nicely agreed with simultaneously measured force-distance cycles, and even yielded an improved signal to noise ratio. This shows that no dissipative and irreversible processes occur and that the force extension profile of PEG is determined by purely elastic behavior.
Bile Acids Affect Liver Mitochondrial Bioenergetics: Possible Relevance for Cholestasis Therapy (2000)

It has been pointed out that intracellular accumulation of bile acids cause hepatocyte injury in cholestatic disease process. This study was aimed to test if cytotoxicity of these compounds is mediated through mitochondria dysfunction. Bile acids effects on isolated rat liver mitochondrial were analyzed by monitoring changes in membrane potential and mitochondrial respiration, as well as alterations in H(+) membrane permeability and mitochondrial permeability transition pore induction. Increasing concentrations of the bile acids litocholic (LCA), deoxycholic (DCA), ursodeoxycholic (UDCA), chenodeoxycholic (CDCA), glycochenodeoxycholic (GCDC), or taurochenodeoxycholic (TCDC) decrease transmembrane potential (delta psi) developed upon succinate energization. These compounds also decreased state 3 respiration and enhanced state 4. We have also demonstrated that the observed concentration-dependent stimulation of state 4 by LCA, DCA, CDCA, TCDC, and GCDC, is associated with an enhanced permeability of mitochondria to H(+). Addition of LCA, DCA, CDCA, TCDC, GCDC, and UDCA to mitochondria energized with succinate resulted in a dose-dependent membrane depolarization and stimulation of mitochondrial permeability transition. Tauroursodeoxycholate (TUDC) elicited no significant effect on succinate-supported mitochondrial bioenergetics. In contrast, in the presence of glycoursodeoxycholic (GUDC), delta psi increases as a function of bile salt concentration. The results of this investigation demonstrate that at toxicologically relevant concentrations, most but not all bile acids alter mitochondrial bioenergetics, so impairment of mitochondrial function can be clinically relevant for patients with cholestasis.
Altered tumor antigen peptide vaccines and their application in oncotherapy (2008)

Tumor antigenic peptide vaccines,which have been adapted with altered peptide ligand (APL) and adjuvant to improve cytotoxic T lymphocyte response,include vaccines of different originations. These vaccines are orginated from malignant melanoma differentiation, HER2, NY- ESO-1, carcinoembryonic antigen and etc. Recently,great advances have been made in the related alteration methods,peptide designing principles and cytotoxic T lymphocyte response improvement mechanisms of these peptide vaccines. Furthermore,the vac- cines are showing satisfying pedormances in clinical treatments.

Key words: 
Cancer vaccine;  Antigenic peptide;  Protein alteration
A CMOS optical/potential image sensor with 7.5&amp;#956;m pixel size for on-chip neural and DNA spot sensing (2005)

An optical/potential CMOS image sensor was designed and fabricated for bioimaging applications. The image sensor is capable to simultaneously sense an optical image and an on-chip potential image. Target applications of the sensor are on-chip (optical + potential) neural imaging and on-chip DNA microarray sensing. The sensor has a QCIF (176 &#215; 144) pixel array with alternatively aligned optical/potential sensing pixels. The pixel size is 7.5 &#956;m &#215; 7.5 &#956;m. The potential resolution is confirmed to be better than 10 mV. An on-chip fluorescence imaging of a mouse's hippocampus was performed to demonstrate that fluorescence imaging is possible with on-chip configuration.
Effects of 17 months treatment using recombinant insulin‐like growth factor‐I in two children with growth hormone insensitivity (Laron) syndrome (1993)

Treatment of two patients with growth hormone insensitivity syndrome using 40 micrograms/kg of IGF-I twice a day resulted in increased linear bone growth and bone mineralization as well as increased bone maturation without remarkable adverse events. After 1 year of therapy, growth response could no longer be observed in these two patients.
Inhibition of Interleukin-1- -Induced Nitric Oxide Synthase in Vascular Smooth Muscle and Full Reversal of Interleukin-1- -Induced Hypotension by N -Amino-L-arginine (1992)

