gebhart/patrepeval huggingface dataset:
Protein crystal growth. Growth kinetics for tetragonal lysozyme crystals. (1986)

A method for immobilizing protein crystals has been devised for determining face growth rates, and used to investigate the growth kinetics of hen egg white lysozyme crystals. Growth rates were determined at 22 degrees C in 0.1 M sodium acetate, 5% NaCl, pH 4.0, on the visually identified (110) face of tetragonal lysozyme crystals. Protein concentrations ranged from 13 to 57 mg/ml (saturation concentration = 1.7 mg/ml). Growth rate data were fit to the equation R = kappa sigma ri, where R = rate in cm/s; kappa = constant; sigma i = solute growth interface supersaturation; and r = rate dependence upon super-saturation, with the result that kappa = 0.146 X 10(-8) cm/s and r = 2.0. A model of the growth process was developed and the experimental data were used to determine the relative roles of transport and interfacial kinetics in the growth of this crystal. Values for the width of the boundary layer delta, the interfacial concentration Ci, and growth rate R were determined. The model may be used to extrapolate to other growth conditions. The relative role of transport and interfacial kinetics can be expressed by the coefficient gamma = (CB - Ci)/(CB - Cs), when CB is the bulk concentration and Cs the saturation. Values for gamma were found to range from much less than 0.1 for submicron-size crystals to approximately 0.15 for cm sizes. The results indicate that attachment or surface effects are rate-limiting in lysozyme crystal growth in Earth's gravity because solutal convection always provides more transport of solute than can be accommodated by the interface. In order to grow such crystals under transport limiting conditions, it would be necessary to suppress this solutal convection.
A Musculoskeletal Model of the Lower Limbs and its Application to Clinical Paediatric Orthopaedics (2012)

Articular cartilage accrual occurs predominantly during childhood and adolescence, with the magnitude, direction, and pattern of internal joint loads directing the cartilage growth.If any of these factors of the joint loading are abnormal, it can predispose these children to degenerative knee joint disease as an adult.To provide an estimate of the internal joint loads, a paediatricfocused, static optimization-based lower limb model was developed, compared to recorded sEMG, and analyzed for sensitivity to changes in ground reaction force and muscle attachment site.The model was found to provide consistent predictions of joint contact force predictions ranging from 0.01 to 0.35xBW with standard error of 8% to 17%, with the exception of left knee mediallateral shear at 108%.Muscle force predictions related well to sEMG, with the standard error ranging from 14% to 36%, except for gastrocnemius lateral at 104%.The model was sensitive to variations in the ground reaction force vector, with a maximum deviation of 0.11 xBW determined as a result of a 5% variation in GRF.The model was found to be sensitive to clinically relevant deviations in muscle attachment site.Maximum knee anterior shear was significantly changed (p < 0.05) with a 1cm posterior quadriceps insertion deviation, maximum lateral shear with a posterior semimembranosus deviation, and maximum medial shear with a posterior or medial quadriceps deviation.No deviations caused statistically significant changes in compression.Statistically significant change in joint contact force could not be predicted based on changes in muscle moment arm, but could be indirectly predicted by the predicted muscle forces.iii The model's uniform convergence and sensitivity to variations in input indicate that the model is sufficiently reliable and robust.This sensitivity suggests that the model is capable of adapting to altered loading conditions and musculoskeletal geometry, either due to deformity or corrective procedure.The model was therefore deemed to be a strong platform for developing clinically specific models for analyzing internal knee loads in a diverse paediatric population.As a great lady once put it during some trying times, "Things have a way of working out."There were a lot of ups and downs while completing my thesis, and I often had more on my plate than I needed to.Yet, I managed to make it through my Master's in (more or less) one piece, but only with the help of many people.And it is all of those people who deserve my thanks.To my future wife, thank you for being there to listen to me, no matter what, and for lending a hand when I needed it the most.To the one and only Dr. Moreside, thank you for always reminding me that it's just how the world works.To my supervisor, Dr. Pelland, thank you for pushing me to always do a little
Enhanced detection of microsatellite instability using pre-PCR elimination of wild-type DNA homo-polymers in tissue and liquid biopsies (2018)

