gebhart/patrepeval huggingface dataset:
Design of JFluid: a profiling technology and tool based on dynamic bytecode instrumentation (2003)

Instrumentation-based profiling has many advantages and one serious disadvantage: usually high performance overhead. This overhead can be substantially reduced if only a small part of the target application (for example, one that has previously been identified as a performance bottleneck) is instrumented, while the rest of the application code runs at full speed. Such an approach can also beat scalability issues caused by a high volume of profiling information generated by instrumented code running on behalf of multiple threads. The value of such a profiling technology would increase further if the code could be instrumented and de-instrumented as many times as needed at run time.

In this report we describe in detail the design of an experimental profiling system called JFluid, which includes a modified Java HotSpot™ VM and a GUI tool, and addresses both of the above issues. Our JVM™ supports arbitrary on-the-fly modifications to running Java methods, and can connect with a profiling tool at any moment, without any startup time preparation. Our tool collects, processes and presents profiling data on-line. To perform CPU profiling, it instruments a group of methods defined as an arbitrary root method plus all methods that it calls (a call subgraph). It appears that static determination of all methods in a call subgraph is difficult in the presence of virtual methods, but fortunately, with dynamic code hotswapping available, two schemes of dynamic call subgraph revelation and instrumentation can be suggested.

Measurements that we obtained when performing full and partial program profiling using both schemes show that the overhead can be reduced substantially using this technique, and that one of the schemes generally results in a smaller number of instrumented methods and better performance, especially for large applications.
Dendrimer Nanoparticles for Ocular Drug Delivery (2013)

Eye is a unique organ of perfection and complexity, and is a microcosm of the body in many ways. It represents a great opportunity for nanomedicine, since it is readily accessible-allowing for direct drug/gene delivery to maximize the therapeutic effect and minimize side effects. The development of appropriate delivery systems that can sustain and deliver therapeutics to the target tissues is a key challenge that can be addressed by nanotechnology. Dendrimers are tree-like, nanostructured polymers that have received significant attention as ocular drug delivery systems, due to their well-defined size, tailorable structure, and potentially favorable ocular biodistribution. In this review, we highlight recent developments in dendrimer-based ocular therapies for both anterior and posterior segment diseases.
Peptide and Protein Library Screening Defines Optimal Substrate Motifs for AKT/PKB (2000)

AKT was originally identified as a proto-oncogene with a pleckstrin homology and Ser/Thr protein kinase domains. Recent studies revealed that AKT regulates a variety of cellular functions including cell survival, cell growth, cell differentiation, cell cycle progression, transcription, translation, and cellular metabolism. To clarify the substrate specificity of AKT, we have used an oriented peptide library approach to determine optimal amino acids at positions N-terminal and C-terminal to the site of phosphorylation. The predicted optimal peptide substrate (Arg-Lys-Arg-Xaa-Arg-Thr-Tyr-Ser*-Phe-Gly where Ser* is the phosphorylation site) has similarities to but is distinct from optimal substrates that we previously defined for related basophilic protein kinases such as protein kinase A, Ser/Arg-rich kinases, and protein kinase C family members. The positions most important for high V(max)/K(m) ratio were Arg-3>Arg-5>Arg-7. The substrate specificity of AKT was further investigated by screening a lambdaGEX phage HeLa cell cDNA expression library. All of the substrates identified by this procedure contained Arg-Xaa-Arg-Xaa-Xaa-(Ser/Thr) motifs and were in close agreement with the motif identified by peptide library screening. The results of this study should help in prediction of likely AKT substrates from primary sequences.
Vascular Endothelial Growth Factor - Its Relation to Neovascular ization and Their Significance as Prognostic Factors in Renal Cell Carcinoma (2001)

