gebhart/patrepeval huggingface dataset:
Simple Procedure for the Isolation of Mouse Interferon-Beta (1983)

We report a simple procedure for the isolation of a mouse interferon beta (beta IFN) from Ehrlich ascites tumor cells infected with Newcastle disease virus. The procedure consists of four chromatographic steps (two on controlled pore glass, one on CM-Sephadex, and one on phosphocellulose) with stepwise elution. The product purified is a 35-40 kD beta IFN with a specific activity of 10(9) units/mg protein.
In-vivo strain measurement for surgically repaired Achilles tendon under isometric contraction using real-time ultrasound imaging (2011)

2010-2011 > Academic research: refereed > Publication in refereed journal
Statically-directed dynamic automated test generation (2011)

We present a new technique for exploiting static analysis to guide dynamic automated test generation for binary programs, prioritizing the paths to be explored. Our technique is a three-stage process, which alternates dynamic and static analysis. In the first stage, we run dynamic analysis with a small number of seed tests to resolve indirect jumps in the binary code and build a visibly pushdown automaton (VPA) reflecting the global control-flow of the program. Further, we augment the computed VPA with statically computable jumps not executed by the seed tests. In the second stage, we apply static analysis to the inferred automaton to find potential vulnerabilities, i.e., targets for the dynamic analysis. In the third stage, we use the results of the prior phases to assign weights to VPA edges. Our symbolic-execution based automated test generation tool then uses the weighted shortest-path lengths in the VPA to direct its exploration to the target potential vulnerabilities. Preliminary experiments on a suite of benchmarks extracted from real applications show that static analysis allows exploration to reach vulnerabilities it otherwise would not, and the generated test inputs prove that the static warnings indicate true positives.
Efficacy of Modafinil on Fatigue and Excessive Daytime Sleepiness Associated with Neurological Disorders: A Systematic Review and Meta-Analysis (2013)

Existing trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.
Synthesis of the Dipotassium Salts of Methyl α-D-Mannopyranoside 6-Phosphorothioate and D-Mannose 6-Phosphorothioate (1996)

Dipotassium methyl α-D-mannopyranoside 6-phosphorothioate (4) and dipotassium D-mannose 6-phosphorothioate (7) have been prepared from per-O-trimethylsilyl derivatives of methyl α-D-mannopyranoside and D-mannopyranose, respectively, through reaction sequences involving selective cleavage in the pyranoside ether, and selective replacement in the pyranose ether, of a 6-O-trimethylsilyl group.
Zeus lightens, thunders, rains, etc (2010)

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Profiling, what-if analysis, and cost-based optimization of MapReduce programs (2011)

MapReduce has emerged as a viable competitor to database systems in big data analytics. MapReduce programs are being written for a wide variety of application domains including business data processing, text analysis, natural language processing, Web graph and social network analysis, and computational science. However, MapReduce systems lack a feature that has been key to the historical success of database systems, namely, cost-based optimization. A major challenge here is that, to the MapReduce system, a program consists of black-box map and reduce functions written in some programming language like C++, Java, Python, or Ruby. We introduce, to our knowledge, the first Cost-based Optimizer for simple to arbitrarily complex MapReduce programs. We focus on the optimization opportunities presented by the large space of configuration parameters for these programs. We also introduce a Profiler to collect detailed statistical information from unmodified MapReduce programs, and a What-if Engine for fine-grained cost estimation. All components have been prototyped for the popular Hadoop MapReduce system. The effectiveness of each component is demonstrated through a comprehensive evaluation using representative MapReduce programs from various application domains.
An Oxazaphospholidine Approach for the Stereocontrolled Synthesis of Oligonucleoside Phosphorothioates (2003)

