gebhart/patrepeval huggingface dataset:
TiNivo - tivozanib combined with nivolumab: Safety and efficacy in patients with metastatic renal cell carcinoma (mRCC) (2018)

Background: Recently approved in the EU, tivozanib is a VEGFR-TKI with high specificity and lower incidence of class effect adverse events. We reported earlier that tivozanib can be combined with nivolumab at full dose of each drug. We report herein safety and efficacy data from a phase Ib/II combination of tivozanib and nivolumab. Methods: In the phase Ib portion of the study, tivozanib was administered orally at 1.0 mg and 1.5 mg, once daily for 21 days every 28 day cycle using a standard 3 + 3 dose escalation design in combination with nivolumab 240 mg every 14 days intravenously. As there were no DLTs in phase I, in the phase II portion of the study tivozanib was administered orally at 1.5 mg in combination with nivolumab. Results: 28 patients have been enrolled, 6 in phase Ib and 22 in phase II. 25 were treated with full dose tivozanib, 1.5 mg daily for 21 days with nivolumab. The median age was 63; 8 patients were IMDC favorable; 19 IMDC intermediate; 1 IMDC poor. 18 patients were ECOG 0 and 9 ECOG 1; and there were 20 males. 24 had clear cell histology. All patients experienced at least one AE and 52% experienced a grade 3/4 AE. 44% experienced a grade 3/4 AE related to study drug. The most common grade 3/4 adverse events were hypertension, hand foot syndrome, and elevated lipase seen in 4, 2 and 2 patients respectively. The most common AEs (all grades) were hypertension, asthenia, arthralgia, dysphonia, mucocitis, diarrhea, and anorexia. 9 of the first 14 patients (64%) enrolled and treated with full dose tivozanib had a partial response. Final efficacy and safety data on all 28 patients will be available at the meeting. Conclusions: The combination of tivozanib with nivolumab is safe and manageable at full dose of both drugs. The safety profile and the activity is favorable for a combination of a TKI with a checkpoint inhibitor as would be expected for a highly selective and well tolerated TKI. Clinical trial identification: NCT03136627. Legal entity responsible for the study: Aveo Oncology. Funding: Aveo Oncology; Bristol Myers Squibb. Disclosure: P. Barthelemy: Consulting relationship: BMS, Novartis, Pfizer, Roche, MSD; Honoraria: Janssen Cilag, Sanofi, Astellas. B. Escudier: Honorarium: Pfizer, Novartis, BMS, Roche, Ipsen, EUSA. A. Ravaud: Member of advisory boards in RCC: Pfizer, Novartis, BMS, Ipsen, Roche; Travel support for meetings or speeches: Pfizer, Novartis, BMS, Ipsen, Roche, AstraZeneca. S. Negrier: Honoraria: Pfizer, Ipsen, BMS, EUSA Pharma, Novartis; Research grant: Pfizer; Travel expenses: BMS, Pfizer, Ipsen. M.N. Needle: Full time employee, officer and shareholder: Aveo Oncology. L. Albiges: Consulting: Bristol-Myers Squibb, Pfizer, Novartis, Ipsen, Roche, Astellas Pharma, Merck, Amgen.
Direct measurement of soluble CD4 binding to human immunodeficiency virus type 1 virions: gp120 dissociation and its implications for virus-cell binding and fusion reactions and their neutralization by soluble CD4 (1991)

We have analyzed the binding of soluble CD4 (sCD4) to human immunodeficiency virus type 1 (HIV-1) virions (isolates IIIB and RF) at 4 and 37 degrees C by using a combination of gel exclusion chromatography and enzyme-linked immunosorbent assay detection systems. The sCD4 binding curve at 37 degrees C indicates that the affinity of the interaction of sCD4 with gp120 on the virion surface is indistinguishable from the affinity of sCD4 for the equivalent concentration of soluble gp120. At 4 degrees C, however, the affinity of sCD4 for virion-bound gp120 but not for soluble gp120 is reduced by about 20-fold. Binding of sCD4 (greater than 0.2 microgram/ml) to virions at 37 degrees C but not 4 degrees C induces the rapid dissociation of a major proportion of gp120 from gp41 on the virion surface. This dissociation requires occupancy by sCD4 of multiple (probably two) binding sites on a gp120-gp41 oligomer. At 37 degrees C there are two components to the neutralizing action of sCD4 on HIV-1; reversible, competitive inhibition at low sCD4 concentrations (less than 0.2 microgram/ml) and essentially irreversible inhibition due to gp120 loss at higher sCD4 concentrations. At 4 degrees C, sCD4 neutralizes HIV infectivity by competitive inhibition alone. These findings may have implications for the HIV-CD4+ cell binding and fusion reactions and the mechanism by which sCD4 blocks infectivity.
Sham Surgery and Genuine Standards of Care: Can the Two be Reconciled? (2003)

