gebhart/patrepeval huggingface dataset:
Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. (1998)

We have been developing a series of nonpeptidic, small molecule farnesyl protein transferase inhibitors that share a common tricyclic nucleus and compete with peptide/protein substrates for binding to farnesyl protein transferase. Here, we report on pharmacological and in vivo studies with SCH 66336, a lead compound in this structural class. SCH 66336 potently inhibits Ha-Ras processing in whole cells and blocks the transformed growth properties of fibroblasts and human tumor cell lines expressing activated Ki-Ras proteins. The anchorage-independent growth of many human tumor lines that lack an activated ras oncogene is also blocked by treatment with SCH 66336. In mouse, rat, and monkey systems, SCH 66336 has excellent oral bioavailability and pharmacokinetic properties. In the nude mouse, SCH 66336 demonstrated potent oral activity in a wide array of human tumor xenograft models including tumors of colon, lung, pancreas, prostate, and urinary bladder origin. Enhanced in vivo efficacy was observed when SCH 66336 was combined with various cytotoxic agents (cyclophosphamide, 5-fluorouracil, and vincristine). In a Ha-Ras transgenic mouse model, prophylactic treatment with SCH 66336 delayed tumor onset, reduced the average number of tumors/mouse, and reduced the average tumor weight/animal. In a therapeutic mode in which gavage treatment was initiated after the transgenic mice had developed palpable tumors, significant tumor regression was induced by SCH 66336 in a dose-dependent fashion. This was associated with increased apoptosis and decreased DNA synthesis in tumors of animals treated with SCH 66336. Enhanced efficacy was also observed in this model when SCH 66336 was combined with cyclophosphamide. SCH 66336 is presently being evaluated in Phase I clinical trials.
Synthesis of (S,R,R,R)-α,α′-Iminobis(methylene)bis(6-fluoro-3H,4H-dihydro-2H-1-benzopyran-2-methanol) (2007)

The β1-adrenergic antagonist (S,R,R,R)-α,α′-iminobis(methylene)bis(6-fluoro-3H,4H-dihydro-2H-1-benzopyran-2-methanol) was synthesized from natural chiral pool starting materials through an efficient, convergent synthetic strategy. The cyclization mechanism of the key step was investigated using computer modeling and is discussed.
Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells (2012)

The results of our study imply that an imbalanced glucose metabolism can reduce the functioning ability of stem cells in vivo both during ageing and during stem cell-based therapeutic interventions.
Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. (1994)

DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53 and in some cases can cause apoptosis. M1 cells, which do not express the endogenous tumor suppressor gene p53, undergo apoptosis following activation of a temperature sensitive p53 transgene, where it has been shown that bax, an important mediator of apoptosis, is a p53 target gene (Selvakumaran et al, Oncogene 9, 1791-8, 1994). Since p53 can function as a transcription factor after activation by IR, the genetic response to this stress was examined in a panel of human cells with defined p53 status. Like the p53-regulated gene gadd45, bax was rapidly induced, as measured by increased mRNA levels, in the p53 wt (wild type) human myeloid line ML-1, and it was not induced in cells lacking functional p53. However, unlike other p53-regulated genes, bax was only induced in p53 wt cells in which IR also triggered apoptosis. In the case of bcl2, which opposes bax function, mRNA levels were reduced in ML-1 cells after IR. Thus, bax appears to be an unique p53-regulated gene in that its induction by IR not only requires functional p53 but also requires that the cells be apoptosis "proficient."
Xylanase B and an arabinofuranosidase from Pseudomonas fluorescens subsp. cellulosa contain identical cellulose-binding domains and are encoded by adjacent genes (1990)

