gebhart/patrepeval huggingface dataset:
Backfilling Using System-Generated Predictions Rather than User Runtime Estimates (2007)

The most commonly used scheduling algorithm for parallel supercomputers is FCFS with backfilling, as originally introduced in the EASY scheduler. Backfilling means that short jobs are allowed to run ahead of their time provided they do not delay previously queued jobs (or at least the first queued job). However, predictions have not been incorporated into production schedulers, partially due to a misconception (that we resolve) claiming inaccuracy actually improves performance, but mainly because underprediction is technically unacceptable: users will not tolerate jobs being killed just because system predictions were too short. We solve this problem by divorcing kill-time from the runtime prediction and correcting predictions adaptively as needed if they are proved wrong. The end result is a surprisingly simple scheduler, which requires minimal deviations from current practices (e.g., using FCFS as the basis) and behaves exactly like EASY as far as users are concerned; nevertheless, it achieves significant improvements in performance, predictability, and accuracy. Notably, this is based on a very simple runtime predictor that just averages the runtimes of the last two jobs by the same user; counter intuitively, our results indicate that using recent data is more important than mining the history for similar jobs. All the techniques suggested in this paper can be used to enhance any backfilling algorithm and are not limited to EASY
Molecular ion battery: a rechargeable system without using any elemental ions as a charge carrier (2015)

Is it possible to exceed the lithium redox potential in electrochemical systems? It seems impossible to exceed the lithium potential because the redox potential of the elemental lithium is the lowest among all the elements, which contributes to the high voltage characteristics of the widely used lithium ion battery. However, it should be possible when we use a molecule-based ion which is not reduced even at the lithium potential in principle. Here we propose a new model system using a molecular electrolyte salt with polymer-based active materials in order to verify whether a molecular ion species serves as a charge carrier. Although the potential of the negative-electrode is not yet lower than that of lithium at present, this study reveals that a molecular ion can work as a charge carrier in a battery and the system is certainly a molecular ion-based "rocking chair" type battery.
Design, generation, and testing of mammalian expression modules that tag membrane proteins (2009)

The expression of mammalian membrane proteins in laboratory cell lines allows their biological functions to be characterized and carefully dissected. However, it is often difficult to design and generate effective antibodies for membrane proteins in the desired studies. As a result, expressed membrane proteins cannot be detected or characterized via common biochemical approaches such as western blotting, immunoprecipitation, or immunohistochemical analysis, and their cellular behaviors cannot be sufficiently investigated. To circumvent such roadblocks, we designed and generated two sets of expression modules that consist of sequences encoding for three essential components: (1) a signal peptide from human receptor for advanced glycation end products that targets the intended protein to the endoplasmic reticulum for cell surface expression; (2) an antigenic epitope tag that elicits specific antibody recognition; and (3) a series of restriction sites that facilitate subcloning of the target membrane protein. The modules were designed with the flexibility to change the epitope tag to suit the specific tagging needs. The modules were subcloned into expression vectors, and were successfully tested with both Type I and Type III human membrane proteins: the receptor for advanced glycation end products, the Toll-like receptor 4, and the angiotensin II receptor 1. These expressed membrane proteins are readily detected by western blotting, and are immunoprecipitated by antibodies to their relative epitope tags. Immunohistochemical and biochemical analyses also show that the expressed proteins are located at cell surface, and maintain their modifications and biological functions. Thus, the designed modules serve as an effective tool that facilitates biochemical studies of membrane proteins.
Development and Evaluation of a <i>Sarcocystis neurona</i> -Specific IgM Capture Enzyme-Linked Immunosorbent Assay (2006)

Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease of horses caused primarily by the protozoal parasite Sarcocystis neurona. Currently available antemortem diagnostic testing has low specificity. The hypothesis of this study was that serum and cerebrospinal fluid (CSF) of horses experimentally challenged with S neurona would have an increased S neurona-specific IgM (Sn-IgM) concentration after infection, as determined by an IgM capture enzyme linked immunoassay (ELISA). The ELISA was based on the S neurona low molecular weight protein SNUCD-1 antigen and the monoclonal antibody 2G5 labeled with horseradish peroxidase. The test was evaluated using serum and CSF from 12 horses experimentally infected with 1.5 million S neurona sporocysts and 16 horses experimentally infected with varying doses (100 to 100,000) of S neurona sporocysts, for which results of histopathologic examination of the central nervous system were available. For horses challenged with 1.5 million sporocysts, there was a significant increase in serum Sn-IgM concentrations compared with values before infection at weeks 2-6 after inoculation (P < .0001). For horses inoculated with lower doses of S neurona, there were significant increases in serum Sn-IgM concentration at various points in time after inoculation, depending on the challenge dose (P < .01). In addition, there was a significant increase between the CSF Sn-IgM concentrations before and after inoculation (P < .0001). These results support further evaluation of the assay as a diagnostic test during the acute phase of EPM.
Crystal structure of a cold-active protease (Pro21717) from the psychrophilic bacterium, Pseudoalteromonas arctica PAMC 21717, at 1.4 Å resolution: Structural adaptations to cold and functional analysis of a laundry detergent enzyme (2018)

Enzymes isolated from organisms found in cold habitats generally exhibit higher catalytic activity at low temperatures than their mesophilic homologs and are therefore known as cold-active enzymes. Cold-active proteases are very useful in a variety of biotechnological applications, particularly as active ingredients in laundry and dishwashing detergents, where they provide strong protein-degrading activity in cold water. We identified a cold-active protease (Pro21717) from a psychrophilic bacterium, Pseudoalteromonas arctica PAMC 21717, and determined the crystal structure of its catalytic domain (CD) at a resolution of 1.4 Å. The Pro21717-CD structure shows a conserved subtilisin-like fold with a typical catalytic triad (Asp185, His244, and Ser425) and contains four calcium ions and three disulfide bonds. Interestingly, we observed an unexpected electron density at the substrate-binding site from a co-purified peptide. Although the sequence of this peptide is unknown, analysis of the peptide-complexed structure nonetheless provides some indication of the substrate recognition and binding mode of Pro21717. Moreover, various parameters, including a wide substrate pocket size, an abundant active-site loop content, and a flexible structure provide potential explanations for the cold-adapted properties of Pro21717. In conclusion, this is first structural characterization of a cold-adapted subtilisin-like protease, and these findings provide a structural and functional basis for industrial applications of Pro21717 as a cold-active laundry or dishwashing detergent enzyme.
High-Throughput Cryopreservation of In Vivo-Derived Swine Embryos (2013)

Cryopreservation of swine embryos is inefficient. Our goal was to develop a non-invasive method for "relatively" high-throughput cryopreservation of in vivo-produced swine embryos. Since removal of the lipid droplets within early swine embryos improves cryosurvival we wanted to apply a technique of high osmolality treatment followed by centrifugation that was first developed for in vitro-produced swine embryos to in vivo-produced swine embryos. The first aim was to determine how sensitive the in vivo-produced zygote and 2-cell stage embryo was to various high osmolality conditions for a short duration. Culture for 6, 12 or 18 min at 300, 400 or 500 milliosmoles (mOsm) had no detectable affect on the resulting blastocyst stage embryos (number of inner cell mass nuclei, trophectoderm nuclei, total number of nuclei, ratio of the trophectoderm to inner cell mass nuclei or percent blastocyst). However there was an effect of gilt on each of these parameters. For the second aim we focused on 300 mOsm for 6 min, 400 mOsm for 12 min, 500 mOsm for 12 min, and 500 mOsm for 18 min. The embryos were centrifuged for the duration of high osmolality treatment, then cultured to the blastocyst stage and vitrified. After vitrification and thawing the 500 mOsm for 18 min had the highest percent re-expansion with no difference in the total number of nuclei. While requiring a different base culture medium than in vitro-produced embryos, in vivo-derived embryos also survive cryopreservation without damage to their zona pellucida.
Inorganic Arsenic Removal by Zero-Valent Iron (2000)