Administration of inhibitors of nitric oxide synthase can reverse the pathological cardiovascular effects of IL-1 at concentrations that do not interfere with the potentially useful immunoproliferative or tumoricidal effects of this cytokine. In the context of the current clinical trials of IL-1, this finding would represent a very significant advantage.
The α‐to‐β Conformational Transition of Alzheimer's Aβ‐(1–42) Peptide in Aqueous Media is Reversible: A Step by Step Conformational Analysis Suggests the Location of β Conformation Seeding (2006)

Current views of the role of beta-amyloid (Abeta) peptide fibrils range from regarding them as the cause of Alzheimer's pathology to having a protective function. In the last few years, it has also been suggested that soluble oligomers might be the most important toxic species. In all cases, the study of the conformational properties of Abeta peptides in soluble form constitutes a basic approach to the design of molecules with "antiamyloid" activity. We have experimentally investigated the conformational path that can lead the Abeta-(1-42) peptide from the native state, which is represented by an alpha helix embedded in the membrane, to the final state in the amyloid fibrils, which is characterized by beta-sheet structures. The conformational steps were monitored by using CD and NMR spectroscopy in media of varying polarities. This was achieved by changing the composition of water and hexafluoroisopropanol (HFIP). In the presence of HFIP, beta conformations can be observed in solutions that have very high water content (up to 99 % water; v/v). These can be turned back to alpha helices simply by adding the appropriate amount of HFIP. The transition of Abeta-(1-42) from alpha to beta conformations occurs when the amount of water is higher than 80 % (v/v). The NMR structure solved in HFIP/H2O with high water content showed that, on going from very apolar to polar environments, the long N-terminal helix is essentially retained, whereas the shorter C-terminal helix is lost. The complete conformational path was investigated in detail with the aid of molecular-dynamics simulations in explicit solvent, which led to the localization of residues that might seed beta conformations. The structures obtained might help to find regions that are more affected by environmental conditions in vivo. This could in turn aid the design of molecules able to inhibit fibril deposition or revert oligomerization processes.
Obesity Without Sleep Apnea Is Associated With Daytime Sleepiness (1998)

Daytime sleepiness is a morbid characteristic of obese patients with a potentially significant impact on their lives and public safety. Daytime sleepiness in individuals with obesity appears to be related to a metabolic and/or circadian abnormality of the disorder.
Combined Rational Design and a High Throughput Screening Platform for Identifying Chemical Inhibitors of a Ras-activating Enzyme (2015)

The Ras family small GTPases regulate multiple cellular processes, including cell growth, survival, movement, and gene expression, and are intimately involved in cancer pathogenesis. Activation of these small GTPases is catalyzed by a special class of enzymes, termed guanine nucleotide exchange factors (GEFs). Herein, we developed a small molecule screening platform for identifying lead hits targeting a Ras GEF enzyme, SOS1. We employed an ensemble structure-based virtual screening approach in combination with a multiple tier high throughput experimental screen utilizing two complementary fluorescent guanine nucleotide exchange assays to identify small molecule inhibitors of GEF catalytic activity toward Ras. From a library of 350,000 compounds, we selected a set of 418 candidate compounds predicted to disrupt the GEF-Ras interaction, of which dual wavelength GDP dissociation and GTP-loading experimental screening identified two chemically distinct small molecule inhibitors. Subsequent biochemical validations indicate that they are capable of dose-dependently inhibiting GEF catalytic activity, binding to SOS1 with micromolar affinity, and disrupting GEF-Ras interaction. Mutagenesis studies in conjunction with structure-activity relationship studies mapped both compounds to different sites in the catalytic pocket, and both inhibited Ras signaling in cells. The unique screening platform established here for targeting Ras GEF enzymes could be broadly useful for identifying lead inhibitors for a variety of small GTPase-activating GEF reactions.
Combination chemotherapy of carboplatin and paclitaxel for advanced/metastatic salivary gland carcinoma patients: differences in responses by different pathological diagnoses (2016)

Salivary gland cancer patients showed a moderate clinical response to the combination chemotherapy of carboplatin and paclitaxel. The objective response rates differed according to the pathological diagnoses, but there were no significant differences in prognoses.
Discovery of a Potent Class I Protein Arginine Methyltransferase Fragment Inhibitor (2016)

