gebhart/patrepeval huggingface dataset:
Substitution of Arg527 and Arg531 in factor VIII associated with mild haemophilia A: characterization in terms of subunit interaction and cofactor function (1999)

The functional defect caused by substitution of Arg527 (--> Trp) and Arg531 (--> Gly, His) in factor VIII (FVIII), was explored by employing FVIII derived from patient plasma and recombinant FVIII variants. Mutation of these residues is associated with mild haemophilia A. For both FVIII-R527W and FVIII-R531H, activity was lower than antigen, indicating a functional defect for both variants. In contrast to FVIII-R527W, the amount of FVIII-R531H heterodimer present in plasma was reduced compared to heavy and light chain levels. Factor X (FX) activation experiments employing recombinant FVIII-R531G revealed that the activated FVIII-R531G heterotrimer was less stable than normal FVIIIa, apparently due to rapid dissociation of the A2 domain. These findings suggest that Arg531 is involved in maintaining the stability of both the heterodimer and the activated FVIII heterotrimer. Recombinant FVIII-R527W displayed reduced stimulation of FX activation, suggesting a defect in interaction with factor IXa (FIXa). The contribution of Arg527 in the interaction with FIXa was supported by the observation that FVIII-derived synthetic peptide Tyr511-Leu530 was able to inhibit FX activation and that this inhibition could be overcome by addition of increasing concentrations of FIXa. Furthermore, in the three-dimensional FVIII model residues Val517-Arg527 are located near the FIXa binding site Ser558-Gln565. Therefore we propose that Arg527 is part of an extended FIXa binding site, comprising residues Ser558-Gln565 and Val517-Arg527.
Are certain diuretics also anticonvulsants? (2001)

A history of diuretic use has been shown to be protective for first unprovoked seizure in adult patients. Recent animal studies suggest that certain diuretics have anticonvulsant activity. We evaluated the potential for the anticonvulsant activity of current diuretic use in a population-based, case-control study in older adults. We also tested chlorthiazide and furosemide for seizure protection in animal models of epilepsy. Concurrent medical prescription of any diuretic was protective for the development of epilepsy [odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39-0.99]. A protective effect for current thiazide use was observed (OR = 0.53, CI = 0.31-0.90), and a protective effect for furosemide was suggested (OR = 0.44, CI = 0.1-1.9). In mice, both chlorthiazide and furosemide suppressed the occurrence of maximal electroshock-induced seizures in a dose-dependent manner. Chlorthiazide's toxic dose for 50% of animals tested (TD50) could not be achieved even with dosing as high as 1,500 mg/kg for furosemide; TD50 was 549 mg/kg. Results were similar in rats. Furosemide and chlorthiazide are protective for unprovoked seizures in an epidemiological study and in animal models. Given the potential therapeutic value for seizure control, low toxicity, and low cost, therapeutic efficacy should be explored in clinical studies.
Caspase-Dependent Cdk Activity Is a Requisite Effector of Apoptotic Death Events (2000)

The caspase-dependent activation of cyclin-dependent kinases (Cdks) in varied cell types in response to disparate suicidal stimuli has prompted our examination of the role of Cdks in cell death. We have tested the functional role of Cdk activity in cell death genetically, with the expression of dominant negative Cdk mutants (DN-Cdks) and Cdk inhibitory genes. Here we demonstrate that Cdk2 activity is necessary for death-associated chromatin condensation and other manifestations of apoptotic death, including cell shrinkage and the loss of adhesion to substrate. Susceptibility to the induction of the cell death pathway, including the activation of the caspase cascade, is unimpaired in cells in which Cdk2 activity is inhibited. The direct visualization of active caspase activity in these cells confirms that death-associated Cdk2 acts downstream of the caspase cascade. Cdk inhibition also does not prevent the loss of mitochondrial membrane potential and membrane phospholipid asymmetry, which may be direct consequences of caspase activity, and dissociates these events from apoptotic condensation. Our data suggest that caspase activity is necessary, but not sufficient, for the full physiological cell death program and that a requisite function of the proteolytic caspase cascade is the activation of effector Cdks.
Higher Recovery and Better Energy Dissipation at Faster Strain Rates in Carbon Nanotube Bundles: An in-Situ Study (2012)