Zero-valent iron can be used to remove inorganic arsenic from aqueous solutions. The mechanism for arsenic removal appears to be a surface precipitation or adsorption of arsenic with iron. This mechanism differs significantly from the removal mechanisms of chlorinated hydrocarbons (reductive dechlorination) and chromium(VI) reduction accompanied by hydroxide precipitation. Arsenic removal efficiencies of greater than 95% are observed in laboratory and field-column studies. Arsenate is removed more effectively than arsenite; however, effective arsenite removal occurs even under anoxic conditions. The removal efficiency is related to the surface area or the type of iron used and improved over time, possibly due to pitting of the iron surface and increased surface area for sorption due to iron corrosion and ferrous iron adsorption/precipitation. Preliminary results indicate that arsenic is tightly bound to the iron filings, and only a small percentage is readily leached. This finding coupled with the results of field experiments and spectroscopic analysis (SEM/EDX and XPS) provide evidence that surface precipitation is the predominant removal mechanism. Key words: Arsenic removal; zero-valent iron
Abstract 3629: Overcoming macrophage immunosuppression in small cell lung cancer with high-affinity SIRPa variants (2014)

Abstract CD47 allows cancer cells to evade the immune system by signaling through SIRPa, an inhibitory receptor on macrophages. Therapies that block CD47 convert tumor-promoting macrophages to a tumoricidal state within the tumor microenvironment. We recently developed next-generation CD47 antagonists by engineering the extracellular domain of SIRPa. As single-domain polypeptides, these “high-affinity SIRPa variants” have an affinity for human CD47 (KD) as low as 11.1 pM, approximately 50,000-fold improved over wild-type SIRPa. By themselves, the high-affinity SIRPa variants are inert and therefore non-toxic in mouse and primate studies. However, when combined with tumor-specific antibodies, the high-affinity SIRPa variants act as immunotherapeutic adjuvants to antibody therapies by maximizing the ability of macrophages to destroy cancer cells. In our current study, we hypothesized these novel CD47-blocking agents could be applied to the treatment of small cell lung cancer (SCLC), a cancer with poor prognosis for which no clinically-approved antibodies or immunotherapies exist. We examined a panel of human SCLC samples and found all samples tested expressed high levels of CD47 on their surface. Using purified macrophages in vitro, we found that CD47-blocking therapies were able to induce macrophage phagocytosis of SCLC cell lines and primary patient samples. As a proof-of-concept, treatment of mice bearing primary SCLC tumors with CD47-blocking antibodies was able to inhibit tumor growth and significantly prolong survival. To identify novel SCLC antigens that can be targeted in combination with the high-affinity SIRPa variants, we screened SCLC samples by high-throughput flow cytometry using LEGENDScreen comprehensive antibody arrays. We identified several new and established therapeutic targets on the surface of SCLC cells, including CD99, CD56, CD166, CD326, and CD164. We identified antibodies to these antigens that could elicit macrophage phagocytosis in vitro, validating these antigens as targets for immune-based therapies. The ability of these antibodies to induce phagocytosis was dramatically enhanced when combined with the high-affinity SIRPa variants. Future studies will test these immunotherapeutic combinations in vivo against SCLC samples to develop novel therapeutic combinations for patients. We propose this strategy as a universal method to identify new tumor antigens and overcome macrophage immunosuppression within the tumor microenvironment. Citation Format: Kipp Weiskopf, Peter J. Schnorr, Nadine Jahchan, Aaron M. Ring, Roy L. Maute, Anne K. Volkmer, Jens-Peter Volkmer, Kenan C. Garcia, Julien Sage, Irving L. Weissman. Overcoming macrophage immunosuppression in small cell lung cancer with high-affinity SIRPa variants. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3629. doi:10.1158/1538-7445.AM2014-3629
Cavity Ring-Down Spectroscopy: An Overview (2002)