The stereocontrolled synthesis of oligodeoxyribonucleoside phosphorothioates (PS-ODNs) using nucleoside 3'-O-oxazaphospholidine derivatives as monomer units is described. 2-Chloro-1,3,2-oxazaphospholidine derivatives were prepared from six kinds of enantiopure 1,2-amino alcohols and used for the phosphitylation reactions of 5'-O-protected nucleosides. A detailed study of these reactions revealed that the diastereoselectivity of the reaction depended on the structure of the enantiopure 1,2-amino alcohol, the reaction temperature, and the amine used as a scavenger of HCl. In addition, ab initio molecular orbital calculations for the 2-chlorooxazaphospholidine derivatives were carried out to elucidate the mechanism of these diastereoselective phosphitylation reactions. The LUMO of the 2-chloro-5-phenyloxazaphospholidine derivatives on the phosphorus atom was found to be almost orthogonal to the P-Cl bond. This LUMO may be involved in the phosphitylation reactions with predominant retention of the P-configuration. A series of dialkyl(cyanomethyl)ammonium salts were developed and used as activators for the condensation reactions of the diastereopure nucleoside 3'-O-oxazaphospholidines with 3'-O-protected nucleosides. In the presence of the new activators, the reactions proceeded rapidly to give the corresponding dinucleoside phosphite triesters. The diastereoselectivity of the condensation reaction did not depend on the counteranion but on the structure of the dialkyl(cyanomethyl)amine. In the presence of the activator, which consists of a relatively small dialkyl(cyanomethyl)amine, the condensation proceeded with excellent diastereoselectivity. After sulfurization and deprotection, diastereopure (R(p))- and (S(p))-dinucleoside phosphorothioates were obtained in excellent yields. The present methodology was also applied to the solid-phase synthesis of stereoregulated PS-ODNs. all-(R(p))-[T(PS)](3)T, all-(S(p))-[T(PS)](3)T, all-(R(p))-d[G(PS)A(PS)C(PS)]T, and all-(R(p))-[T(PS)](9)T were synthesized on a highly cross-linked polystyrene resin.
A New K+ Channel β Subunit to Specifically Enhance Kv2.2 (CDRK) Expression (1996)

Cloned K+ channel beta subunits are hydrophilic proteins which associate to pore-forming alpha subunits of the Shaker subfamily. The resulting alphabeta heteromultimers K+ channels have inactivation kinetics significantly more rapid than those of the corresponding alpha homomultimers. This paper reports the cloning and the brain localization of mKvbeta4 (m for mouse), a new beta subunit. This new beta subunit is highly expressed in the nervous system but is also present in other tissues such as kidney. In contrast with other beta subunits, coexpression of the mKvbeta4 subunit with alpha subunits of Shaker-type K+ channel does not modify the kinetic properties or voltage-dependence of these channels in Xenopus oocytes. Instead, mKvbeta4 associates to Kv2.2 (CDRK), a Shab K+ channel, to specifically enhance (a factor of up to 6) its expression level without changing its elementary conductance or kinetics. It is without effect on another closely related Shab K+ channel Kv2.1 (DRK1). Chimeras between Kv2.1 and Kv2. 2 indicate that the COOH-terminal end of the Kv2.2 protein is essential for its mKvbeta4 sensitivity. The functional results associated with the observation of the co-localization of mKvbeta4 and Kv2.2 transcripts in most brain areas strongly suggest that both subunits interact in vivo to form a slowly-inactivating K+ channel. A chaperone-like effect of mKvbeta4 seems to permit the integration of a larger number of Kv2.2 channels at the plasma membrane.
Store Atomicity for Transactional Memory (2007)

We extend the notion of Store Atomicity [Arvind and Jan-Willem Maessen. Memory model = instruction reordering + store atomicity. In ISCA '06: Proceedings of the 33rd annual International Symposium on Computer Architecture, 2006] to a system with atomic transactional memory. This gives a fine-grained graph-based framework for defining and reasoning about transactional memory consistency. The memory model is defined in terms of thread-local Instruction Reordering axioms and Store Atomicity, which describes inter-thread communication via memory. A memory model with Store Atomicity is serializable: there is a unique global interleaving of all operations which respects the reordering rules and serializes all the operations in a transaction together. We extend Store Atomicity to capture this ordering requirement by requiring dependencies which cross a transaction boundary to point in to the initiating instruction or out from the committing instruction. We sketch a weaker definition of transactional serialization which accounts for the ability to interleave transactional operations which touch disjoint memory. We give a procedure for enumerating the behaviors of a transactional program—noting that a safe enumeration procedure permits only one transaction to read from memory at a time. We show that more realistic models of transactional execution require speculative execution. We define the conditions under which speculation must be rolled back, and give criteria to identify which instructions must be rolled back in these cases.
Improved Clinical Outcome in Indolent B-Cell Lymphoma Patients Vaccinated with Autologous Tumor Cells Experiencing Immunogenic Death (2010)

