gebhart/patrepeval huggingface dataset:
The G226A mutant of Gs alpha highlights the requirement for dissociation of G protein subunits. (1992)

Adenylylcyclase cannot be activated by hormones or guanine nucleotide analogs in membranes from cells that express the G226A mutant form Gs alpha instead of the wild-type protein. The mutant Gs alpha protein appears incapable of undergoing the conformational change necessary for guanine nucleotide-induced dissociation of the G protein alpha subunit from the beta gamma subunit complex (Miller, R.T., Masters, S.B., Sullivan, K.A., Beiderman, B., and Bourne, H.R. (1988) Nature 334, 712-715). G226A Gs alpha was synthesized in Escherichia coli, purified, and characterized. Examination of the kinetics of dissociation of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) suggests that G226A Gs alpha is incapable of assuming the conformation necessary for high affinity binding of Mg2+ to the alpha subunit-GTP gamma S complex. Associated changes include the failure of Mg2+ and GTP gamma S to confer resistance to tryptic proteolysis upon the protein, to enhance intrinsic tryptophan fluorescence, or to cause dissociation of alpha from beta gamma. However, the GTPase activity of the mutant protein is near normal (at high Mg2+ concentrations), and the protein is capable of activating adenylylcyclase. A similar defect is present in G49V Gs alpha. Failure of G protein subunit dissociation appears to be the explanation for the phenotypic properties of cells that express G226A Gs alpha, and this mutation thus highlights the crucial nature of this reaction as a component of G protein action.
Pilot Study of Albendazole in Patients with Advanced Malignancy (2001)

Our preclinical studies have shown that the widely used antiparasitic drug albendazole has potent antiproliferative activity against colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This trial was designed to evaluate albendazole in a small number of patients (n = 7) with either HCC or CRC and hepatic metastases refractory to other forms of therapy. Albendazole was given at 10 mg/kg/day orally in two divided doses for a period of 28 days. To follow the effect of treatment, tumor markers, carcinoembryonic antigen (CEA) or alpha-feto protein (AFP), were measured routinely in these patients. A range of hematological and biochemical indices were also serially measured to monitor bone marrow, kidney or liver toxicity. Albendazole therapy resulted in a decrease in CEA in 2 patients. In the remaining 5 with measurable tumor markers, serum CEA or AFP was stabilized in 3 patients, while in the other 2, after an initial stabilization (5-10 days), the markers began to increase. In the 7 patients completing the trial, albendazole was well tolerated and there were no significant changes in any hematological, kidney or liver function tests, but 3 patients were withdrawn for severe neutropenia which was probably contributory to the death of 1 patient. These data support our previous experimental results demonstrating that albendazole has antitumor effects.
Focused Microwave‐Assisted Synthesis of 2,5‐Dihydrofuran Derivatives as Electron Acceptors for Highly Efficient Nonlinear Optical Chromophores (2003)

Highly efficient and tunable electron acceptors composed of a diverse family of 2,5‐dihydrofuran derivatives have been synthesized using single‐mode focused microwave irradiation. A very large electro‐optic coefficient and long‐term temporal stability (see Figure) have been demonstrated in a host/guest system composed of polyquinoline and the nonlinear optical chromophore shown in the Figure.
Polarization control of vertical-cavity surface-emitting lasers by electro-optic birefringence (2000)

Polarization of vertical-cavity surface-emitting lasers (VCSELs) grown on (001) GaAs substrate has been controlled by electro-optic birefringence. Birefringence was induced at the top distributed Bragg reflector by applying an electric field along the [001] direction. The cavity resonance of the polarized light along the [110] or [11̄0] direction shifted to shorter and longer wavelength, depending on the direction of the applied electric field. By varying the direction and strength of the electric field, we actively controlled the polarization of VCSELs. The dominant polarization mode occurred along the [110] direction for the negative electric field, and along the [11̄0] direction for the positive electric field.
The prognosis of non-critical limb ischaemia: a systematic review of population-based evidence. (1999)

Given the current knowledge on the prognosis of PAOD in the general population, an important task for (secondary) prevention is reserved for the general practitioner. Further research is required to document the course and prognosis of asymptomatic PAOD patients.
Risk assessment of the mycotoxin ochratoxin A. (1989)