Cavity ring-down spectroscopy (CRDS) is a new technique for carrying out absorption measurements with increased sensitivity. Briefly, a pulse of radiation is injected into an optical cavity where it bounces back and forth between high-reflectivity mirrors. Some radiation leaks out an end mirror on each bounce, and the stored radiant energy inside the optical cavity decays exponentially (rings down) with time. When absorber molecules are present inside the optical cavity, the ring-down lifetime is shortened. A plot of the reciprocal of the ring-down lifetime (the ring-down rate) versus frequency gives the absorption spectrum.
Knockdown of Smad7 With a Specific Antisense Oligonucleotide Attenuates Colitis and Colitis-Driven Colonic Fibrosis in Mice (2018)

Attenuation of colitis with Smad7 antisense oligonucleotide limits development of colonic fibrosis.
Rational design and selection of bivalent peptide ligands of thrombin incorporating P4-P1 tetrapeptide sequences: from good substrates to potent inhibitors (2004)

The tetrapeptide Phe-Asn-Pro-Arg is a structurally optimized sequence for binding to the active site of thrombin. By conjugating this tetrapeptide or some variants to a C-terminal fragment of hirudin, we were able to generate a series of new bivalent inhibitors of thrombin containing only genetically encodable natural amino acids. We found that synergistic binding to both the active site and an exosite of thrombin can be enhanced through substitutions of amino acid residues at the P3 and P3' sites of the active-site directed sequence, Phe(P4)-Xaa(P3)-Pro(P2)-Arg(P1)-Pro(P1')-Gln(P2')-Yaa(P3'). Complementary to rational design, a phage library was constructed to explore further the residue requirements at the P4, P3 and P3' sites for bivalent and optimized two-site binding. Very significantly, panning of the phage library has led to thrombin-inhibitory peptides possessing strong anti-clotting activities in the low nanomolar range and yet interfering only partially the catalytic active site of thrombin. Modes of action of the newly discovered bivalent inhibitors are rationalized in light of the allosteric properties of thrombin, especially the interplay between the proteolytic action and regulatory binding occurring at thrombin surfaces remote from the catalytic active site.
DNA Synthesis Without Base Protection Using the Phosphoramidite Approach (2006)

In the strategy of DNA synthesis without base protection, a recent O-selective phosphorylation procedure known as the "activated phosphite method" is used to generate reactive phosphite intermediates from N-unprotected phosphoramidite building blocks. This new strategy proved to be advantageous over previous strategies because the cleavage of the N-P(III) bond, which can be formed by the significant phosphitylation of the nucleobase amino groups, can be omitted. The activated phosphite method provides an attractive route to high-throughput synthesis of DNA and the synthesis of alkali-labile modified DNAs such as oligonucleotides containing DNA lesions. This unit presents two convenient methods for the synthesis of N-unprotected deoxynucleoside 3'-phosphoramidite units and detailed procedures for automated synthesis of oligodeoxyribonucleotides from these phosphoramidite units.
Generating realistic datasets for deduplication analysis (2012)

Deduplication is a popular component of modern storage systems, with a wide variety of approaches. Unlike traditional storage systems, deduplication performance depends on data content as well as access patterns and meta-data characteristics. Most datasets that have been used to evaluate deduplication systems are either unrepresentative, or unavailable due to privacy issues, preventing easy comparison of competing algorithms. Understanding how both content and meta-data evolve is critical to the realistic evaluation of deduplication systems. We developed a generic model of file system changes based on properties measured on terabytes of real, diverse storage systems. Our model plugs into a generic framework for emulating file system changes. Building on observations from specific environments, the model can generate an initial file system followed by ongoing modifications that emulate the distribution of duplicates and file sizes, realistic changes to existing files, and file system growth. In our experiments we were able to generate a 4TB dataset within 13 hours on a machine with a single disk drive. The relative error of emulated parameters depends on the model size but remains within 15% of real-world observations. 1
hormone (FSH) and anti-Müllerian hormone (AMH) in female infertility (2010)

