gebhart/patrepeval huggingface dataset:
Quantification and toxicity of group A streptococcal pyrogenic exotoxins in an animal model of toxic shock syndrome-like illness (1989)

Toxic shock-like syndrome isolates of group A streptococci were evaluated for production of pyrogenic exotoxins (also called SPEs, scarlet fever toxins, and erythrogenic toxins). The isolates were consecutively obtained during 1987 and 1988. Of these isolates, 23 of 26 made SPE type A, 10 of 26 made SPE B, and 8 of 26 made SPE C. SPE A was produced in significantly greater amounts than SPEs B and C (3.2 micrograms/ml of culture fluid compared with 0.7 and 0.6 microgram/ml, respectively). SPE A, administered in miniosmotic pumps implanted subcutaneously in rabbits, was significantly more toxic than SPE C; seven of eight rabbits succumbed after challenge with 150 or 300 micrograms of SPE A, compared with one of six after challenge with SPE C.
Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients (2014)

Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.
The Role of the Central Nucleus of the Amygdala in Mediating Fear and Anxiety in the Primate (2004)

Numerous studies demonstrate that the rhesus monkey is an excellent species with which to investigate mechanisms underlying human emotion and psychopathology. To examine the role of the central nucleus of the amygdala (CeA) in mediating the behavioral and physiological responses associated with fear and anxiety, we used rhesus monkeys to assess the effects of excitotoxic lesions of the CeA. Behavioral and physiological responses of nine monkeys with bilateral CeA destruction (ranging from 46 to 98%) were compared with five animals with asymmetric lesions (42-86.5% destruction on the most affected side) and with 16 unoperated controls. Results suggest that similar to rodent species, the primate CeA plays a role in mediating fear- and anxiety-related behavioral and endocrine responses. Compared with controls and the asymmetric-lesion group, bilaterally lesioned monkeys displayed significantly less fear-related behavior when exposed to a snake and less freezing behavior when confronted by a human intruder. In addition, bilaterally lesioned monkeys had decreased levels of CSF corticotrophin-releasing factor (CRF), and both lesioned groups had decreased plasma ACTH concentrations. In contrast to these findings, patterns of asymmetric frontal brain electrical activity, as assessed by regional scalp EEG, did not significantly differ between control and lesioned monkeys. These findings suggest that in primates, the CeA is involved in mediating fear- and anxiety-related behavioral and pituitary-adrenal responses as well as in modulating brain CRF activity.
Molecular Mechanism of Hepatitis C Virus Replicon Variants with Reduced Susceptibility to a Benzofuran Inhibitor, HCV-796 (2008)

HCV-796 selectively inhibits hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. In hepatoma cells containing a genotype 1b HCV replicon, HCV-796 reduced HCV RNA levels by 3 to 4 log(10) HCV copies/mug total RNA (the concentration of the compound that inhibited 50% of the HCV RNA level was 9 nM). Cells bearing replicon variants with reduced susceptibility to HCV-796 were generated in the presence of HCV-796, followed by G418 selection. Sequence analysis of the NS5B gene derived from the replicon variants revealed several amino acid changes within 5 A of the drug-binding pocket. Specifically, mutations were observed at Leu314, Cys316, Ile363, Ser365, and Met414 of NS5B, which directly interact with HCV-796. The impacts of the amino acid substitutions on viral fitness and drug susceptibility were examined in recombinant replicons and NS5B enzymes with the single-amino-acid mutations. The replicon variants were 10- to 1,000-fold less efficient in forming colonies in cells than the wild-type replicon; the S365L variant failed to establish a stable cell line. Other variants (L314F, I363V, and M414V) had four- to ninefold-lower steady-state HCV RNA levels. Reduced binding affinity with HCV-796 was demonstrated in an enzyme harboring the C316Y mutation. The effects of these resistance mutations were structurally rationalized using X-ray crystallography data. While different levels of resistance to HCV-796 were observed in the replicon and enzyme variants, these variants retained their susceptibilities to pegylated interferon, ribavirin, and other HCV-specific inhibitors. The combined virological, biochemical, biophysical, and structural approaches revealed the mechanism of resistance in the variants selected by the potent polymerase inhibitor HCV-796.
Rosiglitazone prevents nutritional fibrosis and steatohepatitis in mice (2008)

The present study provides clear morphological and molecular biological evidence of the protective role of rosiglitazone in ameliorating nutritional fibrosing steatohepatitis. Rosiglitazone may ameliorate hepatic fibrosis by activating PPAR gamma, which can inhibit HSC activation and suppress TGF-beta1 and CTGF expression.
Mastering Bitcoin: Unlocking Digital Crypto-Currencies (2014)

