gebhart/patrepeval huggingface dataset:
Polyindolinic Alkaloids fromPsychotria forsteriana. Potent Inhibitors of the Aggregation of Human Platelets (1985)

Quadrigemine B, quadrigemine A, isopsychotridine C and psychotridine, isolated from PSYCHOTRIA FORSTERIANA, are potent inhibitors of the aggregation of washed human platelets induced by ADP, collagen or thrombin. The four compounds are active in the 1-10 microM range. The quadrigemine-type alkaloids do not increase the level of platelet cyclic AMP, either alone or in the presence of 20 nM prostaglandin E, (PGE (1)), an activator of adenylate cyclase. The characteristics of the pharmacological action of these compounds suggest that they act at a later stage in platelet activation, possibly through an interaction with cytoskeletal proteins.
Amelioration of Chronic Murine Colitis by Peptide-Mediated Transduction of the IκB Kinase Inhibitor NEMO Binding Domain Peptide (2007)

The NF-kappaB family of transcription factors is a central regulator of chronic inflammation. The phosphorylation of IkappaB proteins by the IkappaB kinase (IKK) complex (IKKalpha, IKKbeta, and NF-kappaB essential modulator or NEMO) is a key step in NF-kappaB activation. Peptides corresponding to the NEMO binding domain (NBD) of IKK blocks NF-kappaB activation without inhibiting basal NF-kappaB activity. In this report, we determined the effects of the IKK inhibitor peptide (NBD) in a model of spontaneously occurring chronic murine colitis, the IL-10-deficient (IL-10(-/-)) mouse. Using a novel cationic peptide transduction domain (PTD) consisting of eight lysine residues (8K), we were able to transduce the NBD peptide into cells and tissues. In a NF-kappaB reporter system, 8K-NBD dose-dependently inhibits TNF-induced NF-kappaB activation. Furthermore, 8K-NBD inhibited nuclear translocation of NF-kappaB family members. In NF-kappaB(EGFP) knock-in mice, 8K-NBD inhibited LPS-activated NF-kappaB (EGFP activity) in the ileum but did not inhibit basal NF-kappaB in Peyer's patches. IL-10(-/-) mice treated systemically with 8K-NBD demonstrate amelioration of established colitis, decreased NF-kappaB activation in the lamina propria, and a reduction in spontaneous intestinal IL-12 p40, TNF, IFN-gamma, and IL-17 production. These results demonstrate that inhibitors of IKK, in particular a PTD-NBD peptide, may be therapeutic in the treatment of inflammatory bowel disease.
Lottery scheduling: flexible proportional-share resource management (1994)

This paper presents lottery scheduling, a novel randomized resource allocation mechanism. Lottery scheduling provides efficient, responsive control over the relative execution rates of computations. Such control is beyond the capabilities of conventional schedulers, and is desirable in systems that service requests of varying importance, such as databases, media-based applications, and networks. Lottery scheduling also supports modular resource management by enabling concurrent modules to insulate their resource allocation policies from one another. A currency abstraction is introduced to flexibly name, share, and protect resource rights. We also show that lottery scheduling can be generalized to manage many diverse resources, such as I/O bandwidth, memory, and access to locks. We have implemented a prototype lottery scheduler for the Mach 3.0 microkernel, and found that it provides flexible and responsive control over the relative execution rates of a wide range of applications. The overhead imposed by our unoptimized prototype is comparable to that of the standard Mach timesharing policy.
Regulation of Dendritic Cell Differentiation and Antitumor Immune Response in Cancer by Pharmacologic-Selective Inhibition of the Janus-Activated Kinase 2/Signal Transducers and Activators of Transcription 3 Pathway (2005)

Abnormal dendritic cell differentiation and accumulation of immunosuppressive myeloid cells in cancer is one of the major factors of tumor nonresponsiveness. We have previously shown that hyperactivation of the Janus-activated kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) induced by tumor-derived factors (TDF) is responsible for abnormal dendritic cell differentiation. Here, using a novel selective inhibitor of JAK2/STAT3 JSI-124, we investigated the possibility of pharmacologic regulation of dendritic cell differentiation in cancer. Our experiments in vitro have shown that JSI-124 overcomes the differentiation block induced by TDF and promotes the differentiation of mature dendritic cells and macrophages. JSI-124 significantly reduced the presence of immature myeloid cells in vivo and promoted accumulation of mature dendritic cells. In addition to a direct antitumor effect in several animal models, JSI-124 significantly enhanced the effect of cancer immunotherapy. This indicates that pharmacologic inhibition of the JAK2/STAT3 pathway can be an important new therapeutic strategy to enhance antitumor activity of cancer immunotherapy.
Comparative Pathology of Chickens Experimentally Inoculated with Avian Influenza Viruses of Low and High Pathogenicity (1997)