Department of Philosophy technical report
A fast-settling CMOS op amp for SC circuits with 90-dB DC gain (1990)

A technique that combines the high-frequency behavior of a single-stage op amp with the high DC gain of a multistage design is presented. This technique is based on the concept that a very high DC gain can be achieved in combination with any unity-gain frequency achievable by a (folded-) cascode design. Bode-plot measurements for an op amp realized in a 1.6- mu m process show a DC gain of 90 dB and a unity-gain frequency of 116 MHz (16-pF load). Settling measurements with a feedback factor of 1/3 show a fast single-pole settling behavior corresponding to a closed-loop bandwidth of 18 MHz (35-pF load) and a settling accuracy better than 0.03%. This technique does not cause any loss in output voltage swing. At a supply voltage of 5.0 V an output swing of about 4.2 V is achieved without loss in DC gain. The above advantages are achieved with a 30% increase in chip area and a 15% increase in power consumption.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Uniform Service Description and Contextual Access Control for Trustworthy Cloud Computing (2018)

Cloud Computing (CC) is a paradigm of providing services to a variety of clients, individuals, and organizations, through a large-scale distributed computing environment. It is a shared pool of resources that are dynamically configured to meet demands and provide reliable and rapid services, with minimal management required from the clients. The number of enterprises and individuals using both public and private CC services is steadily increasing, yet there is a deep concern about the security risks of embedding their assets in cloud. Research on CC security has only revealed the necessity to improve security, with no consensus yet on a sound methodology at CC level for achieving a satisfactory level of trust of CC clients. This paper contributes to this area of research by offering two proposals. The first proposal is a uniform CC service model to earn trust of clients. The second proposal is the application of Context-sensitive Role-Based Access Control (CRBAC) method for establishing identity, and enforcing security and privacy in CC service transactions.
The YAGS branch prediction scheme (2002)

The importance of an accurate branch prediction mechanism has been well documented. Since the introduction of gshare and the observation that aliasing in the PHT is a major factor in reducing prediction accuracy, several schemes have been proposed to reduce aliasing in the PHT. All these schemes are aimed at maximizing the prediction accuracy with the fewest resources. In this paper we introduce Yet Another Global Scheme (YAGS)-a new scheme to reduce the aliasing in the PHT-that combines the strong points of several previous schemes. YAGS introduces tags into the PHT that allows it to be reduced without sacrificing key branch outcome information. The size reduction more than offsets the cost of the tags. Our experimental results show that YAGS gives better prediction accuracy for the SPEC95 benchmark suite than several leading prediction schemes, for the same cost. It also performs better than the other schemes in the presence of a context switch. Finally, YAGS displays good results for the go benchmark, which is of special interest since it has a large number of static branches and reflects situations where aliasing in the PHT can be a problem.
Influence of stress on light-induced effects in amorphous silicon alloys (1985)

We have studied the effect of stress on light-induced changes in photoconductivity and solar cell performance of amorphous silicon alloys. We find no correlation between degradation and stress in the material.
A parallel‐series‐fed microstrip array with high efficiency and low cross‐polarization (1992)

Abstract A linearly polarized traveling‐wave microstrip array antenna is parallel and series fed by microstrip transmission lines. Excellent antenna efficiency is achieved by having proper impedance matching throughout the array and by properly utilizing the reflected power from the end of the array. Very low cross‐polarization radiation is achieved by exciting the patches and transmission lines with antiphase technique.
Autologous Platelet-Rich Plasma Promotes Neurogenic Differentiation of Human Adipose-Derived Stem Cells in vitro (2012)

