gebhart/patrepeval huggingface dataset:
Corpus-based static branch prediction (1995)

Correctly predicting the direction that branches will take is increasingly important in today's wide-issue computer architectures. The name program-based branch prediction is given to static branch prediction techniques that base their prediction on a program's structure. In this paper, we investigate a new approach to program-based branch prediction that uses a body of existing programs to predict the branch behavior in a new program. We call this approach to program-based branch prediction, evidence-based static prediction, or ESP. The main idea of ESP is that the behavior of a corpus of programs can be used to infer the behavior of new programs. In this paper, we use a neural network to map static features associated with each branch to the probability that the branch will be taken. ESP shows significant advantages over other prediction mechanisms. Specifically, it is a program-based technique, it is effective across a range of programming languages and programming styles, and it does not rely on the use of expert-defined heuristics.
Reconfigurable computing (2002)

Due to its potential to greatly accelerate a wide variety of applications, reconfigurable computing has become a subject of a great deal of research. Its key feature is the ability to perform computations in hardware to increase performance, while retaining much of the flexibility of a software solution. In this survey, we explore the hardware aspects of reconfigurable computing machines, from single chip architectures to multi-chip systems, including internal structures and external coupling. We also focus on the software that targets these machines, such as compilation tools that map high-level algorithms directly to the reconfigurable substrate. Finally, we consider the issues involved in run-time reconfigurable systems, which reuse the configurable hardware during program execution.
Insulin and Insulin-Like Growth Factor I Receptors: Similarities and Differences in Signal Transduction (2001)

The insulin receptor (IR) and the insulin-like growth factor I receptor (IGF-IR) belong to the same subfamily of receptor tyrosine kinases with two extracellular alpha-subunits and two transmembrane beta-subunits. They share a high similarity of structure and intracellular signalling events. However, the IR and the IGF-IR mediate different effects on metabolism, cell proliferation, apoptosis and differentiation. Although some of the variation can be attributed to a different tissue distribution or subcellular localization, it can also be explained by structural differences in the beta-subunit, which may result in activation of specific substrates and signal pathways.
Integrating Target Costing Into Perception-Based Concept Evaluation of Complex and Large-Scale Systems Using Simultaneously Decomposed QFD (2006)

In the conceptual design phase, engineers may need to perceptually screen and prioritize feasible design concepts by their potential to fulfill both customer and financial requirements. This paper presents a system design methodology that integrates perception-based concept evaluation and target costing of complex and large-scale systems. The methodology decomposes a system into modules and evaluates each module concept with its target requirements and cost. This method proposes the decomposition of quality function deployment matrices simultaneously for both requirements and structure in order to allocate the worth and target cost of the modules in a system. Developed from module concepts that satisfy their target requirements and cost, this new system should better satisfy both customer and financial requirements.
Selective esterase–ester pair for targeting small molecules with cellular specificity (2012)

Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase-ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations.
Albumin-bound paclitaxel: a next-generation taxane (2006)

Taxanes are standard treatment for metastatic breast cancer; however, the solvents used as vehicles in these formulations cause severe toxicities. The FDA recently approved a solvent-free formulation of paclitaxel for the treatment of metastatic breast cancer that utilises 130-nanometer albumin-bound (nab) technology (Abraxane; nab-paclitaxel) to circumvent the requirement for solvents. nab-Paclitaxel utilises the natural properties of albumin to reversibly bind paclitaxel, transport it across the endothelial cell and concentrate it in areas of tumour. The proposed mechanism of drug delivery involves, in part, glycoprotein 60-mediated endothelial cell transcytosis of paclitaxel-bound albumin and accumulation in the area of tumour by albumin binding to SPARC (secreted protein, acidic and rich in cysteine). Clinical studies have shown that nab-paclitaxel is significantly more effective than paclitaxel formulated as Cremophor EL (CrEL, Taxol, CrEL-paclitaxel), with almost double the response rate, increased time to disease progression and increased survival in second-line patients. The absence of CrEL from the formulation is associated with decreased neutropenia and rapid improvement of peripheral neuropathy with nab-paclitaxel, compared with CrEL-paclitaxel. For these reasons, nab-paclitaxel can be administered using higher doses of paclitaxel than that achievable with CrEL-paclitaxel, with shorter infusion duration and without the requirement for corticosteroid and antihistamine premedication to reduce the risk of solvent-mediated hypersensitivity reactions. Taken together, these studies have demonstrated that nab technology has increased the therapeutic index of paclitaxel compared with the conventional, solvent-based formulation.
Inhibition of corneal ulceration by tetrapeptidyl hydroxamic acid. (1995)