The complete nucleotide sequence of the Pseudomonas fluorescens subsp. cellulosa xynB gene, encoding an endo-beta-1,4-xylanase (xylanase B; XYLB) has been determined. The structural gene consists of an open reading frame (ORF) of 1775 bp coding for a protein of Mr 61,000. A second ORF (xynC) of 1712 bp, which starts 148 bp downstream of xynB, encodes a protein, designated xylanase C (XYLC), of Mr 59,000. XYLB hydrolyses oat spelt xylan to xylobiose and xylose, whereas XYLC releases only arabinose from the same substrate. Thus XYLB is a typical xylanase and XYLC is an arabinofuranosidase. Both enzymes bind to crystalline cellulose (Avicel), but not to xylan. The nucleotide sequences between residues 114 and 931 of xynB and xynC were identical, as were amino acid residues 39-311 of XYLB and XYLC. This conserved sequence is reiterated elsewhere in the P. fluorescens subsp. cellulosa genome. Truncated derivatives of XYLB and XYLC, in which the conserved sequence had been deleted, retained catalytic activity, but did not exhibit cellulose binding. A hybrid gene in which the 5' end of xynC, encoding residues 1-110 of XYLC, was fused to the Escherichia coli pho A' gene (encodes mature alkaline phosphatase) directed the synthesis of a fusion protein which exhibited alkaline phosphatase activity and bound to cellulose.
Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. (2002)

A correlative study was performed to address the impact of epidermal growth factor receptor (EGFR) overexpression on survival and pattern of failure in patients with advanced head and neck squamous cell carcinomas (HNSCCs) enrolled in a Phase III trial and randomized to receive conventional radiotherapy. The study population comprised 155 of 268 (58%) randomized patients with sufficient pretreatment biopsy specimens for immunohistochemical assay. The specimens were dewaxed and incubated after standard preparation with mouse monoclonal antibodies recognizing the extracellular domain of the EGFR molecule. The catalyzed product was visualized with 3,3'-diaminobenzidine Chromogen Kit and lightly counterstained with Mayer's hematoxylin. Quantitative EGFR immunohistochemistry (IHC) was done with SAMBA 4000 Cell Image Analysis System, without knowledge of the clinical outcome, to yield mean absorbance (MOD), staining index (SI), and quick score (QS). These EGFR IHC parameters were correlated with the T stage, N stage, combined stage grouping, and recursive partitioning analysis classes. Subsequently, the EGFR parameters were correlated with the outcome end points, i.e., overall survival (OS), disease-free survival (DFS), local-regional (LR) relapse, and distant metastasis rates. We found that HNSCCs exhibited a wide variation in EGFR expression (MOD, 0.2-66.0; SI, 0.3-97.0; QS, 0.01-69.9) with a relatively strong but nonlinear correlation between MOD and SI (r = 0.79). There was no correlation between EGFR expression and T stage, N stage, stage grouping, and recursive partitioning analysis classes (r = -0.07 to 0.17). The OS and DFS rates of patients with high EGFR-expressing HNSCCs (>median MOD) were highly significantly lower (P = 0.0006 and P = 0.0016, respectively) and the LR relapse rate was highly significantly higher (P = 0.0031) compared with those of patients with low EGFR-expressing HNSCCs. However, there was no difference in the distant metastasis rate between the two groups (P = 0.96). Significant correlations, although somewhat less robust than MOD, were also observed between SI and QS and the OS, DFS, and LR relapse rates. Multivariate analysis showed that EGFR expression was an independent determinant of survival and a robust independent predictor of LR relapse. In summary, this correlative study in a large series of patients revealed that EGFR expression, which varied considerably among HNSCCs, was a strong independent prognostic indicator for OS and DFS and a robust predictor for LR relapse but not for distant metastasis. The data suggest that EGFR IHC should be considered for selecting patients for more aggressive combined therapies or enrollment into trials targeting EGFR signaling pathways.
Patterned Protein Layers on Solid Substrates by Thin Stamp Microcontact Printing (1998)

Microcontact printing (μCP) is a new method of molecularly patterning surfaces on a micrometer scale. In this paper, we present the extension of microcontact printing to producing patterned layers of proteins on solid substrates. μCP avoids the use of strong acids and bases necessary in photolithographic patterning, allowing its use for patterning of proteins and other biological layers. We also describe the methods of thin stamp microcontact printing that allow printing of isolated features previously unattainable by microcontact printing. A solution of polylysine in borate-buffered saline was printed onto a glass coverslip, yielding micrometer scale features over an area of 4 cm2.
Involvement of hepatocyte growth factor/scatter factor and Met receptor signaling in hair follicle morphogenesis and cycling (2000)