Ochratoxin A (OA) is a mycotoxin which has been found to occur in foods of plant origin, in edible animal tissues, as well as in human blood sera and tissues. The ability of OA to move up the food chain is aided by its long half-life in certain edible animal species. In this report, an evaluation of the health risks to Canadians due to the presence of OA in food products is presented. The first part of the report deals with the physicochemical aspects, mycology, laboratory production, analytical methods, and natural occurrence in plant products, animal products, and human tissues. The stability of OA in foods and feeds, the effects of food processing, and the removal from foods and feeds by physiochemical means are also discussed. From these data, the worst case estimate for the daily exposure of Canadians to OA, from the consumption of pork-based food products and cereal foods, is approximately 5 ng OA/kg body wt (mean of eaters) for young children, the highest consumption group on a body weight basis. The second part of the report deals with the metabolic disposition as well as the available toxicity database for OA in laboratory animals, farm animals, and humans. The major target for OA toxicity in all mammalian species tested is the kidney, and endemic nephropathies affecting livestock as well as humans have been attributed to OA. OA is also teratogenic, and in the fetus the major target is the developing central nervous system. Recent studies have provided "clear evidence" of the carcinogenicity of OA in two rodent species. OA was found to be nonmutagenic in various microbial and mammalian gene mutation assays, but weak genotoxic activity to mammalian cells was noted. In addition, OA was found to suppress immune function. Based on the NTP carcinogenicity study with OA in rats, the estimated tolerable daily intake in humans ranges from 0.2 to 4.2 ng OA/kg body wt, depending on the method of extrapolation used. In view of the toxic properties of OA, it is recommended that exposure to OA be kept to a minimum. In Canada, further monitoring programs are required to better define the overall residue profile of OA in cereal grains, animal feeds, animal food products, and human blood. Such data are required to better assess dietary exposure and to ascertain the need for regulatory controls or other control mechanisms.
Rapidly Self-Expandable Polymeric Stents with a Shape-Memory Property (2007)

A novel biodegradable stent, made of chitosan films cross-linked with an epoxy compound, with a shape-memory property was developed. To reduce their crystallinity, glycerol and poly(ethylene oxide) were blended in the chitosan films. The mechanical properties of the prepared stent were studied using a commercially available metallic stent as a control. After blending, the ductility of the chitosan films was improved, and the compressive strength of the stent was significantly enhanced. The metallic stent could tolerate elastic deformations of 10% before becoming irreversibly deformed, while the polymeric stent was able to withstand deformations up to 30% and still regain its original configuration. The developed stent could rapidly expand ( approximately 150 s) from its crimped (temporary) to fully expanded (permanent) states stimulated by hydration, which is advantageous considering avoiding its migration during in vivo deployment. In the preliminary animal study, the implanted stent was found to be intact, and no thrombus formation was seen in the stent-implanted vessel. This degradable stent can be an attractive alternative to metallic stents and may serve as a useful vehicle for local drug delivery.
Organically Doped Metals—A New Approach to Metal Catalysis: Enhanced Ag‐Catalyzed Oxidation of Methanol (2007)

Abstract We report here a new approach for the modification of the performance of metal catalysts: organic doping of the metal. Specifically, we report that the doping of Ag with Congo Red (CR@Ag) significantly improves the performance of Ag as a catalyst for methanol oxidation to formaldehyde, outperforming both pure Ag and CR‐coated Ag (CR/Ag) in terms of lowering the temperature needed for maximal conversion by 100 °C, lowering the temperature by 200 °C to reach the maximal selectivity (aldehyde formation), and increasing the maximal space velocity by a factor of two. We were led to this discovery by a detailed investigation of the thermal behavior (thermogravimetric and differential thermal analysis and mass spectroscopy) of CR@Ag under an oxidative atmosphere, which has indicated that the metal is strongly catalyzing the CR oxidation, and which pointed to the relevant temperature for activation of the catalyst.
Large ray packets for real-time Whitted ray tracing (2008)