Protein methyltransferases (PMTs) are a promising target class in oncology and other disease areas. They are composed of SET domain methyltransferases and structurally unrelated Rossman-fold enzymes that include protein arginine methyltransferases (PRMTs). In the absence of a well-defined medicinal chemistry tool-kit focused on PMTs, most current inhibitors were identified by screening large and diverse libraries of leadlike molecules. So far, no successful fragment-based approach was reported against this target class. Here, by deconstructing potent PRMT inhibitors, we find that chemical moieties occupying the substrate arginine-binding site can act as efficient fragment inhibitors. Screening a fragment library against PRMT6 produced numerous hits, including a 300 nM inhibitor (ligand efficiency of 0.56) that decreased global histone 3 arginine 2 methylation in cells, and can serve as a warhead for the development of PRMT chemical probes.
Age-Dependent Replication of Respiratory Syncytial Virus in the Cotton Rat (2002)

Despite the documented disease burden of respiratory syncytial virus (RSV) in the elderly, little is known about the underlying risk factors or pathogenesis of RSV in a geriatric population. This report describes an age-dependent change of RSV clearance in the lung and nose of the cotton rat. Six days postinfection with RSV, lung and nose viral titers were significantly higher in all older age groups as compared with 4- to 6-week old cotton rats (P < 0.05). When comparing the 4- to 6-week old animals to the 15- to 16-month old animals 6 days postinfection, there was over an 800- and 100-fold increase in lung and nose viral titers, respectively. The cotton rat may prove to be a useful model in eliciting mechanisms of severe RSV disease in the elderly.
Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations. (1983)

The arrhythmogenic role of increased dispersion of repolarization (dispersion) was studied in 23 open-chest dogs using six simultaneously recorded monophasic action potentials (MAPs) from the ventricular surface and programmed ventricular premature stimulation (VPS). Increased dispersion was induced by generalized hypothermia (29 degrees C) and regional warm blood (38-43 degrees C) perfusion through a coronary artery branch. Hypothermia and regional warm blood perfusion increased maximum dispersion from 13 +/- 10 to 111 +/- 16 msec (p less than 0.001), predominantly because of the increased MAP duration difference (10 +/- 15 vs 97 +/- 16 msec, p less than 0.001). The maximal difference between activation times was not significantly changed, but the QRS duration increased from 47 +/- 6 to 52 +/- 7 msec (p less than 0.01). Ventricular arrhythmia did not occur spontaneously but was induced by a single VPS in all 23 dogs during hypothermia and regional warm blood perfusion when dispersion reached a critical magnitude. The critical magnitude of dispersion required to induce ventricular arrhythmia was documented in 16 dogs by stepwise increments or decrements of dispersion. In four dogs, an increase in atrial pacing rate of 24 beats/min prevented induction of ventricular arrhythmia by decreasing dispersion from a critical magnitude of 103 +/- 5 msec to a nonarrhythmogenic value of 86 +/- 9 msec (p less than 0.05). In six dogs, we compared the stimulation site-dependent effects of VPS applied in the region with short and long MAPs. In all dogs, ventricular arrhythmia was inducible only by VPS from the region with a short MAP. Premature impulses from this region propagated more slowly than those from the region with a long MAP. Our results show that the large dispersion of repolarization facilitates the development of a conduction delay necessary to induce sustained arrhythmia by an early premature stimulus applied at the site with a short MAP.
Cathepsins mediate tumor metastasis (2013)

Cathepsins are highly expressed in various human cancers, associated with tumor metastasis. It is superfamily, concluding A, B, C, D, E, F, G, H, L, K, O, S, V, and W family members. As a group of lysosomal proteinases or endopeptidases, each member has a different function, playing different roles in distinct tumorigenic processes such as proliferation, angiogenesis, metastasis, and invasion. Cathepsins belong to a diverse number of enzyme subtypes, including cysteine proteases, serine proteases and aspartic proteases. The contribution of cathepsins to invasion in human cancers is well documented, although the precise mechanisms by which cathepsins exert their effects are still not clear. In the present review, the role of cathepsin family members in cancer is discussed.