HGF/SF and its receptor (Met) are principal mediators of mesenchymal-epithelial interactions in several different systems and have recently been implicated in the control of hair follicle (HF) growth. We have studied their expression patterns during HF morphogenesis and cycling in C57BL/6 mice, whereas functional hair growth effects of HGF/SF were assessed in vivo by analysis of transgenic mice and in skin organ culture. In normal mouse skin, follicular expression of HGF/SF and Met was strikingly localized: HGF/SF was found only in the HF mesenchyme (dermal papilla fibroblasts) and Met in the neighboring hair bulb keratinocytes. Both HGF/SF and Met expression peaked during the initial phases of HF morphogenesis, the stage of active hair growth (early and mid anagen), and during the apoptosis-driven HF regression (catagen). Met+ cells in the regressing epithelial strand appeared to be protected from undergoing apoptosis. Compared to wild-type controls, transgenic mice overexpressing HGF/SF under the control of the MT-1 promoter had twice as many developing HF and displayed accelerated HF development on postnatal day 3. They also showed significant catagen retardation on P17. In organ culture and in vivo, HGF/SF i.c. resulted in a significant catagen retardation. These results demonstrate an important role of HGF/SF and Met in murine hair growth control and suggest that Met-mediated signaling might be exploited for therapeutic manipulation of human hair growth disorders.-Lindner, G., Menrad, A., Gherardi, E., Merlino, G., Welker, P., Handjiski, B., Roloff, B., Paus, R. Involvement of hepatocyte growth factor/scatter factor and Met receptor signaling in hair follicle morphogenesis and cycling.
The Rat Homologue of Wiskott-Aldrich Syndrome Protein (WASP)-interacting Protein (WIP) Associates with Actin Filaments, Recruits N-WASP from the Nucleus, and Mediates Mobilization of Actin from Stress Fibers in Favor of Filopodia Formation (2002)

We cloned and characterized the rat homologue of the Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP). Rat WIP shows 86% amino acid sequence identity to human WIP. Northern analyses revealed two major mRNA species of 5.0 and 3.8 kb, which were ubiquitously expressed, though predominantly in spleen and lung. Minor species of 2.4, 1.8, 1.4, and 1.1 kb were also detected in some tissues and cell lines. Thus, WIP is subject to tissue-specific alternative splicing. WIP bound to N-WASP in vivo, as revealed by co-immunoprecipitation. Expression of WIP in rat fibroblasts revealed a clear co-localization with actin stress fibers. However, expression in tumor cells lacking actin cables did not restore these structures. Interestingly, co-expression of WIP and N-WASP resulted in redistribution of N-WASP, abrogating its dominant nuclear expression and leading to co-localization with WIP in the perinuclear area and with actin in membrane protrusions. Moreover, stress fibers and, concomitantly, the associated WIP were largely dissolved. Very similar effects were seen upon epidermal growth factor stimulation of serum-starved cells. Our results suggest that WIP might be involved in transmitting mitogenic signals to cytoskeletal functions, perhaps by modulating the subcellular localization of N-WASP. Interaction of N-WASP with WIP may in turn lead to mobilization of actin from stress fibers and nucleation of new actin filaments in filopodia.
Harmonic power mode Doppler using microbubble contrast agents: an improved method for small vessel flow imaging (1994)

By virtue of their ability to enhance the weak echoes received from flow in small blood vessels, ultrasound contrast agents render flow in a lower level of the circulation detectable to colour Doppler imaging. We combine contrast imaging with power Doppler, which is a more appropriate colour mode for contrast enhanced Doppler imaging. We demonstrate that the combination of harmonic Doppler and the enhancement of the Doppler signal by the contrast agent produces an in vivo gain of more than 30 dB in the signal-to-clutter ratio. Harmonic power Doppler imaging demonstrates flow in the cortex of the kidney to within 2 mm of the capsule, even in the presence of respiratory motion. Histological correlation of the Doppler images with sections of the cortical vasculature suggest that flow is detected in interlobular arterioles of mean diameter 44 μm. We conclude that the new method holds promise for the clinical detection of small vessel flow in moving solid tissue
Dynamical theory of migration of an adsorbed atom on solid surfaces (1976)