Nervous system injury causes severe medical and social problems worldwide, and doctors have not found any ultimate solutions to it until now. The regenerative medicine using stem cells is a promising technology to conquer this challenge. In this study, we explored the influence of platelet-rich plasma (PRP) on neural differentiation of adipose-derived stem cells (ASCs). Human ASCs (hASCs) were harvested and isolated from lipoaspirates of liposuction operations. They were cultured to the third passage and characterized by specific cell markers and multilineage differentiation capacities. Autologous PRP was isolated and prepared from venous blood of the same patient underwent liposuction. The cultured hASCs were treated with either neural inductive conditioned medium plus 10% PRP (experimental group) or neural inductive conditioned medium alone (control group). The supplement of autologous PRP into culture medium obviously promoted proliferation of hASCs. After two weeks of neurogenic induction, the hASCs treated with PRP displayed higher level of neuron-specific enolase and membrane-associated protein-2 compared with the control group. Gene expression level of growth associated protein-43 (GAP-43), neural cell adhesion molecule (NCAM), and synapsin 1 (SYN-1) in the PRP group was also higher than in the control group. These results indicate PRP is capable of promoting cell proliferation and neurogenic differentiation of hASCs in vitro. Addition of autologous PRP could facilitate the potential use of hASCs in nerve regeneration.
Naturally Occurring Baculoviruses for Insect Pest Control (2003)

Baculoviruses of insects have been promoted for their pest control potential forinore than half a century (). Despite this, only a few have been successful in biological control, and almost none has proven a commercial success, or is used routinely for large-scale Insect controlin industrialtied countries Baculoviruses have, however, achievedinoderate success in some developing countries. Thus, in addition to discussing the use of naturally occurring baculoviruses as pest-control agents, the reasons why these viruses have not been of greater commercial success in industrialized countries will be considered. This requires definition of both the different ways baculoviruses can be used for insect control, and the performance expectations used to evaluate baculovirus success. Such an assessment identifies the key features required for a virus to be successful as a control agent. Though baculoviruses are used as the examples here, these principles apply to other pathogens, and many predators and parasites, as well.
γ-Tubulin complexes in microtubule nucleation and beyond (2015)

Tremendous progress has been made in understanding the functions of γ-tubulin and, in particular, its role in microtubule nucleation since the publication of its discovery in 1989. The structure of γ-tubulin has been determined, and the components of γ-tubulin complexes have been identified. Significant progress in understanding the structure of the γ-tubulin ring complex and its components has led to a persuasive model for how these complexes nucleate microtubule assembly. At the same time, data have accumulated that γ-tubulin has important but less well understood functions that are not simply a consequence of its function in microtubule nucleation. These include roles in the regulation of plus-end microtubule dynamics, gene regulation, and mitotic and cell cycle regulation. Finally, evidence is emerging that γ-tubulin mutations or alterations of γ-tubulin expression play an important role in certain types of cancer and in other diseases.
Pseudo-quaternary GaInAsP semiconductors: A new Ga0.47In0.53As/InP graded gap superlattice and its applications to avalanche photodiodes (1984)

We have demonstrated for the first time a pseudo-quaternary GaInAsP semiconductor consisting of a graded gap Ga0.47In0.53As/InP superlattice. The average composition and the band gap of this structure are spatially varied by gradually changing the thicknesses of the InP and Ga0.47In0.53As layers between 5 and 55 Å while keeping constant the period of the superlattice (=60 Å). This new graded gap superlattice has been used to eliminate the interface pile-up effect of holes in a ‘‘high-low’’ InP/Ga0.47In0.53As avalanche photodiode, without requiring the growth of a separately lattice-matched Ga1−xInxAs1−yPy layer. High-speed operation at 1.7 Gb/s and λ=1.55 μm has been achieved. Pseudo-quaternary semiconductors represent a new technique of growing GaInAsP and can conveniently replace conventional Ga1−xInxAs1−yPy alloys in a variety of device applications.
Methionine catabolism in <i>Arabidopsis</i> cells is initiated by a γ-cleavage process and leads to <i>S</i> -methylcysteine and isoleucine syntheses (2006)