We report mechanical behavior and strain rate dependence of recoverability and energy dissipation in vertically aligned carbon nanotube (VACNT) bundles subjected to quasi-static uniaxial compression. We observe three distinct regimes in their stress-strain curves for all explored strain rates from 4 × 10(-2) down to 4 × 10(-4)/sec: (1) a short initial elastic section followed by (2) a sloped plateau with characteristic wavy features corresponding to buckle formation and (3) densification characterized by rapid stress increase. Load-unload cycles reveal a stiffer response and virtually 100% recoverability at faster strain rates of 0.04/sec, while the response is more compliant at slower rates, characterized by permanent localized buckling and significantly reduced recoverability. We propose that it is the kinetics of attractive adhesive interactions between the individual carbon nanotubes within the VACNT matrix that governs morphology evolution and ensuing recoverability. In addition, we report a 6-fold increase in elastic modulus and gradual decrease in recoverability (down to 50%) when VACNT bundles are unloaded from postdensification stage as compared with predensification. Finally, we demonstrate energy dissipation capability, as revealed by hysteresis in load-unload cycles. These findings, together with high thermal and electrical conductivities, position VACNTs in the "unattained-as-of-to-date-space" in the material property landscape.
Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) (2010)

Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.
Heparan sulfate proteoglycans and cancer (2001)

Heparan sulfate proteoglycans (HSPGs) are widely distributed in mammalian tissues and involved in a number of processes related to malignancy. They are composed of a core protein to which chains of the glycosaminoglycan, heparan sulfate (HS), are attached. The existence of various classes of core protein, in addition to highly polymorphic HS chains, creates a superfamily of macromolecules with considerable diversity of structure and function. HSPGs interact with many proteins including growth factors, chemokines and structural proteins of the extracellular matrix to influence cell growth, differentiation, and the cellular response to the environment. The recent identification of two inherited syndromes that are associated with an increased cancer risk, and caused by mutations in HSPG-related genes, has intensified interest in these molecules. This review describes our current understanding of HSPGs in cancer and highlights new possibilities for therapeutic control.
Classifying facial actions (1999)

The Facial Action Coding System (FACS) [23] is an objective method for quantifying facial movement in terms of component actions. This system is widely used in behavioral investigations of emotion, cognitive processes, and social interaction. The coding is presently performed by highly trained human experts. This paper explores and compares techniques for automatically recognizing facial actions in sequences of images. These techniques include analysis of facial motion through estimation of optical flow; holistic spatial analysis, such as principal component analysis, independent component analysis, local feature analysis, and linear discriminant analysis; and methods based on the outputs of local filters, such as Gabor wavelet representations and local principal components. Performance of these systems is compared to naive and expert human subjects. Best performances were obtained using the Gabor wavelet representation and the independent component representation, both of which achieved 96 percent accuracy for classifying 12 facial actions of the upper and lower face. The results provide converging evidence for the importance of using local filters, high spatial frequencies, and statistical independence for classifying facial actions.
Advances in the Use of Dendritic Cells and New Adjuvants for the Development of Therapeutic Vaccines (2003)

The recent advances in immunology and biotechnology have opened new perspectives for the development of immunotherapy strategies against cancer and infectious diseases. The understanding of the pivotal role of dendritic cells in the initiation and regulation of the immune response has led to an ensemble of preclinical studies and pilot clinical trials, which have provided some evidence on the potential advantages of using dendritic cells as cellular adjuvants for the development of therapeutic vaccines against infectious diseases and malignancies. Current research efforts are focused on the definition of optimal protocols for dendritic cell-based therapies in patients. An additional area of emerging importance in the field of immunotherapy is the identification of safe, selective, and more powerful adjuvants, capable not only of enhancing immune protection against pathogens, but also of breaking tolerance against certain tumor-associated antigens, which is the critical issue for the development of cancer vaccines. The recent recognition of the key role of certain cytokines, such as type I interferons, in linking the innate and adaptive immunity through their action on dendritic cells opens new perspectives for using these natural factors as adjuvants for the development of therapeutic vaccines. We review some of the emerging research aspects in immunotherapy, with special attention to the perspectives of using new adjuvants and dendritic cell-based vaccines for the treatment of cancer and infectious diseases.
Characteristics of Human Herpesvirus-6 (1988)