Angiogenesis is a series of processes that include endothelial proliferation, migration and tube formation. Vascular endothelial growth factor (VEGF) is regarded as a potent mediator of angiogenesis, vascular permeability and tumor cell growth in renal cell carcinoma. This study was designed to evaluate the expression of VEGF and the microvessel count (MVC) and to determine their prediction efficacies for prognosis in renal cell carcinoma. The relationship between the expression of VEGF and MVC were evaluated immunohistochemically in 50 patients with renal cell carcinoma who received a radical nephrectomy at Wonju Christian Hospital between 1989 and 1997. Microvessels were identified by immunostaining endothelial cells for CD-31 antigen. The mean follow-up was 96 months (3 - 133 months). Overall 5-year survival rate was 71.5%. VEGF was expressed in the tumor cell cytoplasm. Of the 50 tumors, 23 (46%) were weak to strongly positive for VEGF but 27 (54%) were unreactive. The respective 5-year survival rates for patients with positive and negative expressions of VEGF were 70% and 73% (p > 0.05). The overall mean MVC was 13.4 in a 400x field. Mean MVCs were significantly higher in VEGF-positive tumors (17.6 +/- 12.1) than in VEGF-negative tumors (9.9 +/- 5.4), and the MVCs of the high vascular density group and the low vascular density groups were significantly different. The 5-year survival rates of patients with high vascular density and low vascular density were 59% and 86%. The median survival period for patients with MVCs higher than or equal to 10 vessels/field was 85 months, whereas for those with MVCs lower than 10 vessels/field the median survival time was 102 months. These results suggest that MVC may be a better prognostic factor in renal cell carcinoma than the expression of VEGF.
Sphingosine Kinase 1 Regulates Differentiation of Human and Mouse Lung Fibroblasts Mediated by TGF-β1 (2007)

Transforming growth factor beta (TGF-beta) contributes to the progression of pulmonary fibrosis through up-regulation of alpha-smooth muscle actin (alpha-SMA) as lung myofibroblast differentiation. Bioactive sphingosine 1-phosphate (S1P) has been shown to mimic TGF-beta signals; however, the function of S1P in lung fibrotic process has not been well documented. We found, in a mouse model of bleomycin lung fibrosis, that SPHK1 and alpha-SMA were colocalized within lung fibrotic foci and that these expressions were significantly increased in primary cultured fibroblasts. Using human lung fibroblasts WI-38, we explored the rationale of sphingosine kinase (SPHK) with TGF-beta1 stimulation. SPHK inhibitors and small interference RNA (siRNA) targeted SPHK1 decreased alpha-SMA and fibronectin expression up-regulated by TGF-beta1. In the meantime, SPHK1 inhibition did not affect smad2 phosphorylation in response to TGF-beta1. Then we examined whether S1P receptors transactivation may affect TGF-beta signals. siRNA against S1P(2) and S1P(3), but not S1P(1), reduced alpha-SMA expression as well as Y-27632, Rho kinase inhibitor. We also detected activation of Rho GTPase upon stimulation of TGF-beta1 on the cell membrane where S1P(2) or S1P(3) was overexpressed. These data suggested that SPHK1 activation by TGF-beta1 leads to Rho-associated myofibroblasts differentiation mediated by transactivated S1P receptors in the lung fibrogenic process.
VP22 light controlled delivery of oligonucleotides to ocular cells in vitro and in vivo. (2005)

In vitro, VP22 light controlled delivery of ODNs to ocular cells nuclei was feasible using white light or laser illumination. In vivo, a single intravitreal injection of vectosomes, followed by transscleral illumination allowed for the delivery of free ODNs to retinal and RPE cells.
DOLOP—database of bacterial lipoproteins (2002)

The website called Database Of bacterial LipOProteins (DOLOP) is available at http://www.mrc-lmb.cam.ac.uk/genomes/dolop along with additional information on the biosynthetic pathway, supplementary material and other related figures.
Design of an endoluminal NOTES robotic system (2007)

Natural orifice transluminal endoscopic surgery, or NOTES, allows for exceedingly minimally invasive surgery but has high requirements for the dexterity and force capabilities of the tools. An overview of the ViaCath System is presented. This system is a first generation teleoperated robot for endoluminal surgery and consists of a master console with haptic interfaces, slave drive mechanisms, and 6 degree-of-freedom, long-shafted flexible instruments that run alongside a standard gastroscope or colonoscope. The system was validated through animal studies. It was discovered that the devices were difficult to introduce into the GI tract and manipulation forces were insufficient. The design of a second generation system is outlined with improvements to the instrument articulation section and a steerable overtube. Results of basic evaluation tests performed on the tools are also presented.
Enhancement of liposomal gene delivery in human breast cancer cells by dimethyl sulfoxide. (1998)