A dynamical theory of an adsorbed atom on solid surfaces is developed starting from a Hamiltonian which includes: (1) motion of the adsorbed atom parallel to the surface; (2) the vibration of the adsorbed atom perpendicular to the surface; (3) the lattice vibrations (phonons) of the solid; (4) the coupling between the vibration of the adsorbed atom and its parallel motion; (5) the coupling between the lattice vibrations and the parallel motion of the adsorbed atom; (6) the concerted interaction among the phonons, the vibration, and the parallel motion. Using a canonical transformation, we describe the motion of the adsorbed atom as one of a pseudomolecule formed from the adsorbed atom and the distorted lattice. An equation for the probability of finding the adsorbed atom at a lattice site is derived and the mean square displacement of the motion of the adsorbed atom is calculated. At low temperature, the migration of the adsorbed atom is coherent and the mean square displacement is proportional to the square of time. The adsorbed atom behaves like a free particle with a certain velocity. At high temperature, the migration has diffusional character and the mean square displacement is proportional to time. This is due to the interaction between the parallel motion of the adsorbed atom and phonons as well as to the one between the vibration of the adsorbed atom and phonons. At intermediate temperature, after a certain time, which becomes shorter as the temperature increases, the migration becomes diffusional. The resulting diffusion coefficient consists of two parts: one represents the diffusional character of the migration, and the other its coherent nature. The temperature dependence of the diffusional part is of the Arrhenius type, while that of the coherent part increases as temperature decreases. The coherent part is small when the interaction between the adsorbed atom and the lattice atoms is very strong. Thus the theory gives reasonable trends with respect to the variation of parameters taken into account. Comparison with existing experiments on tungsten and rhodium is briefly made to estimate the order of magnitude of the lattice distortion due to the strong interaction between the adsorbed atom and the lattice atoms.
The significance of the complement system for the pathogenesis of age-related macular degeneration — current evidence and translation into clinical application (2010)

Such data suggest that the complement system may have a significant role for developing new prophylactic and therapeutic interventions in AMD. In fact, several compounds acting on the complement pathway are currently in clinical trials. Therapeutics that modulate the complement system need to balance inhibition with preservation of sufficient functional activity in order to maintain adequate immune responses and tissue homeostasis. Specifically, targeting the dysfunction appears more adequate than a global suppression of complement activation in chronic diseases such as AMD.
Dietary moderately oxidized oil induces expression of fibroblast growth factor 21 in the liver of pigs (2012)

The present study shows for the first time that administration of an oxidized fat induces the expression of FGF21 in the liver, probably mediated by activation of PPARα. Induction of FGF21 could be involved in several effects observed in animals administered an oxidized fat.
N-(tert-Butoxycarbonyl)-N-[4- (dimethylazaniumylidene)-1,4- dihydropyridin-1-ylsulfonyl]azanide: A New Sulfamoylating Agent. Structure and Reactivity toward Amines (2001)

[structure: see text] Synthesis, structure, and reactivity toward amines of the new sulfamoylating reagent 2 are described. Compound 2 allowed sulfamoylation of amines under very mild conditions to give sulfamide derivatives in good yields.
Transparency and Bypass in Electronic Financial Markets (1993)

Electronic markets use information technology to disseminate information on prices, quantities, and buyer and supplier identities. In spite of the recognized benefits of electronic markets, increased visibility and transparency may introduce imperfections, and create profitable opportunities to bypass markets that generates the information. In the U.S. securities markets, dissemination of market data has equipped several firms to develop competing, off-exchange trading mechanisms that rely on market price data, but whose transactions bypass the established market. Concern is rising that the growing volume of trading occurring away from the main market may reduce liquidity, and increase transactions costs. A simulation model of securities trading in a continuous auction market (similar to the market structure of the New York Stock Exchange) is used to examine the market quality effects of increasing levels of trading activity through an off-exchange dealer. Market characteristics, such as transactions costs, are measured as off-exchange trading increases from zero percent to 20 percent of the total trading volume. The results indicate that competition from an alternative trading venue reduces some trading costs borne by investors. Contrary to regulatory goals, however, off-market trading expands the role of profit-seeking dealers, and lowers the probability that some investors' orders will execute.
New Multi-Channel Transcutaneous Electrical Stimulation Technology for Rehabilitation (2006)