Increasing evidence argues that the success of an anticancer treatment may rely on immunoadjuvant side effects including the induction of immunogenic tumor cell death. Based on the assumption that this death mechanism is a similar prerequisite for the efficacy of an active immunotherapy using killed tumor cells, we examined a vaccination strategy using dendritic cells (DC) loaded with apoptotic and necrotic cell bodies derived from autologous tumors. Using this approach, clinical and immunologic responses were achieved in 6 of 18 patients with relapsed indolent non-Hodgkin's lymphoma (NHL). The present report illustrates an impaired ability of the neoplastic cells used to vaccinate nonresponders to undergo immunogenic death on exposure to a cell death protocol based on heat shock, γ-ray, and UVC ray. Interestingly, when compared with doxorubicin, this treatment increased surface translocation of calreticulin and cellular release of high-mobility group box 1 and ATP in histologically distinct NHL cell lines. In contrast, treated lymphoma cells from responders displayed higher amounts of calreticulin and heat shock protein 90 (HSP90) compared with those from nonresponders and boosted the production of specific antibodies when loaded into DCs for vaccination. Accordingly, the extent of calreticulin and HSP90 surface expression in the DC antigenic cargo was significantly associated with the clinical and immunologic responses achieved. Our results indicate that a positive clinical effect is obtained when immunogenically killed autologous neoplastic cells are used for the generation of a DC-based vaccine. Therapeutic improvements may thus be accomplished by circumventing the tumor-impaired ability to undergo immunogenic death and prime the antitumor immune response.
Hsa‐miR‐125b suppresses bladder cancer development by down‐regulating oncogene SIRT7 and oncogenic long non‐coding RNA MALAT1 (2013)

MicroRNAs mainly inhibit coding genes and long non-coding RNA expression. Here, we report that hsa-miR-125b and oncogene SIRT7/oncogenic long non-coding RNA MALAT1 were inversely expressed in bladder cancer. Hsa-miR-125b mimic down-regulated, whereas hsa-miR-125b inhibitor up-regulated the expression of SIRT7 and MALAT1. Binding sites were confirmed between hsa-miR-125b and SIRT7/MALAT1. Up-regulation of hsa-miR-125b or down-regulation of SIRT7 inhibited proliferation, motility and increased apoptosis. The effects of up-regulation of hsa-miR-125b were similar to that of silencing MALAT1 in bladder cancer as we had previously described. These data suggest that hsa-miR-125b suppresses bladder cancer development via inhibiting SIRT7 and MALAT1.
Topical Treatments for Onychomycosis (2003)

Topical treatment of onychomycosis, in contrast to systemic oral therapy, allows the patient to apply medication directly to the affected area, thereby decreasing the potential for adverse events and drug interactions. Historically, several topical antifungal agents have been used in the treatment of onychomycosis; however, the evidence for their effectiveness is based on very limited data or anecdotal reports. Recently, the development of new, effective topical agents has renewed interest in this form of therapy. As clinical experience with newer topical agents expands, they may be found to be an effective option for the treatment of onychomycosis.
Porcine Xenografts in Parkinson's Disease and Huntington's Disease Patients: Preliminary Results (2000)