Journal Article Characteristics of Human Herpesvirus-6 Get access C. Lopez, C. Lopez Division of Viral Diseases and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia Please address requests for reprints to Dr. Carlos Lopez, Building 7, Room 206, Centers for Disease Control, Atlanta, Georgia 30333. Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Pellett, P. Pellett Division of Viral Diseases and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Stewart, J. Stewart Division of Viral Diseases and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Goldsmith, C. Goldsmith Division of Viral Diseases and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar K. Sanderlin, K. Sanderlin Division of Viral Diseases and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Black, J. Black Division of Viral Diseases and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Warfield, D. Warfield Division of Viral Diseases and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Feorino P. Feorino Division of Viral Diseases and AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 157, Issue 6, June 1988, Pages 1271–1273, https://doi.org/10.1093/infdis/157.6.1271 Published: 01 June 1988
Automated “Disease/No Disease” Grading of Age-Related Macular Degeneration by an Image Mining Approach (2012)

This study has demonstrated a proof-of-concept, image-mining technique for automated AMD grading. This technique has the potential to be further developed as an automated grading tool for future whole-scale AMD screening programs.
Role of platelet‐derived growth factor in wound healing (1991)

Platelet-derived growth factor (PDGF) is a potent activator for cells of mesenchymal origin. PDGF stimulates chemotaxis, proliferation, and new gene expression in monocytes-macrophages and fibroblasts in vitro, cell types considered essential for tissue repair. Therefore, we analyzed the influence of exogenously administered recombinant B chain homodimers of PDGF (PDGF-BB) on two experimental tissue repair paradigms, incisional and excisional wounds. In both types of wounds, as little as 20-200 picomoles applied a single time to wounds significantly augmented the time dependent influx of inflammatory cells and fibroblasts and accelerated provisional extracellular matrix deposition and subsequent collagen formation. In incisional wounds, PDGF-BB augmented wound breaking strength 50-70% over the first 3 weeks; in excisional wounds, PDGF-BB accelerated time to closure by 30%. PDGF-BB exaggerated, but did not alter, the normal course of soft tissue repair, resulting in a significant acceleration of healing. Long term observations established no apparent differences between PDGF-BB treated and non-treated wounds. Thus, the vulnerary effects of PDGF-BB were transient and fully reversible in both wound healing models. Furthermore, analysis of PDGF-treated and non-treated wounds has provided important insights into mechanisms of normal and deficient tissue repair processes. PDGF appears to transduce its signal through wound macrophages and may trigger the induction of positive autocrine feedback loops and synthesis of endogenous wound PDGF and other growth factors, thereby enhancing the cascade of tissue repair processes required for a fully-healed wound. Thus, PDGF and other wound produced polypeptide growth factors may be the critical regulators of extracellular matrix deposition within healing wounds.
Fetal and infant growth and cardiovascular risk factors in women (1995)

In women, as in men, reduced fetal growth leads to insulin resistance and the associated disorders: raised blood pressure and high serum triglyceride and low serum high density lipoprotein cholesterol concentrations. The highest values of these coronary risk factors occur in people who were small at birth and became obese. In contrast with men, low rates of infant growth did not predict levels of risk factors in women.
Weekly Treatment of 2-Hydroxypropyl-β-cyclodextrin Improves Intracellular Cholesterol Levels in LDL Receptor Knockout Mice (2015)

Recently, the importance of lysosomes in the context of the metabolic syndrome has received increased attention. Increased lysosomal cholesterol storage and cholesterol crystallization inside macrophages have been linked to several metabolic diseases, such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Two-hydroxypropyl-β-cyclodextrin (HP-B-CD) is able to redirect lysosomal cholesterol to the cytoplasm in Niemann-Pick type C1 disease, a lysosomal storage disorder. We hypothesize that HP-B-CD ameliorates liver cholesterol and intracellular cholesterol levels inside Kupffer cells (KCs). Hyperlipidemic low-density lipoprotein receptor knockout (Ldlr(-/-)) mice were given weekly, subcutaneous injections with HP-B-CD or control PBS. In contrast to control injections, hyperlipidemic mice treated with HP-B-CD demonstrated a shift in intracellular cholesterol distribution towards cytoplasmic cholesteryl ester (CE) storage and a decrease in cholesterol crystallization inside KCs. Compared to untreated hyperlipidemic mice, the foamy KC appearance and liver cholesterol remained similar upon HP-B-CD administration, while hepatic campesterol and 7α-hydroxycholesterol levels were back increased. Thus, HP-B-CD could be a useful tool to improve intracellular cholesterol levels in the context of the metabolic syndrome, possibly through modulation of phyto- and oxysterols, and should be tested in the future. Additionally, these data underline the existence of a shared etiology between lysosomal storage diseases and NAFLD.
Targeting gene expression to specific cardiovascular cell types in transgenic mice. (1993)