Detection of microsatellite-instability in colonoscopy-obtained polyps, as well as in plasma-circulating DNA, is frequently confounded by sensitivity issues due to co-existing excessive amounts of wild-type DNA. While also an issue for point mutations, this is particularly problematic for microsatellite changes, due to the high false-positive artifacts generated by polymerase slippage (stutter-bands). Here, we describe a nuclease-based approach, NaME-PrO, that uses overlapping oligonucleotides to eliminate unaltered micro-satellites at the genomic DNA level, prior to PCR. By appropriate design of the overlapping oligonucleotides, NaME-PrO eliminates WT alleles in long single-base homopolymers ranging from 10 to 27 nucleotides in length, while sparing targets containing variable-length indels at any position within the homopolymer. We evaluated 5 MSI targets individually or simultaneously, NR27, NR21, NR24, BAT25 and BAT26 using DNA from cell-lines, biopsies and circulating-DNA from colorectal cancer patients. NaME-PrO enriched altered microsatellites and detected alterations down to 0.01% allelic-frequency using high-resolution-melting, improving detection sensitivity by 500-1000-fold relative to current HRM approaches. Capillary-electrophoresis also demonstrated enhanced sensitivity and enrichment of indels 1-16 bases long. We anticipate application of this highly-multiplex-able method either with standard 5-plex reactions in conjunction with HRM/capillary electrophoresis or massively-parallel-sequencing-based detection of MSI on numerous targets for sensitive MSI-detection.
Faster Secure Two-Party Computation Using Garbled Circuits (2011)

Secure two-party computation enables two parties to evaluate a function cooperatively without revealing to either party anything beyond the function&#39;s output. The garbled-circuit technique, a generic approach to secure two-party computation for semi-honest participants, was developed by Yao in the 1980s, but has been viewed as being of limited practical significance due to its inefficiency. We demonstrate several techniques for improving the running time and memory requirements of the garbled-circuit technique, resulting in an implementation of generic secure two-party computation that is significantly faster than any previously reported while also scaling to arbitrarily large circuits. We validate our approach by demonstrating secure computation of circuits with over 109 gates at a rate of roughly 10 microseconds per garbled gate, and showing order-of-magnitude improvements over the best previous privacy-preserving protocols for computing Hamming distance, Levenshtein distance, Smith-Waterman genome alignment, and AES.
Heparin and modified heparin inhibit complement activation in vivo (1992)

Heparin regulates C activity in vitro, but has not been examined for this activity in vivo. The present study investigated the ability of commercial heparin and derivatized (N-desulfated, N-acetylated) heparin (Hep-NAc) with greatly diminished anticoagulant activity to inhibit C activation in guinea pigs. Catheters were placed in the right atrium of guinea pigs and kept patent with frequent saline flushes. The next day, heparin, Hep-NAc, or saline was given and 2.5 min later cobra venom factor or saline was given. Blood was drawn at intervals and assayed for total hemolytic C, C3 hemolytic activity, free hemoglobin, and activated partial thromboplastin time. Total hemolytic C and C3 activity decreased less rapidly in heparin- and Hep-NAc-pretreated animals than in non-pretreated animals, indicating that both heparins inhibited C activation. Heparin and Hep-NAc also inhibited cobra venom factor-induced hemolysis. This study demonstrates that commercial heparin and modified heparin inhibit C activation in vivo. This represents an important step in the development of an oligosaccharide drug to regulate C activation.
Structural and Functional Neuroimaging in Alzheimers Disease: An Update (2002)

The field of neuroimaging has made several recent advances understanding Alzheimer's disease, a debilitating disease which affects approximately 4 million people in the United States [1]. Despite recent therapeutic advances, available treatments at present are aimed primarily at slowing progression of the disease rather than halting it completely or reversing its progression. Early detection of the disease has, therefore, been a major focus of a variety of neuroimaging techniques, including Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), and structural MRI. Recently, these techniques have also been found to be useful in monitoring cognitive and pathological progression of the disease, as well as monitoring response to clinical intervention treatment. A methodology review will be included here as well as a critical evaluation of the advantages and disadvantages of the various techniques.
The long view: a selective review of 40 years of Newcastle disease research (2012)

This review is written for the series celebrating the 40th year since the first issue of Avian Pathology. The aim of the authors was to cover the developments in Newcastle disease (ND) research over the last 40 years that they considered significant. During those 40 years there have been several panzootics of this serious disease in poultry and for the last 30 years there has been a continuing panzootic in domestic pigeons, which has spread to wild birds and poultry. The 40-year period began with worldwide outbreaks of severe ND, which served as an important impetus for ND research work. Although early work was concerned with controlling the disease, specifically by improving and developing new vaccines and vaccine regimens, even prior to the 1970s ND virus was seen as a useful laboratory virus for replication and virulence studies. This review covers the historical developments in the following areas: understanding the molecular basis of virulence; epidemiology and relatedness of different ND strains, both antigenically and genetically; the emergence of virulent strains and their relationship with viruses of low virulence; sequencing and understanding the viral genome and genes; the development of rapid molecular-based diagnostic tests; and the phylogeny and molecular taxonomy of ND virus. The authors suggest areas in which future research could or should be undertaken.
Adaptation of offline vertical selection predictions in the presence of user feedback (2009)