The observation that fetal neurons are able to survive and function when transplanted into the adult brain fostered the development of cellular therapy as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demonstrated to be efficacious in patients with Parkinson's disease after transplantation of human fetal neurons. The use of human fetal tissue is limited by ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a reasonable source of fetal neuronal tissue because of their brain size, large litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafted unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are being evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale "off" state scores in 10 PD patients assessed 12 months after unilateral striatal transplantation of 12 million fetal porcine ventral mesencephalic (VM) cells. Several patients have improved more than 30%. In a single autopsied PD patient some porcine fetal VM cells were observed to survive 7 months after transplantation. Twelve HD patients have shown a favorable safety profile and no change in total functional capacity score 1 year after unilateral striatal placement of up to 24 million fetal porcine striatal cells. Xenotransplantation of fetal porcine neurons is a promising approach to delivery of healthy neurons to the CNS. The major challenges to the successful use of xenogeneic fetal neuronal cells in neurodegenerative diseases appear to be minimizing immune-mediated rejection, management of the risk of xenotic (cross-species) infections, and the accurate assessment of clinical outcome of diseases that are slowly progressive.
Calcium‐Induced Changes in Annexin V Behaviour in Solution as Seen by Proton NMR Spectroscopy (1994)

The behaviour of human annexin V in the presence of calcium was studied by NMR. We observe the formation of well defined dimers, as well as a change in the local dynamics of one His side chain. We assign the observed changes to either His98 or His267 residues and conclude that they could be related either to the hinge-bending motion reported from crystal structures, or to a local side chain rearrangement within the calcium-binding loops concerned. Dimerization was also confirmed by a small-angle neutron-scattering experiment. Under the experimental conditions used, we do not observe the conformational change involving Trp187 seen in previous studies, which occurs at higher relative calcium concentrations.
Effect of ZnS shell thickness on the phonon spectra in CdSe quantum dots (2003)

The evolution of the optical phonon spectra of colloidal core/shell CdSe/ZnS quantum dots with an increase of the shell thickness from 0.5 to 3.4 monolayers has been studied by resonant Raman spectroscopy. The results obtained suggest that the ZnS shell changes its structure from amorphous to partly crystalline as the thickness increases. Simultaneously, an increase in Raman scattering by surface (core/shell interface) phonons and the redshift of the corresponding phonon band have been observed and assigned to variations in the shell structure. The disorder present in the shell provides a major contribution to the line shape of the Raman spectra at higher ZnS coverage. A method to control the quality of quantum dots based on Raman spectroscopy is proposed.
Learning the High-Dimensional Immunogenomic Features That Predict Public and Private Antibody Repertoires (2017)

Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which may be defined as Ab or TCR clonal sequences shared across individuals. It has remained unclear whether public clones possess predictable sequence features that differentiate them from private clones, which are believed to be generated largely stochastically. This knowledge gap represents a lack of insight into the shaping of immune repertoire diversity. Leveraging a machine learning approach capable of capturing the high-dimensional compositional information of each clonal sequence (defined by CDR3), we detected predictive public clone and private clone-specific immunogenomic differences concentrated in CDR3's N1-D-N2 region, which allowed the prediction of public and private status with 80% accuracy in humans and mice. Our results unexpectedly demonstrate that public, as well as private, clones possess predictable high-dimensional immunogenomic features. Our support vector machine model could be trained effectively on large published datasets (3 million clonal sequences) and was sufficiently robust for public clone prediction across individuals and studies prepared with different library preparation and high-throughput sequencing protocols. In summary, we have uncovered the existence of high-dimensional immunogenomic rules that shape immune repertoire diversity in a predictable fashion. Our approach may pave the way for the construction of a comprehensive atlas of public mouse and human immune repertoires with potential applications in rational vaccine design and immunotherapeutics.
MK‐801 induces apoptotic neuronal death in the rat retrosplenial cortex: Prevention by cycloheximide and R(−)‐2‐Hexyl‐N‐ Methylpropargylamine (1996)