The inhibitory activity of a new peptidyl collagenase inhibitor, FN-439 or tetrapeptidyl hydroxamic acid (H2N-C6H4-CO-Gly-L-Pro-D-Leu-D-Ala-NHOH), was determined against vertebrate collagenases derived from human fibroblast, human polymorphonuclear leukocyte (PMN) and tadpole skin. In addition, the effect of FN-439 in inhibiting corneal ulceration was also investigated with alkali-burned rabbit corneas. FN-439 can block the active site of collagenase, and hydroxamic acid can chelate Zn2+ which is essential for collagenase activity. Furthermore, this compound contains D-amino acids to resist nonspecific host-derived degradative enzymes. In our experiments, corneal ulceration occurred in 5 of the 9 control eyes, but in none of the 9 eyes treated with FN-439 (P < 0.01). The only cellular elements observed at the ulcerated area were PMNs and monocytes. FN-439 appeared to act against PMN collagenase. In addition, we compared the change in the concentration of FN-439 (D-peptide) and the L-form of FN-439 (L-peptide) in aqueous humor aspirated from the rabbit eyes burned with alkali. After incubation for 3 hours, the concentration of the D-peptide was decreased by 3%, while that of the L-peptide was decreased by 60%. FN-439 may be useful for treating noninfectious corneal ulcers because of its potent activity (IC50 = 1 microM) and chemical and biological stabilities.
RESEARCH REPORT Bexarotene capsules and gel for previously treated patients with cutaneous T‐cell lymphoma: Results of the Australian patients treated on phase II trials (2001)

Bexarotene (Targretin, LGD1069) is a novel synthetic retinoid analogue that binds selectively to retinoid X receptors. We describe eight previously treated patients who entered phase II international multicentre studies examining the role of bexarotene in cutaneous T-cell lymphoma. Patients received either the oral formulation (n = 7) or the topical gel (n = 1). Of the seven patients who received 300 mg/m2 per day capsules, five (71%) achieved a partial response, with mean time to onset of response of 27 days (range, 20-29) with responses persisting for a mean of 92 days (range, 57-115). The single patient receiving the topical preparation (stage IB) remains in partial response at 31 months. The major toxicity with oral administration was hypertriglyceridaemia requiring therapy. Bexarotene capsules and gel are active and generally well-tolerated agents in patients with cutaneous T-cell lymphoma and studies examining its role in previously untreated patients or as part of combination therapy are warranted.
Multi-Microphone Acoustic Echo Cancellation Using Multi-Channel Warped Linear Prediction Of Common Acoustical Poles (2010)

Publication in the conference proceedings of EUSIPCO, Aalborg, Denmark, 2010
Vagal stimulation for the treatment of heart failure: a translational success story (2012)

One of the most inspiring features of medicine is the unending quest for better treatments for the affected patients. This is also the area where experimental and clinical medicine can merge and give rise to translational research. As far as heart failure is concerned, there have been interesting developments. Here, I will review the background that has prompted the initial attempts to modulate autonomic activity, and I will discuss the most recent data and current directions.