Mastering Bitcoin is essential reading for everyone interested in learning about bitcoin basics, the technical operation of bitcoin, or if you're building the next great bitcoin killer app or business. From using a bitcoin wallet to buy a cup of coffee, to running a bitcoin marketplace with hundreds of thousands of transactions, or collaboratively building new financial innovations that will transform our understanding of currency and credit, this book will help you engineer money. You're about to unlock the API to a new economy. This book is your key. This book will help you learn everything you need to know about decentralized digital money, which is one of the most exciting technical revolutions in decades. Just as the Internet has transformed dozens of industries - from media and entertainment to retailing, travel and many more - decentralized digital money, in the form of crypto-currencies, has the ability to transform the foundations of money, credit and financial services. It also has the power to transform other social activities and institutions that we don't usually associate directly with money, such as corporations, governance, voting and the law. As the first successful digital currency, bitcoin is the natural starting point for anyone interested in decentralized digital money, its implications and applications. Mastering Bitcoin describes the technical foundations of bitcoin and other cryptographic currencies, from cryptography basics, such as keys and addresses, to the data structures, network protocols and the consensus mechanism (mining) that underpin bitcoin. Each technical topic is explained with user stories, elegant analogies and examples, and code snippets illustrating the key concepts. The first two chapters offer a broad and accessible introduction to bitcoin that is intended for all audiences, from new non-technical users to investors and business executives seeking to better understand bitcoin. The remainder of the book dives into the technical details of bitcoin's operation and is aimed at professional developers, engineers, software and systems architects, systems administrators and technically-minded people interested in the inner workings of bitcoin and comparable crypto-currencies. Mastering Bitcoin is intended to be used as a reference book for technical professionals, as a self-study guide for bitcoin entrepreneurs, and as a textbook for university courses on bitcoin and digital currencies. Bitcoin is still in its infancy, and yet it has already spawned a multi-billion dollar, global economy that is growing exponentially. Both new and established companies are adding bitcoin as a payment method, and investors are funding a flurry of new bitcoin and related startups. Mastering Bitcoin can help you become part of this vibrant new economy. The time to get started is now.
Building secure healthcare services using OAuth 2.0 and JSON web token in IOT cloud scenario (2016)

OAuth 2.0 is a delegated authorization framework enabling secure authorization for applications running on various kinds of platforms. In healthcare services, OAuth allows the patient (resource owner) seeking real time clinical care to authorize automatic monthly payments from his bank account (resource server) without the patient being required to supply his credentials to the clinic (client app). OAuth 2.0 achieves this with the help of tokens issued by an authorization server which enables validated access to a protected resource. To ensure security, access tokens have an expiry time and are short-lived. So the clinical app may use a refresh token to obtain a new access token to cash monthly payments for rendering real time health care services. Refresh tokens need secure storage to ensure they are not leaked, since any malicious party can use them to obtain new access and refresh tokens. Since OAuth 2.0 has dropped signatures and relies completely on SSL/TLS, it is vulnerable to phishing attack when accessing interoperable APIs. In this paper, we develop an approach that combines JSON web token (JWT) with OAuth 2.0 to request an OAuth access token from authorization server when a client wishes to utilize a previous authentication and authorization. Experimental evaluation confirms that the proposed scheme is practically efficient, removes secure storage overhead by removing the need to have or store refresh token, uses signature and prevents different security attacks which is highly desired in health care services using an IOT cloud platform.
Human Papillomavirus Types 16 and 18 in Adenocarcinoma of the Uterine Cervix (1991)

Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival.
NTP Concentration Switches Transcriptional Activity by Changing the Large-Scale Structure of DNA (2003)

It is becoming clearer that genetic activity is closely associated with the intracellular energy state. However, the mechanisms of this association are still unclear. In this study, we focused on large-scale changes in the structure of DNA to examine the effect of the NTP concentration on the transcription reaction with T7 RNA polymerase and compared the results with long duplex DNA to those with a short persistent-length(1) fragment. The transcriptional activity dramatically changed only for long duplex DNA within a narrow range of NTP concentrations associated with changes in the large-scale structure of DNA. This result suggests that the energy state may play an essential role in regulating ON/OFF switching on transcriptional activity.
Tumour necrosis factor-α antagonists and their therapeutic applications (1998)