Non-toxic concentrations ( 1%) of dimethyl sulfoxide (DMSO) enhance the liposomal delivery of DNA to both MCF-7 and MDA-MB-231 human breast tumor cells. Uptake of SV-40-luciferase was enhanced in MCF-7 cells by 14-fold while uptake of CMV-beta-galactosidase was increased 10-fold. In MDA-MB-231 cells, uptake of SV-40-luciferase was increased by approximately 70%. A mixture of ethanol and polyethylene glycol (45:55) at a concentration of 1% produced less pronounced improvements in transgene delivery to MCF-7 cells (a 70% increase in SV-40-luciferase uptake and a 4-fold increase in CMV-beta-galactosidase uptake) but no improvement in SV-40-luciferase gene delivery to MDA-MB-231 cells. These studies suggest that select pharmaceutical adjuvants which dissolve clinically useful drugs may have promise as non-toxic vehicles for improving transgene delivery. However, the relative effectiveness of these adjuvants is likely to vary depending on both the nature of the gene being delivered as well as the tumor cell which is the target for uptake of the exogenous gene.
Measurement‐based evaluation of optical pathlength distributions reconstructed from simulated differential interference contrast images (1998)

Recently a method was presented for reconstructing optical pathlength distributions (OPDs) from images of weak phase objects obtained by a conventional differential interference contrast (DIC) microscope. A potential application of this technique is the determination of the mass of biological objects: by integrating the optical pathlength over the projected surface of the image of an object, a measure of the dry mass, i.e. the total mass of all solid constituents present in the object, is obtained. To assess the possibilities of DIC microscopy for this application, simulations were performed on computer-generated DIC images of objects of various sizes, shapes and orientation angles. After reconstructing the OPDs from these images, the integrated optical pathlength of each of the test objects was determined, and compared with the expected results. The parameter settings used in the reconstruction algorithm were found to be very important in obtaining a reliable measurement. Using optimal parameter settings, errors in the integrated OPD could be limited to a few per cent for circular objects within the investigated size range. For non-circular objects, however, the orientation angle of the object relative to the lateral shift was found to influence the measured values. Ellipses with their long axes perpendicular to the shift direction had a significantly higher integrated OPD than ellipses orientated parallel to the shift. By adjusting the reconstruction parameters the effect could be limited, but complete elimination of the artefact was not possible within the parameter range investigated.
Histoplasmosis in Normal Hosts (1981)

From the Pulmonary Disease Section and the Medical Service, Veterans Administration Medical Center, and the Department of Medicine, Vanderbilt University, Nashville, Tennessee. 2Pulmonary Fellow
Control Synthesis of Silver Nanosheets, Chainlike Sheets, and Microwires via a Simple Solvent−Thermal Method (2007)

In this work, we present a facile method to synthesize silver nanosheets, chainlike sheets, and microwires via decomposition of the AgNO3 in ethanol in the presence of ammonia. The obtained samples have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), selected-area electronic diffraction (SAED), and energy dispersive X-ray analysis (EDXA). The experiments show that the concentration of ammonia, reaction temperature, and time are important factors for controlling the morphology of the products. On the basis of our experimental results, we propose an ammonia-tuning Oswald ripening mechanism to elucidate the formation of different morphologies of silver structures such as the nanosheets, chainlike sheets, and microwires. The current−voltage characteristic of the individual silver microwire shows linear behavior, and the electrical conductivity of the silver microwire is found to be comparable to that of the bulk silver materials, indicating that it can serve as interconnect in fabricating the micro/nanodevices.
X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-beta conformation. (1986)