Despite recent progress in elucidating the regulation of methionine (Met) synthesis, little is known about the catabolism of this amino acid in plants. In this article, we present several lines of evidence indicating that the cleavage of Met catalyzed by Met gamma-lyase is the first step in this process. First, we cloned an Arabidopsis cDNA coding a functional Met gamma-lyase (AtMGL), a cytosolic enzyme catalyzing the conversion of Met into methanethiol, alpha-ketobutyrate, and ammonia. AtMGL is present in all of the Arabidopsis organs and tissues analyzed, except in quiescent dry mature seeds, thus suggesting that AtMGL is involved in the regulation of Met homeostasis in various situations. Also, we demonstrated that the expression of AtMGL was induced in Arabidopsis cells in response to high Met levels, probably to bypass the elevated Km of the enzyme for Met. Second, [13C]-NMR profiling of Arabidopsis cells fed with [13C]Met allowed us to identify labeled S-adenosylmethionine, S-methylmethionine, S-methylcysteine (SMC), and isoleucine (Ile). The unexpected production of SMC and Ile was directly associated to the function of Met gamma-lyase. Indeed, we showed that part of the methanethiol produced during Met cleavage could react with an activated form of serine to produce SMC. The second product of Met cleavage, alpha-ketobutyrate, entered the pathway of Ile synthesis in plastids. Together, these data indicate that Met catabolism in Arabidopsis cells is initiated by a gamma-cleavage process and can result in the formation of the essential amino acid Ile and a potential storage form for sulfide or methyl groups, SMC.
A luminous efficiency function,<i>V</i>*(<i>λ</i>), for daylight adaptation (2005)

We propose a new luminosity function, V*(lambda), that improves upon the original CIE 1924 V(lambda) function and its modification by D. B. Judd (1951) and J. J. Vos (1978), while being consistent with a linear combination of the A. Stockman & L. T. Sharpe (2000) long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cone fundamentals. It is based on experimentally determined 25 Hz, 2 degrees diameter, heterochromatic (minimum) flicker photometric data obtained from 40 observers (35 males, 5 females) of known genotype, 22 with the serine variant L(ser180), 16 with the alanine L(ala180) variant, and 2 with both variants of the L-cone photopigment. The matches, from 425 to 675 nm in 5-nm steps, were made on a 3 log troland xenon white (correlated color temperature of 5586 K but tritanopically metameric with CIE D65 standard daylight for the Stockman and Sharpe L- and M-cone fundamentals in quantal units) adapting field of 16 degrees angular subtense, relative to a 560-nm standard. Both the reference standard and test lights were kept near flicker threshold so that, in the region of the targets, the total retinal illuminance averaged 3.19 log trolands. The advantages of the new function are as follows: it forms a consistent set with the new proposed CIE cone fundamentals (which are the Stockman & Sharpe 2000 cone fundamentals); it is based solely on flicker photometry, which is the standard method for defining luminance; it corresponds to a central 2 degrees viewing field, for which the basic laws of brightness matching are valid for flicker photometry; its composition of the serine/alanine L-cone pigment polymorphism (58:42) closely matches the reported incidence in the normal population (56:44; Stockman & Sharpe, 1999); and it specifies luminance for a reproducible, standard daylight condition. V*(lambda) is defined as 1.55L(lambda) + M(lambda), where L(lambda) and M(lambda) are the Stockman & Sharpe L- & M-cone (quantal) fundamentals. It is extrapolated to wavelengths shorter than 425 nm and longer than 675 nm using the Stockman & Sharpe cone fundamentals.
Skeletal Muscle Cell Behavior After Physical Agent Treatments (2015)

Apoptosis is essential for skeletal muscle development and homeostasis. It has been frequently involved in several muscle myopathies and sarcopenia, as well as in denervation, in disuse and acute strenuous or eccentric physical exercise. In this work skeletal muscle cell death, induced in vitro by a variety of physical triggers, has been investigated. C2C12 myoblasts and myotubes were exposed to UVB for 30 min, hyperthermia for 1 h at 43 °C, low pH for 3 h, hypothermia for 4h at 0 - 6°C, all followed by 2 - 4 h recovery. Their effects have been analysed by means of morpho- functional and molecular approaches. After UVB radiation, hyperthermia and acidosis, morphological apoptotic features and in situ DNA fragmentation appeared, more evident in myoblasts. Interestingly, apoptotic, non apoptotic and necrotic nuclei could be occasionally observed within the same myotube. Low pH induced apoptosis and necrosis, both characterized by swollen nuclei. In all these experimental conditions, the molecular investigations revealed a caspase pathway involvement in inducing cell death. Differently, hypothermia showed a scant and initial chromatin margination, in the presence of a diffused autophagic component. In this case, in situ DNA fragmentation and caspase activation have not been detected. Myoblasts and myotubes appeared sensitive to physical agents, some of which, induced apoptotic cell death. Moreover, hypothermia exposure seemed to enhance autophagic response, thus representing a way to delay trauma-correlated muscle inflammation. This study permits to highlight skeletal muscle cell behavior in response to physical agents, by adding important information to muscle cell death knowledge. UVB radiation and hyperthermia, usually used in clinical therapy, have also adverse effects on skeletal muscle such as myonuclei loss and cell death, contributing to muscle mass decrease. Acidosis occurs physiologically in muscular fatigue, reducing not only the athlete performance, but causing muscle cell damage or death too. Finally, hypothermia, stimulating the autophagic response, could have a key role in muscle injury prevention.
The monoblocking of symmetrical diketones on insoluble polymer supports (1983)