Tumour necrosis factor-α (TNF-α) is a cytokine essential for regulation of normal cellular processes while its overproduction can be implicated in the pathology of many inflammatory disorders. Consequently, stemming the deleterious actions of TNF-α via any of several routes is an attractive and highly competitive area of research. Small molecule inhibitors have been developed either to inhibit the production of TNF-α by cAMP potentiation and blocking TNF-α gene expression (phosphodiesterase 4 inhibitors) or to inhibit TNF-α processing (matrix metalloproteinase inhibitors). The development of monoclonal antibody technology is a rapidly expanding field. This has improved to such an extent that many clinical trials are underway and have shown promising results.
Assembly and transcription of synthetic vesicular stomatitis virus nucleocapsids (1991)

The functional template for transcription of vesicular stomatitis virus (VSV) RNA is a ribonucleoprotein particle (nucleocapsid) consisting of the negative-strand sense genomic RNA completely encapsidated by the viral nucleocapsid (N) protein. As an approach to create nucleocapsids in vitro, we demonstrate here the specific encapsidation by purified N protein of in vitro-synthesized RNA sequences representing the 5' end of both the negative- and positive-strand VSV genome-length RNAs. As few as 19 nucleotides from the 5'-end of positive-strand RNA allowed maximal encapsidation, although the 5' terminal 10 nucleotides would allow partial (50%) encapsidation. Sequences downstream of the binding site can be of any origin. Specific encapsidation of VSV sequences was dependent on the presence of uninfected cell cytoplasmic extracts or poly(A). The synthetic nucleocapsids have the properties of RNase resistance and a buoyant density typical of wild-type VSV nucleocapsids. We have encapsidated a synthetic virionlike RNA species which contained just the terminal sequences of the virion RNA: the N encapsidation signal from the 5' end and the leader gene from the 3' end. This assembled nucleocapsid could function in vitro as a transcription template for the VSV RNA polymerase.
Methotrexate in the Treatment of Corticosteroid-Dependent Asthma (1988)

To test our previous observation that methotrexate reduces corticosteroid requirements of patients with severe asthma, we studied 14 patients with corticosteroid-dependent bronchial asthma in a 24-week randomized double-blind crossover trial comparing a low dosage of methotrexate (15 mg per week) with placebo. At base line the mean dosage of prednisone was 173.5 mg per week (range, 70 to 420). On the average, 36.5 percent less prednisone was required when patients received methotrexate than when they received placebo (P = 0.01). Measurement of forced vital capacity and forced expiratory volume in one second showed that there was no deterioration in the condition of patients in whom the dosage of prednisone was reduced. The patients' subjective assessment of breathing ability indicated significant improvement (P = 0.01). The adverse effects of methotrexate were limited to transient nausea in three patients and an evanescent rash in one patient. Nine patients are still receiving methotrexate 3 to 10 months after the study's conclusion. The dosages of steroids have been further reduced in each of these patients, and prednisone has been discontinued in four. We conclude from this preliminary study that the use of methotrexate allows a significant reduction in the use of corticosteroids in patients with severe asthma without deterioration of pulmonary function.
On periodic resource scheduling for continuous media databases (2002)

The Enhanced Pay-Per-View (EPPV) service model provides an effective way of delivering continuous media (CM) data clips to a large number of different clients. The aim is to share CM streams among various clients, thereby increasing the level of concurrency beyond the capacity limitations of available resources, while guaranteeing an upper bound on the clients' waiting time. In the EPPV service model, waiting time guarantees are provided by means of a regular playback schedule, where each continuous media clip is displayed periodically with a frequency that depends on factors such as the clip's popularity. Efficiency is achieved by sharing these periodic CM streams among multiple clients. The EPPV model offers a number of advantages over other schemes, which makes it more attractive to large-scale service providers. This paper provides an overview of our recent results on the resource scheduling problems associated with supporting EPPV for continuous media clips with (possibly) different display rates, frequencies, and lengths; and outlines a number of open research problems related to the EPPV service model. A major contribution of our work is the introduction of a robust scheduling framework that, we believe, can provide solutions for a variety of realistic EPPV resource scheduling scenarios, as well as any scheduling problem involving regular, periodic use of a shared resource. Based on this framework, we propose various interesting research directions for extending the results presented.
Scheduling and partitioning ANSI-C programs onto multi-FPGA CCM architectures (1996)

The increasing size and speed of modern FPGAs allow complex computations, on the order of an average sized program, to be performed in a small collection of processing elements. It is well documented that the execution of large sections of a program within the "virtual hardware" offered by an attached FPGA processor can provide substantial speedup over the ordinary execution within a sequential, general-purpose processor. Unfortunately, the development tools currently available for FPGAs do not allow for easily configuring multi-FPGA custom computing machines. Configuration of an FPGA architecture requires scheduling: the mapping of computations onto existing functional units. To take advantage of all available logic, computations may span processing elements, calling for partitioning of a subroutine between one or more FPGAs. In this paper, an architecture-independent design tool is presented for translating programs written in C to a dataflow representation and then efficiently scheduling and partitioning the resulting graphs onto multi-FPGA computing platforms.
The NAPA adaptive processing architecture (2002)