In this paper, we explore large ray packet algorithms for acceleration structure traversal and frustum culling in the context of Whitted ray tracing, and examine how these methods respond to varying ray packet size, scene complexity, and ray recursion complexity. We offer a new algorithm for acceleration structure traversal which is robust to degrading coherence and a new method for generating frustum bounds around reflection and refraction ray packets. We compare, adjust, and finally compose the most effective algorithms into a real-time Whitted ray tracer. With the aid of multi-core CPU technology, our system renders complex scenes with reflections, refractions, and/or point-light shadows anywhere from 4–20 FPS.
Selective Targeting of Melanoma and APCs Using a Recombinant Antibody with TCR-Like Specificity Directed Toward a Melanoma Differentiation Antigen (2003)

Tumor-associated, MHC-restricted peptides, recognized by tumor-specific CD8(+) lymphocytes, are desirable targets for novel approaches in immunotherapy because of their highly restricted fine specificity. Abs that recognize these tumor-associated MHC-peptide complexes, with the same specificity as TCR, would therefore be valuable reagents for studying Ag presentation by tumor cells, for visualizing MHC-peptide complexes on cells, and eventually for developing new targeting agents for cancer immunotherapy. To generate molecules with such a unique, fine specificity, we immunized HLA-A2 transgenic mice with a single-chain HLA-A2, complexed with a common antigenic T cell HLA-A2-restricted epitope derived from the melanoma differentiation Ag gp100. Using a phage display approach, we isolated a recombinant scFv Ab that exhibits a characteristic TCR-like binding specificity, yet, unlike TCRs, it did so with a high affinity in the nanomolar range. The TCR-like Ab can recognize the native MHC-peptide complex expressed on the surface of APCs, and on peptide-pulsed or native melanoma cells. Moreover, when fused to a very potent cytotoxic effector molecule in the form of a truncated bacterial toxin, it was able to specifically kill APCs in a peptide-dependent manner. These results demonstrate the utility of high affinity TRC-like scFv recombinant Abs directed toward human cancer T cell epitopes. Such TCR-like Abs may prove to be very useful for monitoring and visualizing the expression of specific MHC-peptide complexes on the surface of tumor cells, APCs, and lymphoid tissues, as well as for developing a new family of targeting agents for immunotherapy.
AlGaN/GaN two-dimensional-electron gas heterostructures on 200 mm diameter Si(111) (2012)

This Letter reports on the epitaxial growth, characterization, and device characteristics of crack-free AlGaN/GaN heterostructures on a 200 mm diameter Si(111) substrate. The total nitride stack thickness of the sample grown by the metal-organic chemical vapor deposition technique is about 3.3 ± 0.1 μm. The structural and optical properties of these layers are studied by cross-sectional scanning transmission electron microscopy, high-resolution x-ray diffraction, photoluminescence, and micro-Raman spectroscopy techniques. The top AlGaN/GaN heterointerfaces reveal the formation of a two-dimensional electron gas with average Hall mobility values in the range of 1800 to 1900 cm2/Vs across such 200 mm diameter GaN on Si(111) samples. The fabricated 1.5 μm-gate AlGaN/GaN high-electron-mobility transistors exhibited the drain current density of 660 mA/mm and extrinsic transconductance of 210 mS/mm. These experimental results show immense potential of 200-mm diameter GaN-on-silicon technology for electronic device applications.
Regulation of sterol regulatory element-binding proteins by cholesterol flux in CaCo-2 cells (2001)