MK-801 is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which can prevent excitatory neuronal death. At higher concentrations, however, it can also induce neuronal death in the limbic system. This MK-801-induced selective neurotoxicity has been proposed as an animal model for dementia and psychosis. We have investigated the effects of the protein synthesis inhibitor cycloheximide and the neurorescue agent 2-hexyl-N-methylpropargylamine [R(−)-2HxMP] on MK-801-induced neuronal death in the retrosplenial cortex in the rat. Cycloheximide [2 mg/kg, subcutaneously (sc)] administered either 1 hr before, or after, injection of MK-801 (5 mg/kg, sc) prevented almost completely neuronal shrinkage and nuclear condensation of the granular retrosplenial cortex as assessed by hematoxylin-eosin staining. The results suggest that the MK-801-induced neuronal death was apoptotic. This neurorescue effect by cycloheximide was time dependent: after 4 hr the effect was reduced to about 50% and by 8 hr had disappeared. R(−)-2HxMP (0.25 mg/kg, sc), which does not inhibit protein synthesis in vitro, was also found to be effective at preventing MK-801-induced neuronal death. © 1996 Wiley-Liss, Inc.
Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains. (1991)

Recombinant calreticulin and discrete domains of calreticulin were expressed in Escherichia coli, using the glutathione S-transferase fusion protein system, and their Ca2+ binding properties were determined. Native calreticulin bound 1 mol of Ca2+/mol of protein with high affinity, and also bound approximately 20 mol of Ca2+/mol of protein with low affinity. Both Ca2+ binding sites were present in the recombinant calreticulin indicating that proper folding of the protein was achieved using this system. Calreticulin is structurally divided into three distinct domains: the N-domain encompassing the first 200 residues; the P-domain which is enriched in proline residues (residue 187-317); and the C-domain which covers the carboxyl-terminal quarter of the protein (residues 310-401), and contains a high concentration of acidic residues. These domains were expressed in E. coli, isolated, and purified, and their Ca2+ binding properties were analyzed. The C-domain bound approximately 18 mol of Ca2+/mol of protein with a dissociation constant of approximately 2 mM. The P-domain bound approximately 0.6-1 mol of Ca2+/mol of protein with a dissociation constant of approximately 10 microM. The P-domain and the C-domain, when expressed together as the P+C-domain, bound Ca2+ with both high affinity and low affinity, reminiscent of both full length recombinant calreticulin and native calreticulin. In contrast the N-domain, did not bind any detectable amount of 45Ca2+. We conclude that calreticulin has two quite distinct types of Ca2+ binding sites, and that these sites are in different structural regions of the molecule. The P-domain binds Ca2+ with high affinity and low capacity, whereas the C-domain binds Ca2+ with low affinity and high capacity.
The desferrithiocin (DFT) class of iron chelators: potential as antineoplastic agents. (2002)

Iron (Fe) is essential for the proliferation of cancer cells. A subgroup of the orthosubstituted phenolate class of Fe chelators, desferrithiocin [2-(3'-hydroxypyrid-2'-yl)4-methyl-delta2-thiazoline-4(S)-carboxylic acid; DFT] and its analogues, have potential application in short-term chemotherapy for cancer by Fe deprivation. Their effects on cell proliferation, cell cycle progression, Fe uptake and toxicity were therefore examined in adult and fetal rat and human hepatocellular carcinoma (HCC) cell lines, as well as in normal cells. DFT was more active than desferrioxamine, in clinical trials as an antineoplastic agent, consistently inhibiting cell proliferation in all cell lines (IC50 = 40 microM). 2-(2'-hydroxyphenyl-2'-yl)-delta2-thiazoline-4(S)-carboxylic acid was the most active analogue (IC50 = 55-90 microM). Inhibition was affected by chelator concentration and ability to prevent Fe uptake. The fetal-cell-derived HCC was more susceptible than adult HCC. Structure-activity studies revealed that thiazol methyl deletion greatly diminished antiproliferative activity of the chelators but stereochemical orientation of COOH around C4 had no effect. Removal of the N from the pyridine ring restored antiproliferative activity. Chelators inhibited DNA synthesis in the S phase. The chelators at their IC50 concentration had little or no effect on Fe uptake in normal cells. This apparent selectivity of these chelators for cancer cells, coupled with their high activity, suggests that further investigation is warranted.