Pathologic changes and distribution of viral antigen as determined by immunohistochemistry were compared among 4-wk-old specific-pathogen-free chickens inoculated intratracheally with avian influenza virus (AIV) isolates of either low or high pathogenicity. Viruses of low pathogenicity, previously characterized as mildly pathogenic (MP), included A/chicken/Pennsylvania/21525/83 (H5N2) (MP-Penn) and A/chicken/Alabama/7395/75 (H4N8) (MP-Alab). Viruses of high pathogenicity included A/chicken/Pennsylvania/1370/83 (H5N2), A/chicken/Victoria/A185/85 (H7N7), and A/turkey/Ontario/7732/66 (H5N9). Extremely variable clinical signs ranging from mild respiratory distress to high mortality were present among chickens inoculated with these viruses. Chickens inoculated with highly pathogenic (HP) virus had histologic lesions of necrosis and inflammation in cloacal bursa, thymus, spleen, heart, pancreas, kidney, brain, trachea, lung, and skeletal muscle, whereas chickens inoculated with MP virus had histologic lesions most frequently in lung and trachea or lacked histologic lesions. Immunospecific staining for avian influenza viral proteins was most common in cells within heart, lung, kidney, brain, and pancreas of chicken inoculated with HP viruses, but immunospecific staining was present only and infrequently in trachea and lung of chickens inoculated with MP-Penn AIV. MP-Alab did not produce lesions nor have viral antigen in inoculated chickens but did produce serologic evidence of infection. The pattern of organ involvement and viral antigen distribution in chickens intratracheally inoculated with HP AIV isolates indicates a common capability to spread beyond the respiratory tract and confirms the pantrophic replicative, pathobiologic, and lethal nature of the viruses. However, variability in severity and lesion distribution exists between different HP AIVs. By contrast, MP viruses had the ability to replicate in respiratory or enteric tracts or both and produce lesions within the respiratory tract. These MP viruses exhibited a restricted ability to replicate or produce lesions or both in nonrespiratory or nonenteric tissues; such effects were associated with only sporadic deaths.
Neutralizing windows-based malicious mobile code (2002)

Mobile code---executable programs that get copied from computer-to-computer via e-mail, web browsers, etc.---is a popular way to stage malicious attacks against users. The Windows operating system is often the target of such attacks, in part because of its ubiquity and in part because of the vast functionality it provides. Some of this functionality, like executable e-mail attachments and scripting, provides opportunity for mobile code to cause significant damage to a host system. One obvious solution is to disable such features in Windows. However, many users find such features a convenient and productive way to conduct their business. Thus, techniques that can protect against mobile code without sacrificing functionality are needed.But even disabling functionality such as scripting will not provide complete security; it only catches the most sophomoric exploits. All operating systems, including Windows, are vulnerable to malicious use at their lowest level of operation: executing compiled code. Mobile programs, just like local programs, can access operating system components in ways that damage a users' data or render their computer useless. These programs can be written in system-level languages such as C and assembly, which are capable of compiling OS components directly into their binaries and writing directly to interrupt vectors. Disabling such functionality will mean an operating system that simply doesn't work.This paper investigates techniques to protect Windows-based systems from malicious mobile code while minimizing functionality loss. Our solution involves writing a layer of protective code that is able to detect mobile code running on a system and then monitors its behavior. Behaviors deemed benign are allowed to execute; behaviors deemed malicious are either shutdown, quarantined or logged (so that restoration procedures can be constructed). We describe new techniques for identifying. monitoring and neutralizing malicious mobile code. We demonstrate the techniques by testing our "vaccine" against a number of the most notorious Windows viruses and worms. Further, we demonstrate how our solution maintains functionality while minimizing false positives during execution of benign programs.
Comparison of deuterium incorporation and mass isotopomer distribution analysis for measurement of human cholesterol biosynthesis (2000)