Heart failure is characterised by an autonomic imbalance with the combination of sympathetic upregulation and parasympathetic withdrawal, associated with progressive ventricular remodelling, arrhythmia generation and disease progression.1 This type of autonomic imbalance can be quantified at clinical level by baroreflex sensitivity, or by heart rate variability, and is associated with increased mortality after myocardial infarction,2–4 and in heart failure.5 ,6 Acute cardiac decompensation in patients with heart failure is often preceded by signs of further vagal withdrawal.7 Although β-blockers can be used to modify the impact of elevated levels of norepinephrine and the effects of augmented sympathetic tone, the ability of drug therapy to influence parasympathetic function is limited.

These considerations could not be separated by the evidence that increases in vagal activity, either by exercise training8 ,9 or by direct electrical vagal stimulation,10 have a powerful antifibrillatory effect, and can reduce sudden cardiac death. Altogether, they have provided a strong rationale for the evaluation of the potential benefit of chronic vagal stimulation in patients with heart failure.

Potential doubts towards the implementation of a non-traditional treatment were progressively dismissed by the evidence of a clear benefit in different animal models for heart failure,11 and by the fact that chronic vagal stimulation has been used without complications in a very high number of patients with …
Dendritic Cell Sphingosine 1-Phosphate Receptor-3 Regulates Th1–Th2 Polarity in Kidney Ischemia–Reperfusion Injury (2012)

Dendritic cells (DCs) are central to innate and adaptive immunity of early kidney ischemia-reperfusion injury (IRI), and strategies to alter DC function may provide new therapeutic opportunities. Sphingosine 1-phosphate (S1P) modulates immunity through binding to its receptors (S1P1-5), and protection from kidney IRI occurs in S1P3-deficient mice. Through a series of experiments we determined that this protective effect was owing in part to differences between S1P3-sufficient and -deficient DCs. Mice lacking S1P3 on bone marrow cells were protected from IRI, and S1P3-deficient DCs displayed an immature phenotype. Wild-type (WT) but not S1P3-deficient DCs injected into mice depleted of DCs prior to kidney IR reconstituted injury. Adoptive transfer (i.e., i.v. injection) of glycolipid (Ag)-loaded WT but not S1P3-deficient DCs into WT mice exacerbated IRI, suggesting that WT but not S1P3-deficient DCs activated NKT cells. Whereas WT DC transfers activated the Th1/IFN-γ pathway, S1P3-deficient DCs activated the Th2/IL-4 pathway, and an IL-4-blocking Ab reversed protection from IRI, supporting the concept that IL-4 mediates the protective effect of S1P3-deficient DCs. Administration of S1P3-deficient DCs 7 d prior to or 3 h after IRI protected mice from IRI and suggests their potential use in cell-based therapy. We conclude that absence of DC S1P3 prevents DC maturation and promotes a Th2/IL-4 response. These findings highlight the importance of DC S1P3 in modulating NKT cell function and IRI and support development of selective S1P3 antagonists for tolerizing DCs for cell-based therapy or for systemic administration for the prevention and treatment of IRI and autoimmune diseases.
The Carbohydrate at FcγRIIIa Asn-162 (2005)

FcgammaRIIIa plays a prominent role in the elimination of tumor cells by antibody-based cancer therapies. Non-fucosylated bisected IgGs bind this receptor with increased affinity and trigger FcgammaRIII-mediated effector functions more efficiently than native, fucosylated antibodies. In this study the contribution of the carbohydrates of both binding partners to the strength of the complex was analyzed. Glycoengineering of the antibody increased affinity for two polymorphic forms of soluble human FcgammaRIIIa (by up to 50-fold) but did not affect binding to the inhibitory FcgammaRIIb receptor. While the absence of carbohydrate at FcgammaRIIIa's Asn-162 increased affinity for native IgG, presumably due to the removal of steric hindrance caused by the bulky sugars, it unexpectedly reduced affinity for glycoengineered (GE) antibodies by over one order of magnitude, bringing the affinity down to the same level as for native IgG. We conclude that the high affinity between GE antibodies and FcgammaRIII is mediated by productive interactions formed between the receptor carbohydrate attached at Asn-162 and regions of the Fc that are only accessible when it is nonfucosylated. As FcgammaRIIIa and FcgammaRIIIb are the only human Fcgamma receptors glycosylated at this position, the proposed interactions explain the observed selective affinity increase of GE antibodies for only these receptors. Furthermore, we predict from our structural model that only one of the two Fc-fucose residues needs to be absent for increased binding affinity toward FcgammaRIII. This information can be exploited for the design of new antibodies with altered Fc receptor binding affinity and enhanced therapeutic potential.
CL/RAMP2 and CL/RAMP3 produce pharmacologically distinct adrenomedullin receptors: a comparison of effects of adrenomedullin22–52, CGRP8–37 and BIBN4096BS (2003)