The regulation of sterol regulatory element-binding proteins (SREBP) by cholesterol flux was studied in the intestinal cell line CaCo-2. CaCo-2 cells were incubated for 18 h with micelles containing 5 mM taurocholate and 500 microM oleic acid or micelles containing either 200 microM cholesterol or 150 microM lysophosphatidylcholine. In some incubations, an ACAT inhibitor was added or 25-hydroxycholesterol was substituted for cholesterol. The SREBP-1a transcript was 2-fold more abundant than the SREBP-1c transcript. In cells incubated with micelles containing cholesterol, rates of cholesterol synthesis were decreased and rates of esterification were increased. Cholesterol synthesis was decreased further by ACAT inhibition. Cholesterol influx decreased mRNA levels of SREBP-2, HMG-CoA synthase, HMG-CoA reductase, and fatty acid synthase. ACAT inhibition modestly suppressed gene expression further. Neither SREBP-1a nor SREBP-1c mRNA levels were altered by cholesterol. Despite decreases in gene expression of the sterol-responsive genes by cholesterol, the amounts of precursor and mature forms of SREBP-1 and SREBP-2 were not altered. In contrast, if 25-hydroxycholesterol was substituted for cholesterol, both the precursor and mature forms of SREBP-2 were decreased. The polar sterol decreased the mature form of SREBP-1 but the amount of the precursor form was unchanged. In cells incubated with micelles containing lysophosphatidylcholine, which causes cholesterol to efflux from cells, sterol-responsive gene expression was increased. The amounts of precursor and mature forms of SREBP-1 and SREBP-2, however, were not altered. In contrast, if the cells were depleted of cholesterol by incubating them with lovastatin and cyclodextrin, the mature forms of SREBP-1 and SREBP-2 were increased, as were mRNA levels for the sterol-responsive genes. The data would suggest that cholesterol influx/efflux regulates mRNA levels of sterol-responsive genes independently of changes in the amount of mature SREBP. In contrast, 25-hydroxycholesterol influx or cholesterol depletion alters the amount of mature SREBP, leading to the regulation of sterol-responsive gene expression.
Genome-wide methylation and transcriptome analysis in penile carcinoma: uncovering new molecular markers (2015)

A unique methylome signature was found for PeCa compared to SNT, with aberrant DNA methylation appearing to modulate the expression of specific genes. This study describes new pathways with the potential to regulate penile carcinogenesis, including stem cell regulatory pathways and markers associated to a worse prognosis. These findings may be instrumental in the discovery and application of new genetic and epigenetic biomarkers in PeCa.
The Biologic Concept of Continuous Passive Motion of Synovial Joints (1989)

The notoriously limited capacity of articular cartilage to heal or to regenerate plus the author's clinical observations and research on the deleterious effects of immobilization on joints led him to the biologic concept of continuous passive motion (CPM) of synovial joints in 1970. The hypothesis that CPM should stimulate pluripotential mesenchymal cells to differentiate into articular cartilage and should accelerate the healing of articular tissues has been validated by numerous scientific investigations of a variety of experimental models of the knee joint. These models have included full-thickness defects, intraarticular fractures, acute septic arthritis, partial thickness lacerations of the patellar tendon, semitendinosus tenodesis to replace the medial collateral ligament, autogeneic osteoperiosteal grafts in major defects, free autogeneic periosteal grafts, and periosteal allografts. In 1978, the author collaborated with Saringer, an engineer, to develop CPM devices for humans. CPM is clinically indicated following such procedures as open reduction of fractures, arthrolysis for posttraumatic arthritis, synovectomy, drainage of septic arthritis, release of joint contractures, total arthroplasty, tendon repair, and ligament reconstruction. Clinically, CPM is an important stimulus to joint regeneration processes.
Early events of in-vitro fertilization of cat eggs by epididymal spermatozoa (1985)

Newly ovulated eggs from mature queens treated with PMSG and hCG were inseminated in modified KRB solution with spermatozoa recovered from the cauda epididymidis of male cats. When 5 eggs were examined 15 min after insemination, no signs of sperm penetration into the vitellus were observed. However, in an egg examined before fixation 20 min after insemination, a spermatozoon whose head had passed through the zona pellucida was observed. Very high proportions (90-100%) of the eggs were penetrated when they were examined 0.5-5 h after insemination. Male and female pronuclei were first observed in eggs examined 4 h after insemination.
Upregulation of class I major histocompatibility complex antigens by interferon gamma is necessary for T-cell-mediated elimination of recombinant adenovirus-infected hepatocytes in vivo. (1995)