Background: Follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients. Methods: We investigated 366 consecutive infertility patients (350 reached IVF), excluding women with polycystic ovarian syndrome (PCOS). They were considered to have normal FSH and AMH if values fell within age-specific (as-) 95% confidence intervals (CI), and to suffer from diminished ovarian reserve (DOR) if FSH exceeded and/or AMH fell below those. The two hormones, thus, could be concordant (Group I), both normal (IA) or abnormal (IB), show normal AMH/abnormal FSH (Group II) or normal FSH/abnormal AMH (Group III). Oocyte yields, stratified for age categories, were then studied in each group as reflection of OR. Results: Oocyte yields significantly decreased from groups IA to II to III and IB. Predictive values of as-FSH/AMH patterns changed, however, at different ages. Except at very young and very old ages, normal as-AMH better predicted higher oocytes yields than normal as-FSH, though above age 42 years normal as-FSH predicts good oocyte yields even with abnormally low AMH. Under age 42 discrepancies between as- FSH and as-AMH remain similarly predictive of oocyte yields at all ages. Discussion: Concordances and discordances between as-FSH and as-AMH improve OR assessments and predictability of oocyte yields in IVF.
A phase I study of MEDI6383, an OX40 agonist, in adult patients with select advanced solid tumors. (2015)

TPS3093 Background: Enhancing T-cell function in cancer patients (pts) through T-cell co-stimulatory pathways such as OX40 has the potential to overcome cancer-induced immune suppression. MEDI6469, a human OX40 agonist murine antibody, administered for a single cycle in a phase I clinical study showed both an acceptable toxicity profile and regression of ≥ 1 metastatic lesion in 12 of 30 treated pts(Curti B, et al. Cancer Res 2013;73:7189–98). Humanized OX40 agonists are expected to have reduced immunogenicity relative to murine antibody, which may allow for repeat-dose administration, potentially enhancing biologic and antitumor activity. MEDI6383 is a human OX40 ligand fusion protein that in preclinical models initiates an intracellular signaling cascade to enhance T-cell survival, proliferation of T cells and macrophage lineage cells, and cytokine production. Methods: This is a phase I, multicenter, open-label study of MEDI6383 (NCT02221960) in adult pts with select recurrent or metastatic solid tumors. In the dose-escalation phase, sequential cohorts of pts will receive 1 of up to 6 dose levels (3+3 design) of MEDI6383 IV every 2 weeks for up to 48 weeks or until progressive disease (PD). In the dose-expansion phase, tumor-type specific cohorts will be treated at the MEDI6383 dose level and treatment schedule determined during dose escalation for up to 48 weeks or until PD. Pts who achieve a response and then have PD in follow-up may have 1 round of MEDI6383 retreatment. All pts will be followed for survival through end of study. The primary endpoint is safety and determination of the maximum tolerated dose; secondary endpoints are antitumor activity (objective response and disease control by immune-related RECIST, duration of response, progression-free survival, overall survival), pharmacokinetics, immunogenicity, and pharmacodynamics. Enrollment of up to 122 pts (42 pts, dose escalation; 80 pts, dose expansion) is ongoing. Clinical trial information: NCT02221960.
Laser Ablation Coupled to a Flowing Atmospheric Pressure Afterglow for Ambient Mass Spectral Imaging (2008)

A plasma-based ambient desorption/ionization mass spectrometry (ADI-MS) source was used to perform molecular mass spectral imaging. A small amount of sample material was ablated by focusing 266 nm laser light onto a spot. The resulting aerosol was transferred by a nitrogen stream to the flowing afterglow of a helium atmospheric pressure glow discharge ionization source; the ionized sample material was analyzed by a Leco Unique time-of-flight mass spectrometer. Two-dimensional mass spectral images were generated by scanning the laser beam across a sample surface. The total analysis time for a 6 mm (2) surface, which is limited by the washout of the ablation chamber, was less than 30 min. With this technique, a spatial resolution of approximately 20 microm has been achieved. Additionally, the laser ablation configuration was used to obtain depth information of over 2 mm with a resolution of approximately 40 microm. The combination of laser ablation with the flowing atmospheric pressure afterglow source was used to analyze several sample surfaces for a wide variety of analytes and with high sensitivity (LOD of 5 fmol for caffeine).