Adrenomedullin (AM) has two known receptors formed by the calcitonin receptor-like receptor (CL) and receptor activity-modifying protein (RAMP) 2 or 3: we report the effects of the antagonist fragments of human AM and CGRP (AM22-52 and CGRP8-37) in inhibiting AM at human (h), rat (r) and mixed species CL/RAMP2 and CL/RAMP3 receptors transiently expressed in Cos 7 cells or endogenously expressed as rCL/rRAMP2 complexes by Rat 2 and L6 cells. AM22-52 (10 microM) antagonised AM at all CL/RAMP2 complexes (apparent pA2 values: 7.34+/-0.14 (hCL/hRAMP2), 7.28+/-0.06 (Rat 2), 7.00+/-0.05 (L6), 6.25+/-0.17 (rCL/hRAMP2)). CGRP8-37 (10 microM) resembled AM22-52 except on the rCL/hRAMP2 complex, where it did not antagonise AM (apparent pA2 values: 7.04+/-0.13 (hCL/hRAMP2), 6.72+/-0.06 (Rat2), 7.03+/-0.12 (L6)). On CL/RAMP3 receptors, 10 microM CGRP8-37 was an effective antagonist at all combinations (apparent pA2 values: 6.96+/-0.08 (hCL/hRAMP3), 6.18+/-0.18 (rCL/rRAMP3), 6.48+/-0.20 (rCL/hRAMP3)). However, 10 microM AM22-52 only antagonised AM at the hCL/hRAMP3 receptor (apparent pA2 6.73+/-0.14). BIBN4096BS (10 microM) did not antagonise AM at any of the receptors. Where investigated (all-rat and rat/human combinations), the agonist potency order on the CL/RAMP3 receptor was AM approximately betaCGRP>alphaCGRP. rRAMP3 showed three apparent polymorphisms, none of which altered its coding sequence. This study shows that on CL/RAMP complexes, AM22-52 has significant selectivity for the CL/RAMP2 combination over the CL/RAMP3 combination. On the mixed species receptor, CGRP8-37 showed the opposite selectivity. Thus, depending on the species, it is possible to discriminate pharmacologically between CL/RAMP2 and CL/RAMP3 AM receptors.
Pharmacokinetics of Tenofovir following Intravaginal and Intrarectal Administration of Tenofovir Gel to Rhesus Macaques (2011)