Recombinant adenoviruses are attractive vehicles for liver-directed gene therapy because of the high efficiency with which they transfer genes to hepatocytes in vivo. First generation recombinant adenoviruses deleted of E1 sequences also express recombinant and early and late viral genes, which lead to development of destructive cellular immune responses. Previous studies indicated that class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTLs) play a major role in eliminating virus-infected cells. The present studies utilize mouse models to evaluate the role of T-helper cells in the primary response to adenovirus-mediated gene transfer to the liver. In vivo ablation of CD4+ cells or interferon gamma (IFN-gamma) was sufficient to prevent the elimination of adenovirus-transduced hepatocytes, despite the induction of a measurable CTL response. Mobilization of an effective TH1 response as measured by in vitro proliferation assays was associated with substantial upregulation of MHC class I expression, an effect that was prevented in IFN-gamma-deficient animals. These results suggest that elimination of virus-infected hepatocytes in a primary exposure to recombinant adenovirus requires both induction of antigen-specific CTLs as well as sensitization of the target cell by TH1-mediated activation of MHC class I expression.
Noninjectable methods of insulin administration (2006)

Optimal glycemic control is essential for the prevention of diabetes-related complications, and the intensive insulin regimens that best resemble physiological insulin secretion are most likely to attain it. However, there are many limitations that preclude the early use of insulin by patients with type 2 diabetes or wider implementation of the intensive regimens in type 1 diabetes. More acceptable alternative routes of insulin administration and effective, noninvasive, patient-friendly delivery systems that alleviate the burden of insulin injections have been researched over the years. To date, only pulmonary inhalation of insulin has become a feasible alternative; it has proved to be as effective and well tolerated as the subcutaneously injected regular insulin and it has a pharmacodynamic profile well suited for mealtime insulin therapy. Several pulmonary insulin delivery systems are in different stages of development, and one (Exubera, Nektar Therapeutics/Pfizer Inc.-Sanofi-Aventis Group) has already become clinically available in the United States and Europe for patients with diabetes. Other noninjectable methods of insulin administration are reviewed.
Current and Future Directions in Applied Mathematics (1997)

With very tight funding in pure mathematics, it has become increasingly necessary for mathematicians to address the question of what applications their work has in the real world of engineering and science. This text discusses the types of problems that are of current interest and provides some guidelines for mathematicians, both professional and graduate students, as to where their efforts could best be placed.
Crystal Structure of the Tyrosine Kinase Domain of Colony-stimulating Factor-1 Receptor (cFMS) in Complex with Two Inhibitors (2006)

The cFMS proto-oncogene encodes for the colony-stimulating factor-1 receptor, a receptor-tyrosine kinase responsible for the differentiation and maturation of certain macrophages. Upon binding its ligand colony-stimulating factor-1 cFMS autophosphorylates, dimerizes, and induces phosphorylation of downstream targets. We report the novel crystal structure of unphosphorylated cFMS in complex with two members of different classes of drug-like protein kinase inhibitors. cFMS exhibits a typical bi-lobal kinase fold, and its activation loop and DFG motif are found to be in the canonical inactive conformation. Both ATP competitive inhibitors are bound in the active site and demonstrate a binding mode similar to that of STI-571 bound to cABL. The DFG motif is prevented from switching into the catalytically competent conformation through interactions with the inhibitors. Activation of cFMS is also inhibited by the juxtamembrane domain, which interacts with residues of the active site and prevents formation of the activated kinase. Together the structures of cFMS provide further insight into the autoinhibition of receptor-tyrosine kinases via their respective juxtamembrane domains; additionally the binding mode of two novel classes of kinase inhibitors will guide the design of novel molecules targeting macrophage-related diseases.
Robust location using system dynamics and motion constraints (2004)

To our knowledge, the indoor location system which currently achieves the best performance using inexpensive off-the-shelf equipment locates a mobile within 1.5 meters with probability 77% in hallways. Even while maintaining this accuracy, the system often reports logical errors such as the mobile in the wrong cubicle of an office or even on the wrong side of a wall when broadening the domain of application to within rooms. We propose an extension of the work using the same Markov localization framework, however incorporating system dynamics (necessitating no post-processing of the output) and motion constraints which implicitly encode the physical properties of the survey area. Our system retains the advantages of its predecessor of low cost, wireless LAN connectivity and security, and large-scale deployment, however extending the survey area from simple hallways to the whole office environment, while maintaining the same precision without logical errors.