Web search results often integrate content from specialized corpora known as verticals. Given a query, one important aspect of aggregated search is the selection of relevant verticals from a set of candidate verticals. One drawback to previous approaches to vertical selection is that methods have not explicitly modeled user feedback. However, production search systems often record a variety of feedback information. In this paper, we present algorithms for vertical selection which adapt to user feedback. We evaluate algorithms using a novel simulator which models performance of a vertical selector situated in realistic query traffic.
Role of CD26/dipeptidyl peptidase IV in human T cell activation and function (2007)

CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5) activity that is expressed on numerous cell types and has a multitude of biological functions. CD26 role in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell (APC)-T-cell interaction. In this paper, we will review emerging data on CD26-mediated T-cell costimulation, suggesting that CD26 may be an appropriate therapeutic target for the treatment of immune disorders. However, the identity of its putative natural ligand had not yet been clearly elucidated. Recently, using protein engineering and proteomic approach, we have recently characterized the putative costimulatory ligand for CD26 in T-cells and the proximal signaling events directly associated with the cytoplasmic region of CD26 in CD26-associated T-cell costimulation, processes that are independent of the CD28 costimulatory pathway. Our work therefore presents novel findings that contribute to the area of T-cell costimulation and signal transduction.
Diverge-Merge Processor (DMP): Dynamic Predicated Execution of Complex Control-Flow Graphs Based on Frequently Executed Paths (2006)

This paper proposes a new processor architecture for handling hard-to-predict branches, the diverge-merge processor (DMP). The goal of this paradigm is to eliminate branch mispredictions due to hard-to-predict dynamic branches by dynamically predicating them without requiring ISA support for predicate registers and predicated instructions. To achieve this without incurring large hardware cost and complexity, the compiler provides control-flow information by hints and the processor dynamically predicates instructions only on frequently executed program paths. The key insight behind DMP is that most control-flow graphs look and behave like simple hammock (if-else) structures when only frequently executed paths in the graphs are considered. Therefore, DMP can dynamically predicate a much larger set of branches than simple hammock branches. Our evaluations show that DMP out performs a baseline processor with an aggressive branch predictor by 19.3% on average over SPEC integer 95 and 2000 benchmarks, through a reduction of 38% in pipeline flushes due to branch mispredictions, while consuming 9.0% less energy. We also compare DMP with previously proposed predication and dual-path/multipath execution paradigms in terms of performance, complexity, and energy consumption, and find that DMP is the highest performance and also the most energy-efficient design
Compiler-controlled memory (1998)

Optimizations aimed at reducing the impact of memory operations on execution speed have long concentrated on improving cache performance. These efforts achieve a. reasonable level of success. The primary limit on the compiler's ability to improve memory behavior is its imperfect knowledge about the run-time behavior of the program. The compiler cannot completely predict runtime access patterns.There is an exception to this rule. During the register allocation phase, the compiler often must insert substantial amounts of spill code ; that is, instructions that move values from registers to memory and back again. Because the compiler itself inserts these memory instructions, it has more knowledge about them than other memory operations in the program.Spill-code operations are disjoint from the memory manipulations required by the semantics of the program being compiled, and, indeed, the two can interfere in the cache. This paper proposes a hardware solution to the problem of increased spill costs---a small compiler-controlled memory (CCM) to hold spilled values. This small random-access memory can (and should) be placed in a distinct address space from the main memory hierarchy. The compiler can target spill instructions to use the CCM, moving most compiler-inserted memory traffic out of the pathway to main memory and eliminating any impact that those spill instructions would have on the state of the main memory hierarchy. Such memories already exist on some DSP microprocessors. Our techniques can be applied directly on those chips.This paper presents two compiler-based methods to exploit such a memory, along with experimental results showing that speedups from using CCM may be sizable. It shows that using the register allocation's coloring paradigm to assign spilled values to memory can greatly reduce the amount of memory required by a program.
Video-to-Audio Synchrony Monitoring and Correction (1988)

Contemporary practices in the transmission of network television programming have rendered traditional methods of restoring video-to-audio synchronization inadequate. Constantly changing transmission path lengths encountered in satellite transmissions make it impossible to predict accurately the amount of delay that will be introduced by video processing, and other kinds of processing may introduce further unknown delay times. A new method of using encoded audio to determine relative time differences between audio and video can fully automate and guarantee proper video-to-audio synchronization at the receiving station. This correction can be made at any point in the system and does not require any knowledge of the amount of delay that may have been accumulated along the way.
Effect of a computer-aided diagnosis scheme on radiologists' performance in detection of lung nodules on radiographs. (1996)

The CAD scheme can assist radiologists in the detection of lung nodules on chest radiographs.
Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system. (1993)