To compare endogenous cholesterol biosynthesis measured by deuterium incorporation (DI) and mass isotopomer distribution analysis (MIDA), cholesterol fractional and absolute synthetic rates were measured simultaneously by both techniques under identical physiological conditions. Twelve subjects (22 to 39 years of age) underwent a dual stable isotope protocol, involving oral deuterium oxide administration and measurement of incorporation of deuterium into cholesterol coincident with constant infusion of sodium [1-(13)C]acetate and measurement of the mass isotopomer distribution pattern of newly synthesized cholesterol. Synthesis was determined over 24 h with a 7-h feeding period. Both methods yielded similar measurements of fractional cholesterol synthesis (7.8 +/- 2.5% day(-)(1) for DI vs. 6.9 +/- 2.2% day(-)(1) for MIDA). Correlation of fractional synthesis across techniques was strong (r = 0.84, P = 0.0007). Absolute synthesis rates were also not different at 24 h (13.4 +/- 4.3 mg kg(-)(1) day(-)(1) for DI vs. 11.9 +/- 3.6 mg kg(-)(1) day(-)(1) for MIDA, r = 0.79, P < 0.002). We conclude that despite different assumptions and analytical requirements, deuterium incorporation and MIDA yield similar rates of cholesterogenesis in humans when measurements are made over 24 h. The decision as to which method to adopt depends on available clinical and analytical facilities
Electronic displays (1995)

Electronic displays such as televisions and visual display terminals, use a cathode ray tube that pulsates in brightness, with the top of the display being lit before the bottom repeatedly, at a frequency that can induce seizures. The seizures may be prevented by viewing with one eye using selective polarized occlusion. When text is displayed, the pulsation interferes with saccadic suppression and increases the number of rapid eye movements required for reading.
Sensorless Control of a PMSM Synchronous Motor at Low Speed (2006)

This paper presents a self-sensing technique for a surface-mounted permanent-magnet synchronous machine (SM-PMSM) based on high frequency voltage injection. The reactances of the high frequency model vary as a function of rotor position and a simple method based on measured currents and voltages can be used to identify those reactances. Using the motor reactances, the rotor position and velocity are determined. The proposed technique is relatively independent of the machine parameters and it can be applied to any type of synchronous machine. The proposed technique has been tested experimentally for a commercial SM-PMSM machine. The experimental results have demonstrated the feasibility of the proposed technique
Review of high-speed fiber optic grating sensor systems (2010)

Fiber grating sensors can be used to support a wide variety of high speed measurement applications. This includes measurements of vibrations on bridges, traffic monitoring on freeways, ultrasonic detection to support non-destructive tests on metal plates, and providing details of detonation events. This paper provides a brief overview of some of the techniques that have been used to support high speed measurements using fiber grating sensors over frequency ranges from 10s of kHz, to MHZ and finally toward frequencies approaching the GHz regime.
Recombinant Expression of Lymphocytic Choriomeningitis Virus Strain WE Glycoproteins: a Single Amino Acid Makes the Difference (2001)

Cytoplasmic vector systems are generally used for expression of lymphocytic choriomeningitis virus (LCMV) proteins. However, we achieved high levels of cell surface glycoproteins using a standard nuclear expression plasmid. Expression was independent of other LCMV proteins but was blocked by a missense mutation within the original LCMV(WE) glycoprotein cDNA.
Bone morphogenetic protein induces bone in the squirrel monkey, but bone matrix does not (1992)

Demineralized bone matrix (DBM) reproducibly induces extraskeletal bone formation in rodents, but its effects in dogs and primates are negative or uncertain. In previous studies on the squirrel monkey, DBM did not induce bone, although the same implants were effective in nude rats. In the present study, the DBM was augmented with recombinant human bone morphogenetic protein-2 (BMP-2). Bone was formed in 10 of 12 monkeys, as verified by histology and calcium content. However, in 4 monkeys, the induced bone mass appeared smaller than the original implant. DBM controls induced microscopic amounts of bone in 2 out of 10 monkeys. In the nude rats, all DBM controls and augmented implants induced bone. The difficulties in achieving bone induction in higher animals may be overcome, at least partially, by using a higher concentration of the inductive protein than is present in DBM.
Inferring body pose without tracking body parts (2002)