Information about the structure of the paired helical filaments (PHF) that accumulate within human neurons and the amyloid fibers that accumulate in the extracellular spaces between neurons in Alzheimer disease has so far depended on electron microscopy of thin-sectioned or negatively stained material. To determine the protein conformation of these abnormal fibers, we have obtained x-ray diffraction patterns from unfixed human brain fractions highly enriched in PHF and from purified amyloid cores isolated from senile plaques. The predominant x-ray scatter evident from both types of samples, either wet or dry, is a sharp reflection at 4.76-A spacing and a diffuse one at about 10.6-A spacing. These features are characteristic of a beta-pleated sheet type of protein conformation. In doubly oriented dried pellets of PHF fractions, the two reflections are accentuated at right angles to each other and the arc at 4.76-A spacing is in the fiber direction indicating a cross-beta conformation. From the integral widths of the reflections we estimate the cross-beta crystallite to be about 80 A long in the fiber direction and about 40 A thick. These dimensions correspond to approximately four pleated sheets, each of which consists of approximately 16 hydrogen-bonded polypeptide chains running normal to the fiber direction. The cross-beta conformation of PHF and amyloid fibers that we have found from x-ray diffraction is in contrast to the predominant alpha-helical coiled-coil conformation of the neurofilaments with which they share epitopes and from which they have been postulated to derive.
Characterization of Nicotinic Receptor‐Mediated [3H]Dopamine Release from Synaptosomes Prepared from Mouse Striatum (1992)

This study establishes that presynaptic nicotinic receptors modulate dopamine release in the mouse striatum. Nicotinic agonists elicit a dose-dependent increase in the release of [3H]dopamine from synaptosomes prepared from mouse striatum. At low concentrations, this release is Ca2+ dependent, whereas at higher concentrations Ca(2+)-independent, mecamylamine-insensitive release was also observed. The Ca(2+)-dependent nicotine-evoked release was not blocked by alpha-bungarotoxin but was effectively blocked by neuronal bungarotoxin as well as several other nicotinic receptor antagonists. The relationship between potency for stimulation of release for agonists and potency for inhibition of release for antagonists was compared to the affinity of these compounds for the [3H]nicotine binding site. The overall correlation between release and binding potency was not high, but the drugs may be classified into separate groups, each of which has a high correlation with binding. This finding suggests either that more than one nicotinic receptor regulates dopamine release or that not all agonists interact with the same receptor in an identical fashion.
The unusual tetrasaccharide sequence GlcAβ-3GalNAc(4-sulfate)(β1–4GlcA(2-sulfate)β1–3GalNAc(6-sulfate) found in the hexasaccharides prepared by testicular hyaluronidase digestion of shark cartilage chondroitin sulfate D (1997)

Eight hexasaccharide fractions were isolated from commercial shark cartilage chondroitin sulfate D by means of gel filtration chromatography and HPLC on an aminebound silica column after exhaustive digestion with sheep testicular hyaluronidase. Capillary electrophoresis of the enzymatic digests as well as one- and two-dimensional 500 MHz 1H-NMR spectroscopy demonstrated that these hexasacchrides share the common core saccharide structure GlcA beta 1-3GalNAc beta 1-4 GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3GalNAc with three, four, or five sulfate groups in different combinations. Six structures had the same sulfation profiles as those of the unsaturated hexasaccharides isolated from the same source after digestion with chondroitinase ABC (Sugahara et al., Eur. J. Biochem., 293, 871-880, 1996) and the other two have not been reported so far. In the new components, a D disaccharide unit, GlcA(2-sulfate)beta 1-3GalNAc(6-sulfate), characteristic of chondroitin sulfate D was arranged on the reducing side of an A disaccharide unit, GlcA beta 1-3GalNAc(4-sulfate), forming an unusual A-D tetrasaccharide sequence, GlcA beta 1-3GalNAc(4-sulfate)beta 1-4GlcA(2-sulfate)beta 1-3GalNAc(6-sulfate) which is known to be recognized by the monoclonal antibody MO225. These findings support the notion that the tetrasaccharide sequence, GlcA beta 1-3GalNAc(4-sulfate)beta 1-4GlcA beta 1-3GalNAc(6-sulfate) is included in the acceptor site of a hitherto unreported 2-O-sulfotransferase responsible for its synthesis. The sulfated hexasaccharides isolated in this study will be useful as authentic oligosaccharide probes and enzyme substrates in studies of sulfated glycosaminoglycans.
A New Concept for Multibranch Technology (1997)