The National Adaptive Processing Architecture (NAPA) is a major effort to integrate the resources needed to develop teraops class computing systems based on the principles of adaptive computing. The primary goals for this effort include: (1) the development of an example NAPA component which achieves an order of magnitude cost/performance improvement compared to traditional FPGA based systems, (2) the creation of a rich but effective application development environment for NAPA systems based on the ideas of compile time functional partitioning and (3) significantly improve the base infrastructure for effective research in reconfigurable computing. This paper emphasizes the technical aspects of the architecture to achieve the first goal while illustrating key architectural concepts motivated by the second and third goals.
Cardiac-Selective Expression of Extracellular Superoxide Dismutase After Systemic Injection of Adeno-Associated Virus 9 Protects the Heart Against Post–Myocardial Infarction Left Ventricular Remodeling (2013)

Cardiac-selective expression of EcSOD from the cardiac troponin-T promoter after systemic administration of AAV9 provides significant protection against both acute MI and LV remodeling.
Analysis of Mammalian ras Effector Function (1988)

Over the last 8 years or so, a great deal of effort has been put into understanding the biochemical function of the three mammalian p21ras proteins. Single-aminoacid alterations in these three proteins have been detected in 25–50% of some types of human cancers, and it is believed that the somatic mutational event that generated these amino acid substitutions is an important step in the development of these malignancies (Barbacid 1986; Bos et al. 1987; Paterson et al. 1987). Understanding the normal role of p21ras and the effects of oncogenic mutations is therefore clearly of immense importance.
Dimensionally Modulated, Single-Crystalline LiMPO4 (M= Mn, Fe, Co, and Ni) with Nano-Thumblike Shapes for High-Power Energy Storage (2009)

We demonstrate an efficient and rapid microwave irradiated solvothermal method to prepare nanostructured lithium metal phosphates LiMPO(4) (M = Mn, Fe, Co, and Ni) within a short reaction time (5-15 min) at temperatures as low as 300 degrees C without requiring any post annealing at elevated temperatures. The highly viscous, high-boiling tetraethyleneglycol used as the solvent not only provides a reducing atmosphere to prevent the oxidation of M(2+) to M(3+) but also inhibits the agglomeration of the nanoparticles formed. The enhanced reaction rates facilitated by the dielectric volumetric heating of the microwave absorbing reactants led to the formation of highly crystalline, phase-pure LiMPO(4) powders. The samples are characterized by X-ray diffraction, Raman spectroscopy, transmission electron microscopy (TEM), and electrochemical measurements in lithium cells. High-resolution TEM studies reveal the formation of single-crystalline LiMPO(4) with nano-thumblike shapes. The dimensionally modulated nano-thumblike shapes with the lithium diffusion direction (b axis) along the shorter dimension are particularly beneficial to achieve high-power capability in lithium ion cells. Subsequent networking of the single-crystalline LiMPO(4) nano-thumps with multiwalled carbon nanotubes by a simple solution-based mixing at ambient temperatures to overcome the electronic conductivity limitations offers excellent electrochemical performance in lithium ion cells.
Transfection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells. (1996)

Aggregation of the high affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells results in rapid tyrosine phosphorylation and activation of Syk, a cytoplasmic protein tyrosine kinase. To examine the role of Syk in the Fc epsilon RI signaling pathway, we identified a variant of RBL-2H3 cells that has no detectable Syk by immunoblotting and by in vitro kinase reactions. In these Syk-deficient TB1A2 cells, aggregation of Fc epsilon RI induced no histamine release and no detectable increase in total cellular protein tyrosine phosphorylation. However, stimulation of these cells with the calcium ionophore did induce degranulation. Fc epsilon RI aggregation induced tyrosine phosphorylation of the beta and gamma subunits of the receptor, but no increase in the tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2 and no detectable increase in intracellular free Ca2+ concentration. By transfection, cloned lines were established with stable expression of Syk. In these reconstituted cells, Fc epsilon RI aggregation induced tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2, an increase in intracellular free Ca2+ and histamine release. These results demonstrate that Syk plays a critical role in the early Fc epsilon RI-mediated signaling events. It further demonstrates that Syk activation occurs downstream of receptor phosphorylation, but upstream of most of the Fc epsilon RI-mediated protein tyrosine phosphorylations.