A 1% crosslinked divinylbenzene–styrene copolymer, incorporating vicinal diol groups or their isopropylidenc precursors, was used to form the monoacetals of the symmetrical diketones, p-diacetylbenzene, 1,2-cyclohexanedione, 1,3-cyclohexanedionc, 1,4-cyclohexanedione, and 2,5-hexanedione. The free ketone groups reacted with phenylmagnesium bromide to give, in high yield, after acid hydrolysis from the polymer, the expected products such as 3-phenyl-2-cyclohexen-1-one from 1,3-cyclohexanedione. The 13 C nmr spectra of some polymer-bound substrates and simple analogs are described.
Characterization of a corrinoid protein involved in the C1 metabolism of strict anaerobic bacterium <i>Moorella thermoacetica</i> (2007)

The strict anaerobic, thermophilic bacterium Moorella thermoacetica metabolizes C1 compounds for example CO(2)/H(2), CO, formate, and methanol into acetate via the Wood/Ljungdahl pathway. Some of the key steps in this pathway include the metabolism of the C1 compounds into the methyl group of methylenetetrahydrofolate (MTHF) and the transfer of the methyl group from MTHF to the methyl group of acetyl-CoA catalyzed by methyltransferase, corrinoid protein and CO dehydrogenase/acetyl CoA synthase. Recently, we reported the crystallization of a 25 kDa methanol-induced corrinoid protein from M. thermoacetica (Zhou et al., Acta Crystallogr F 2005; 61:537-540). In this study we analyzed the crystal structure of the 25 kDa protein and provide genetic and biochemical evidences supporting its role in the methanol metabolism of M. thermoacetia. The 25 kDa protein was encoded by orf1948 of contig 303 in the M. thermoacetica genome. It resembles similarity to MtaC the corrinoid protein of the methanol:CoM methyltransferase system of methane producing archaea. The latter enzyme system also contains two additional enzymes MtaA and MtaB. Homologs of MtaA and MtaB were found to be encoded by orf2632 of contig 303 and orf1949 of contig 309, respectively, in the M. thermoacetica genome. The orf1948 and orf1949 were co-transcribed from a single polycistronic operon. Metal analysis and spectroscopic data confirmed the presence of cobalt and the corrinoid in the purified 25 kDa protein. High resolution X-ray crystal structure of the purified 25 kDa protein revealed corrinoid as methylcobalamin with the imidazole of histidine as the alpha-axial ligand replacing benziimidazole, suggesting base-off configuration for the corrinoid. Methanol significantly activated the expression of the 25 kDa protein. Cyanide and nitrate inhibited methanol metabolism and suppressed the level of the 25 kDa protein. The results suggest a role of the 25 kDa protein in the methanol metabolism of M. thermoacetica.
The Frequency Dependence of Osmo-Adaptation in <i>Saccharomyces cerevisiae</i> (2008)

The propagation of information through signaling cascades spans a wide range of time scales, including the rapid ligand-receptor interaction and the much slower response of downstream gene expression. To determine which dynamic range dominates a response, we used periodic stimuli to measure the frequency dependence of signal transduction in the osmo-adaptation pathway of Saccharomyces cerevisiae. We applied system identification methods to infer a concise predictive model. We found that the dynamics of the osmo-adaptation response are dominated by a fast-acting negative feedback through the kinase Hog1 that does not require protein synthesis. After large osmotic shocks, an additional, much slower, negative feedback through gene expression allows cells to respond faster to future stimuli.
Predicting final infarct size using acute and subacute multiparametric MRI measurements in patients with ischemic stroke (2005)

Acute-phase DWI and DWI-ISODATA mismatch strongly predict the final infarct size. An acute-to-subacute DWI lesion size change further increases the predictive ability of the model.