Abstract Industry interest for multibranch wells has grown in the past few years thanks primarily to the new capabilities offered by quickly evolving drilling technologies. A wide range of applications. all aiming at improving reservoir production economics, has already been identified. However, multibranch wells have also created new challenges. Well construction. well control. as well as completion of the branches remain key issues yet to be satisfactorily addressed. A new concept of multibranch system design has been developed not only to address short term well construction issues (milling, drilling, and completing), but also to answer the needs of reservoir management during the life of the well. Input from over fifty oil companies was gathered to define this system's specifications. It was developed by a multidisciplinary team of specialists from major directional drilling, completion, drilling fluids, and cementing companies. This system is designed to provide a prefabricated sealed connection between the branches and the main trunk of the well. It will be functionally tested in a workshop prior to installation. Once installed in a well, the system provides ready to use sealed outlets which do not require window milling, nor does it rely on cement for pressure integrity, and it maintains full bore access below each branch. Other features include selective reentry ability in each branch at any stage of the life of the well, with minimal time spent for intervention Introduction A multibranch well is a vertical, deviated, or horizontal main conduit with two or more lateral conduits drilled at am depth, in any direction, and either horizontal or slit inclination. The main conduit may be an existing well (reentry) or a new well drilled specifically for the multibranch application. Multibranch wells provide opportunities for increased production rates at lower costs than single bore horizontal wells, and are particularly applicable for high cost and small fields. They will pennit a reduction in the surface construction requirements for wells; wellheads, surface and intermediate casing strings, and their corresponding costs. One of the greatest potential applications for multibranch wells will be in the development of deep water reservoirs where the number of wells and their surface construction items are commonly major driving factors in production system design and costs. Multibranch well technology is not a new technology. Since the early 1950s oil company operators have experimented with multibranch wells. These early wells were exclusively open hole sidetracked completions. Even today this is the most common example of multibranch well drilling as evidenced by the hundreds of multibranch wells being drilled in such areas as the Texas Austin Chalk and Canada.
The tau A0 allele in Parkinson's disease (2001)

Parkinson's disease (PD) is primarily an alpha-synucleinopathy, rather than a tauopathy, but there is evidence for an indirect association of tau with the pathogenetic process in PD. We therefore assessed the frequency in PD of the tau A0 allele, a dinucleotide repeat marker that has been associated with a sporadic tauopathy, progressive supranuclear palsy (PSP). We found the A0 allele to comprise 79.2% of 758 alleles from PD patients and 71.2% of 264 control alleles (P = 0.008). We also performed a meta-analysis of three previous reports, two of which failed to produce statistically significant results. Taken together, they also support a PD/A0 allelic association, even after correction for misdiagnosis of PSP as PD (P< 0.001). The A0/A0 genotype frequency in our patients (62.3%) did not differ significantly from that in controls (53.0%, P = 0.062), but the meta-analysis, even after correction for misdiagnosis, showed a significant result, with P = 0.002. The frequency of A0 allele and the A0/A0 genotype were compatible with Hardy-Weinberg equilibrium. The frequency of the A0 allele and the A0/A0 genotype in our patients with familial PD was not significantly greater than in those with sporadic PD. We conclude that the tau protein may play a small role in the pathogenesis of PD and that biochemical characterization of this role may suggest opportunities for PD prophylaxis.
Prostate cancer risk‐associated variants reported from genome‐wide association studies: Meta‐analysis and their contribution to genetic Variation (2010)

This study provides more stable OR estimates for PCa risk-associated SNPs, which is an important baseline for the effect of these SNPs in risk prediction. These SNPs explain a considerable proportion of genetic variance, however, the majority of genetic variance has yet to be explained.