Transcutaneous (surface) electrical stimulation (TES) is a widely applied technique for muscle atrophy treatment, muscle force training, endurance training, pain treatment, functional movement therapy, and the restoration of motor functions. We present a new TES technology based on a multi-channel stimulation approach, which allows us to perform real-time spatial and temporal variations of the electrical current density on the skin surface and in deeper tissue layers. This new approach can generate a better muscle selectivity and improved muscle activation patterns compared to state of art TES systems, which operate with predetermined electrode positions. In simulations using a finite element model (FEM) of the distal arm we could show that the nerve activation in the muscle layer is not significantly influenced by the structure of the multi-channel electrode, if the gap between elements is less than 2 mm. Experiments in healthy volunteers allowed us to measure the selectivity of single finger activations. We could also show in stroke subjects that this novel multi-channel approach was able to generate selective finger and wrist extension movements that were strong enough to overcome flexion hyperactivity. For future applications in rehabilitation a full integration of the stimulation hardware into a garment sleeve would be helpful. Once fully integrated, this new technology has a high potential to increase the ease of use, stimulation and wear comfort. It is able to improve muscle selectivity compared to state of the art TES systems, and allows the implementation of a variety of new applications for the medical and consumer market.
Rabies virus binding to an acetylcholine receptor α‐subunit peptide (1990)

The binding of 125I-labeled rabies virus to a synthetic peptide comprising residues 173-204 of the alpha 1-subunit of the nicotinic acetylcholine receptor was investigated. Binding of rabies virus to the receptor peptide was dependent on pH, could be competed with by unlabeled homologous virus particles, and was saturable. Synthetic peptides of snake venom, curaremimetic neurotoxins and of the structurally similar segment of the rabies virus glycoprotein, were effective in competing with labeled virus binding to the receptor peptide at micromolar concentrations. Similarly, synthetic peptides of the binding domain on the acetylcholine receptor competed for binding. These findings suggest that both rabies virus and neurotoxins bind to residues 173-204 of the alpha 1-subunit of the acetylcholine receptor. Competition studies with shorter alpha-subunit peptides within this region indicate that the highest affinity virus binding determinants are located within residues 179-192. A rat nerve alpha 3-subunit peptide, that does not bind alpha-bungarotoxin, inhibited binding of virus to the alpha 1 peptide, suggesting that rabies binds to neuronal nicotinic acetylcholine receptors. These studies indicate that synthetic peptides of the glycoprotein binding domain and of the receptor binding domain may represent useful antiviral agents by targeting the recognition event between the viral attachment protein and the host cell receptor, and inhibiting attachment of virus to the receptor.
A Nonpeptide Mimic of Bradykinin Blunts the Development of Hypertension in Young Spontaneously Hypertensive Rats (2000)

We tested whether FR190997, a nonpeptide B(2) agonist, prevented the development of hypertension in young spontaneously hypertensive rats (SHR), which secrete less kallikrein into the urine than do Wistar-Kyoto rats. An intra-arterial (IA) injection of FR190997 (0.3 to 30 nmol/kg) caused dose-dependent hypotension in conscious Sprague-Dawley rats. Although the maximum hypotensive potency of FR190997 equaled that of bradykinin, its action lasted approximately 10 times as long. Hoe140 (100 nmol/kg IA) significantly blocked the hypotensive response induced by FR190997 (10 nmol/kg). Atropine (100 nmol/kg IA) did not affect this response. A selective infusion of FR190997 into the renal artery induced natriuresis and diuresis in anesthetized rabbits. A continuous infusion (2 nmol. 10 mL(-1). h(-1) per rat) of FR190997 into the abdominal aorta of young SHR (6 weeks old, n=6) for 6 days significantly (P<0.05) reduced mean blood pressure to 114+/-6 (day 2) and 110+/-6 (day 5) mm Hg, from 149+/-7 and 162+/-6 mm Hg, respectively, in vehicle-infused rats (n=6). At 8 days after continuous infusion (day 14), mean blood pressure (148+/-5 mm Hg) in FR190997-infused rats remained significantly (P<0. 05) lower than that in vehicle-infused rats (190+/-6 mm Hg), almost the peak value. The mesenteric artery isolated from FR190997-treated rats (day 14) had lower contractile sensitivity to norepinephrine than that from vehicle-treated rats. These results suggested that the continuous infusion of a nonpeptide B(2) agonist may prevent hypertension if performed in the critical phase.