A novel approach for estimating articulated body posture and motion from monocular video sequences is proposed. Human pose is defined as the instantaneous two dimensional configuration (i.e. the projection onto the image plane) of a single articulated body in terms of the position of a predetermined sets of joints. First, statistical segmentation of the human bodies from the background is performed and low-level visual features are found given the segmented body shape. The goal is to be able to map these generally low level visual features to body configurations. The system estimates different mappings, each one with a specific cluster in the visual feature space. Given a set of body motion sequences for training, unsupervised clustering is obtained via the Expectation Maximization algorithm. For each of the clusters, a function is estimated to build the mapping between low-level features to 2D pose. Given new visual features, a mapping from each cluster is performed to yield a set of possible poses. From this set, the system selects the most likely pose given the learned probability distribution and the visual feature of the proposed approach is characterized using real and artificially generated body postures, showing promising results.
628. Polyamides containing carbohydrate residues. Part II. Benzylidenedioxy-derivatives (1963)

T. P. Bird, W. A. P. Black, E. T. Dewar and J. B. Hare, J. Chem. Soc., 1963, 3389 DOI: 10.1039/JR9630003389
Adjuvant Effect of Nonionic Block Polymer Surfactants in Humoral and Cellular Immunity (1981)

The adjuvant activities of four chemically similar, but physicochemically different nonionic surface-active agents called pluronic polyols F 68, L 31, L 101 and L 121 were studied. These four agents were tested in mice using an experimental model developed for studying the adjuvant activity of the cationic surface-active agent dimethyl dioctadecyl ammonium bromide (DDA). L 121 and DDA enhanced the primary antibody response to sheep red blood cells (SRBC) while F 68, L 31 and L 101 suppressed this response. The secondary humoral response to SRBC was enhanced by the polyol L 121 while the secondary response to dinitrophenylated bovine serum albumin (DNP22-BSA) was enhanced by both L 121 and L 101. DDA and the polyol L 101 were very effective adjuvants for induction of delayed-type hypersensitivity (DTH) to SRBC and DNP22-BSA after intracutaneous immunization of mice with a mixture of antigen and adjuvant. Since the four pluronic polyols were composed of identical chemical constituents, we proposed that difference in their activities as adjuvants were due to variation in their physicochemical properties. A correlation was found between a physicochemical parameter, the hydrophilelipophile balance (HLB), and the adjuvant activities of the pluronic polyols and several other types of nonionic surface-active agents. The agents which were strong adjuvants all had HLB values within a narrow range which classified them as spreading agents.
Targeting of HER2-Expressing Tumors with a Site-Specifically 99mTc-Labeled Recombinant Affibody Molecule, ZHER2:2395, with C-Terminally Engineered Cysteine (2009)

The Affibody molecule (99m)Tc-Z(HER2:2395)-Cys is a promising tracer for SPECT visualization of HER2-expressing tumors.
Melanin-Concentrating Hormone (MCH) Involvement in Pentylenetetrazole (PTZ)-Induced Seizure in Rat and Guinea Pig (1997)

Intraperitoneal injection of 60 mg/kg of pentylenetetrazole (PTZ) induced seizure in rats, but was subthreshold and did not result in seizure in guinea pigs. Three days after intracerebroventricular (i.c.v.) injection of 75 micrograms 6-hydroxydopamine (6-OHDA) in guinea pigs, PTZ induced seizures similar to those seen in rats. In both rats and 6-OHDA-treated guinea pigs, i.c.v. injection of melanin-concentrating hormone (MCH) 15 min before PTZ prevented seizure activity. These results suggest that MCH-containing neurons may participate in the neural circuits involved in expression of PTZ-induced seizure.
ADP-ribosylation factor is functionally and physically associated with the Golgi complex. (1990)