We report the molecular cloning and characterization of two structurally related putative receptor tyrosine kinases, encoded by distinct genes (tie-1 and tie-2) on mouse chromosome 4. Both tie-1 and tie-2 encode receptor proteins possessing unique multiple extracellular domains: two immunoglobulin-like loop domains flanking three epidermal growth factor repeats followed by three fibronectin-type III repeats. Both genes are expressed in early embryonic vascular system and in maternal decidual vascular endothelial cells, where the vasculature undergoes an active angiogenesis. tie-2, but not tie-1, expression was also detected in extraembryonic mesoderm of the amnion. tie-1, but not tie-2, is expressed in an acute myelogenic cell line in vitro. tie-1 and tie-2 may form another class within the receptor tyrosine kinase gene family, and further characterization of these genes and identification of their putative ligands should define the nature of the signal-transduction cascades underlying early vascular system development, as well as their differential roles in mesodermal cells of the amniotic and myeloid lineages.
Crystallographic Analysis of Bacterial Signal Peptidase in Ternary Complex with Arylomycin A2 and a β-Sultam Inhibitor (2009)

Bacterial type I signal peptidase (SPase I), an essential membrane-bound endopeptidase with a unique Ser/Lys dyad mechanism, is being investigated as a potential novel antibiotic target. We present here binding and inhibition assays along with crystallographic data that shows that the lipohexapeptide-based natural product arylomycin A2 and the morpholino-beta-sultam derivative (BAL0019193) inhibit SPase I by binding to non-overlapping subsites near the catalytic center. The 2.0 A resolution crystal structure of the soluble catalytic domain of Escherichia coli SPase I (SPase I Delta2-75) in ternary complex with arylomycin A2 and BAL0019193 reveals the position of BAL0019193 adjacent to arylomycin A2 within the SPase I binding site. BAL0019193 binds in a noncovalent manner in close proximity to SPase I residues Ser88, Ser90, Lys145, Asn277, Ala279, and Glu307, as well as atom O45 of arylomycin A2. The binding mode of arylomycin A2 in this 2.0 A resolution ternary complex is compared to that seen in the previous 2.5 A resolution arylomycin A2-SPase cocrystal structure. This work contributes to our understanding of SPase I inhibitor/substrate recognition and should prove helpful in the further development of novel antibiotics based on the inhibition of SPase I.
T helper cell epitope of rabies virus nucleoprotein defined by tri‐ and tetrapeptides (1991)

T cell clones and subsequently hybridomas were generated from rabies virus-immune C3H/He mice to an immunodominant epitope of the viral nucleoprotein, termed 31D, that had previously been identified by a 15-amino acid-long synthetic peptide. T cells to this epitope that by phenotypical and functional characteristics belonged to the T helper cell subset were shown to respond to most rabies and rabies-related viruses. In order to define the minimal sequence needed to elicit a response from 31D-specific T cell clones or hybridomas, a number of peptides of varied lengths, i.e. 3-32 amino acids long, were tested. The ability of the peptides to induce a response was inversely correlated in their lengths, i.e., short peptides (3-5 amino acids long) had to be used at 10(6) times higher concentrations as compared to long peptides (15 or 32 amino acids long). Conversely, the specificity of the T cell response was directly correlated to the length of the peptides, i.e., while the response to 15-amino acid-long peptides exhibited a high degree of specificity, the response to 3- to 5-amino acid-long peptides showed a high degree of flexibility. The long as well as the short peptides had to be presented in association with I-Ek. We speculate that in this system the T cell receptor interacts predominantly with a peptide-induced modification of the I-Ek molecule.
A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. (2001)

The treatment of advanced neuroblastoma (NB) or Ewing's sarcoma (ES) is one of the major challenges in pediatric oncology. Both malignancies are refractory to conventional therapies and have an extremely poor prognosis. High-dose myeloablative radiochemotherapy with autologous bone marrow or peripheral blood stem cell rescue is one of the most aggressive treatments attempted for these diseases but is often undermined by residual tumor cells contaminating the graft. Thus, in this approach, purging of tumor cells from the graft is key to the prevention of relapse after transplantation. We investigated a novel approach to eliminate tumor cells from the bone marrow or peripheral blood stem cell graft without causing stem cell damage through the use of a conditionally replicative adenovirus (Ad). ES and NB are sensitive to Ad infection, and advanced NBs express a high level of the growth/differentiation factor midkine (MK). We confirmed in this study that ES cell lines (SK-ES-1 and RD-ES) are also sensitive to Ad infection and express high levels of MK. In contrast, CD34+ stem cells are refractory to Ad infection and express very little MK. A conditionally replicative Ad in which the expression of E1 is controlled by the MK promoter achieved good levels of viral replication in NB or ES and induced remarkable tumor cell killing. On the other hand, this virus caused no damage to CD34+ cells even after 3 h of infection at a dose of 1000 multiplicity of infection. We concluded that application of this replication-competent Ad to hematopoietic grafts could be a simple but effective procedure to achieve complete tumor cell purging.