Transgenic techniques, which allow the introduction of exogenous genes into the genome of experimental animals, promise to bridge the gap between the in vitro observations made by molecular and cellular biologists on cardiac and vascular cells in tissue culture and the physiology and pathology of the whole organ system. One such application of these techniques is tissue targeting: by genetic manipulation to direct expression of a protein--such as a signaling peptide, a growth factor receptor, or an oncogene involved in cell growth--to a tissue where it normally would not be expressed (or where expression is tightly controlled) by fusing it to the transcriptional control sequences of another gene normally expressed in that tissue. In the cardiovascular system, regulatory sequences for cardiomyocyte-specific proteins, vascular endothelium-specific proteins, and smooth muscle-specific proteins can be used to target heterologous genes to their respective tissues in transgenic animals. The effects that such perturbations have on organ physiology and intracellular and intercellular communication can be observed by applying established physiological and molecular approaches. In this review, we highlight some tissue-specific genes from cardiac and vascular cell types whose regulatory sequences may be used to target heterologous proteins; we discuss neutral "reporter" proteins and signal transduction components as paradigms for the application of this technique; and we briefly touch on the potentials and pitfalls of transgenic approaches to molecular physiology.
Simulation of static and dynamic wrinkles of skin (2002)

Wrinkles are an extremely important contribution for enhancing the realism of human figure models. We present an approach to generate static and dynamic wrinkles on human skin. For the static model, we consider micro and macro structures of the skin surface geometry. For the wrinkle dynamics, an approach using a biomechanical skin model is employed. The tile texture patterns in the micro structure of skin surface are created using planar Delaunay triangulation. Functions of barycentric coordinates are applied to simulate the curved ridges. The visible (macro) flexure lines which may form wrinkles are predefined edges on the micro structure. These lines act as constraints for the hierarchical triangulation process. Furthermore, the dynamics of expressive wrinkles-controlling their depth and fold-is modeled according to the principal strain of the deformed skin surface. Bump texture mapping is used for skin rendering.
IPTV session mobility (2008)

This article describes a novel architecture for delivering personalized IPTV experiences to the end users. The framework leverages the IP Multimedia Subsystem (IMS) to quickly enable new innovative, multi-media services. We describe the session flows for a single IPTV session switch between multiple set top boxes (STBs) and between a STB and a PC/mobile device SIP user agent. We also demonstrate how supplementary services like caller ID and advanced telephony features can also be migrated across multiple devices.
PEG and Cholesterol‐Containing Pyromellitates: Synthesis and Self‐Assembly (2013)

A new synthetic route for two different amphiphilic macromolecular structures containing hydrophilic poly(ethylene glycol) (PEG) and lipophilic cholesterol fragments is described. The novelty of the synthesis is in combining hydrophilic and lipophilic fragments in a backbone using functional groups of the pyromellitic dianhydride (PMDA) molecule. The ability of the new oligomers to undergo self‐assembly and solubilization of lipophilic molecules in an aqueous medium is compared. The new oligomers form self‐assemblies capable of solubilizing lipophilic “guest” molecules in an aqueous medium. Their high solubilization capacity and biodegradability, as well as other properties (size distribution, ζ ‐potential), make the synthesized macromolecules good candidates for biomedical applications. Using the developed approach, amphiphilic macromolecules with regulated surface activity can be synthesized by combining PEG of varying lengths with different hydrophobic fragments (for example, fatty alcohols) in the backbone. image
$\text{D}^{\textit{over}}$: An Optimal On-Line Scheduling Algorithm for Overloaded Uniprocessor Real-Time Systems (1995)

Consider a real-time system in which every task has a value that it obtains only if it completes by its deadline. The problem is to design an on-line scheduling algorithm (i.e., the scheduler has no knowledge of a task until it is released) that maximizes the guaranteed value obtained by the system. When such a system is underloaded (i.e., there exists a schedule for which all tasks meet their deadlines), Dertouzos [Proceedings IFIF Congress, 1974, pp. 807–8131 showed that the earliest deadline first algorithm will achieve 100% of the possible value. Locke [Ph.D. thesis, Computer Science Dept., Carnegie-Mellon Univ., Pittsburgh, PA] showed that earliest deadline first performs very badly, however, when the system is overloaded, and he proposed heuristics to deal with overload. This paper presents an optimal on-line scheduling algorithm for overloaded uniprocessor systems. It is optimal in the sense that it gives the best competitive ratio possible relative to an off-line scheduler.