ADP-ribosylation factor (ARF) is a ubiquitous, highly conserved 21-kDa GTP-binding protein, first identified in animal cells as the cofactor required for the in vitro ADP-ribosylation of the stimulatory regulatory subunit of adenylate cyclase, Gs, by cholera toxin. As the relevance of this activity to in vivo function is unknown, we have taken advantage of the conserved nature of ARF to study its function in Saccharomyces cerevisiae. Yeast cells bearing an arf1 null mutation display a number of phenotypes suggesting a defect in the secretory pathway. Secreted invertase is only partially glycosylated, and there is a small internal accumulation of invertase. Genetic experiments revealed interactions between ARF1 and other genes known to be involved in the secretory pathway, including YPT1, which encodes a different GTP-binding protein. In accord with these genetic results, immunofluorescence and immunoelectron microscopy show that ARF protein is localized to the Golgi apparatus in mammalian cells, in particular to the cytosolic surface of predominantly cis-Golgi membranes. Together, these results indicate that ARF functions in intracellular protein transport to or within the Golgi apparatus, a role not predicted by the previous in vitro biochemical studies.
Many body effects and cluster state quantum computation in strongly interacting systems of photons (2008)

We discuss the basic properties of a recently proposed hybrid light-matter system of strongly interacting photons in an array of coupled cavities each doped with a single two level system. Using the non-linearity generated from the photon blockade effect, we predict strong correlations between the hopping photons in the array, and show the possibility of observing a phase transition from a polaritonic insulator to a superfluid of photons. In the Mott phase, this interaction can be mapped to an array of spins. We show how the remaining Hamiltonian, in conjunction with individual spin manipulation, can thus be used for simulating spin chains (useful for state transfer protocols) and cluster state quantum computation.
Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood–brain barrier dysfunction (2006)

The blood-brain barrier (BBB) formed by brain microvascular endothelial cells (BMVEC) regulates the passage of molecules and leukocytes in and out of the brain. Oxidative stress is a major underlying cause of neurodegenerative and neuroinflammatory disorders and BBB injury associated with them. Using human BMVEC grown on porous membranes covered with basement membrane (BM) matrix (BBB models), we demonstrated that reactive oxygen species (ROS) augmented permeability and monocyte migration across BBB. ROS activated matrix metalloproteinases (MMP-1, -2, and -9) and decreased tissue inhibitors of MMPs (TIMP-1 and -2) in a protein tyrosine kinase (PTK)-dependent manner. Increase in MMPs and PTK activities paralleled degradation of BM protein and enhanced tyrosine phosphorylation of tight junction (TJ) protein. These effects and enhanced permeability/monocyte migration were prevented by inhibitors of MMPs, PTKs, or antioxidant suggesting that oxidative stress caused BBB injury via degradation of BM protein by activated MMPs and by PTK-mediated TJ protein phosphorylation. These findings point to new therapeutic interventions ameliorating BBB dysfunction in neurological disorders such as stroke or neuroinflammation.
Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors (2015)

As a result of our efforts to discover novel p53:MDM2 protein-protein interaction inhibitors useful for treating cancer, the potent and selective MDM2 inhibitor NVP-CGM097 (1) with an excellent in vivo profile was selected as a clinical candidate and is currently in phase 1 clinical development. This article provides an overview of the discovery of this new clinical p53:MDM2 inhibitor. The following aspects are addressed: mechanism of action, scientific rationale, binding mode, medicinal chemistry, pharmacokinetic and pharmacodynamic properties, and in vivo pharmacology/toxicology in preclinical species.
Psychological Factors Associated with Phantom Limb Pain: A Review of Recent Findings (2018)

Phantom limb pain (PLP) is a common phenomenon occurring after the amputation of a limb and can be accompanied by serious suffering. Psychological factors have been shown to play an important role in other types of chronic pain, where they are pivotal in the acquisition and maintenance of pain symptoms. For PLP, however, the interaction between pain and psychological variables is less well documented. In this review, we summarize research on the role of emotional, motivational, cognitive, and perceptual factors in PLP. The reported findings indicate that emotional factors modulate PLP but might be less important compared to other types of chronic pain. Additional factors such as the amount of disability and adjustment to the amputation appear to also play a role. Bidirectional relationships between stress and PLP have been shown quite consistently, and the potential of stress and tension reduction in PLP treatment could be further exploited. Little is known about the role of cognitive variables such as attention or expectation. Catastrophizing seems to aggravate PLP and could be targeted in treatment. Body perception is altered in PLP and poses a potential target for novel mechanistic treatments. More research on psychological factors and their interactions in PLP is needed.