Tenofovir gel (1%) is being developed as a microbicide for the prevention of human immunodeficiency virus (HIV) infection and has been shown to reduce transmission to women by 39%. The gel also prevents infection in macaques when applied intravaginally or intrarectally prior to challenge with simian-human immunodeficiency virus (SHIV), but very little pharmacokinetic information for macaques is available to help extrapolate the data to humans and thus inform future development activities. We have determined the pharmacokinetics of tenofovir in macaques following intravaginal and intrarectal administration of 0.2, 1, and 5% gels. Plasma and vaginal and rectal fluid samples were collected up to 24 h after dosing, and at 24 h postdosing biopsy specimens were taken from the vaginal wall, cervix, and rectum. Following vaginal and rectal administration, tenofovir rapidly distributed to the matrices distal to the site of administration. In all matrices, exposure increased with increasing dose, and with the 1% and 5% formulations, concentrations remained detectable in most animals 24 h after dosing. At all doses, concentrations at the dosing site were typically 1 to 2 log units higher than those in the opposite compartment and 4 to 5 log units higher than those in plasma. Exposure in vaginal fluid after vaginal dosing was 58 to 82% lower than that in rectal fluid after rectal dosing, but plasma exposure was 1- to 2-fold greater after vaginal dosing than after rectal dosing. These data suggest that a tenofovir-based microbicide may have the potential to protect when exposure is via vaginal or anal intercourse, regardless of whether the microbicide is applied vaginally or rectally.
Low-pH induced conformational changes in viral fusion proteins: implications for the fusion mechanism (1995)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Open source development and the World Wide Web (2002)

The development of the World Wide Web over the course of the past ten years has run rampant. The course it has taken has been both swift and unpredictable. The largest distributed system in the world began as a utopian notion of an interconnected and open web of information, the dream of the academic and intellectual alike. Today it is indeed a massive interconnected web of communication and content, but the content, largely on the more popular, if not pornographic, end of the mass media spectrum, is not what the founders intended.Coinciding with the rapid growth of the web has been the equally speedy rise of the open source development community, which can best be understood as a distributed system in its own right. Indeed, the development of the web has been, outside of the Linux project, the largest arena for open source development. And current trends, witnessed by such significant open source projects as Mozilla and Apache, seem to suggest that the open source way of doing things is quickly becoming the web way of doing things. However, there is a certain tension growing between those who would like to control, for economic profit or for the gratification of control itself, the direction of the web's development and those open source developers who are responsible for a large portion of that growth. This paper explores the natural relationship, as well as the growing tension within this relationship, between the open source development community and the World Wide Web.
Precise Control of Polyolefin Stereochemistry Using Single-Site Metal Catalysts (2000)

ADVERTISEMENT RETURN TO ISSUEPREVarticleNEXTPrecise Control of Polyolefin Stereochemistry Using Single-Site Metal CatalystsGeoffrey W. CoatesGeoffrey W. CoatesDepartment of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301 More by Geoffrey W. CoatesCite this: Chem. Rev. 2000, 100, 4, 1223–1252Publication Date (Web):March 25, 2000Publication History Received2 September 1999Published online25 March 2000Published inissue 1 April 2000https://doi.org/10.1021/cr990286uCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views10765Altmetric-Citations1110LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (1 MB) Get e-AlertscloseSUBJECTS:Catalysts,Hydrocarbons,Polymerization,Polymers,Sandwich compounds Get e-Alerts
Multiple drug resistance due to resistance to stem cells and stem cell treatment progress in cancer (Review) (2014)

In recent years, the cancer stem cell (CSC) theory has provided a new angle in the research of cancer, and has gradually gained significance. According to this theory, the multiple drug resistance (MDR) of cancer is most likely due to the resistance of CSCs, and a significant quantity of research has been carried out into the MDR mechanisms of CSC. Over time, some of these mechanisms have been gradually accepted, including ATP-binding cassette transporters, aldehyde dehydrogenase, the CSC microenvironment and epithelial to mesenchymal transition. In the present review, we summarize these mechanisms in detail and review possible appropriate therapy plans against CSCs based on CSC theory.
The Mechanics and Positioning of Highly Flexible Manipulator Limbs (1989)

This paper deals with the analysis of lightweight, flexible robotic limbs. A typical limb is a series of polymeric tube elements. One end is fixed and the payload at the other end is manipulated by varying the internal pressure in each element. The theoretical derivations relating limb position and its payload incorporate the nonlinear elastic properties of the element material and large deflections. A computer program stores information about limb position and after each successive limb manipulation the program adaptively upgrades itself to improve positioning accuracy. Results are illustrated with a numerical example.