gebhart/patrepeval huggingface dataset:
NoScope (2017)

Recent advances in computer vision---in the form of deep neural networks---have made it possible to query increasing volumes of video data with high accuracy. However, neural network inference is computationally expensive at scale: applying a state-of-the-art object detector in real time (i.e., 30+ frames per second) to a single video requires a $4000 GPU. In response, we present N o S cope , a system for querying videos that can reduce the cost of neural network video analysis by up to three orders of magnitude via inference-optimized model search. Given a target video, object to detect, and reference neural network, N o S cope automatically searches for and trains a sequence, or cascade, of models that preserves the accuracy of the reference network but is specialized to the target video and are therefore far less computationally expensive. N o S cope cascades two types of models: specialized models that forego the full generality of the reference model but faithfully mimic its behavior for the target video and object; and difference detectors that highlight temporal differences across frames. We show that the optimal cascade architecture differs across videos and objects, so N o S cope uses an efficient cost-based optimizer to search across models and cascades. With this approach, N o S cope achieves two to three order of magnitude speed-ups (265-15,500x real-time) on binary classification tasks over fixed-angle webcam and surveillance video while maintaining accuracy within 1--5% of state-of-the-art neural networks.
Market Discipline of Canadian Banks' Letters of Credit Activities: An Empirical Examination (2002)

While the motivation and riskiness of US off-balance sheet banking activities have been studied both theoretically and empirically, no such study has been found dealing with Canadian off-balance sheet banking activities, although such activities are numerically huge, and growing larger each year. This article provides support for a market discipline hypothesis of Canadian bank letters of credit activities by employing several market measures of risk from one-factor and multi-factor models, and an implied asset volatility from the option-pricing model. Furthermore, it examines both price and quantity response of off-balance sheet activities in the Canadian banking market by employing a tobit analysis to assess the robustness of our conclusions about market discipline. The results indicate that various market measures of risk and letters of credit are negatively related. Moreover, banks with greater portfolio risk measured in terms of equity and asset risk, high leverage and interest rate risk are less likely to issue letters of credit.
Dengue Human Infection Model Performance Parameters (2014)

Dengue is a global health problem and of concern to travelers and deploying military personnel with development and licensure of an effective tetravalent dengue vaccine a public health priority. The dengue viruses (DENVs) are mosquito-borne flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests across a clinical spectrum with severe disease characterized by intravascular volume depletion and hemorrhage. DENV illness results from a complex interaction of viral properties and host immune responses. Dengue vaccine development efforts are challenged by immunologic complexity, lack of an adequate animal model of disease, absence of an immune correlate of protection, and only partially informative immunogenicity assays. A dengue human infection model (DHIM) will be an essential tool in developing potential dengue vaccines or antivirals. The potential performance parameters needed for a DHIM to support vaccine or antiviral candidates are discussed.
Quantitative Detection of Borrelia burgdorferi by Real-Time PCR (1999)

ABSTRACT Currently, no easy and reliable methods allowing for the quantification of Borrelia burgdorferi in tissues of infected humans or animals are available. Due to the lack of suitable assays to detect B. burgdorferi CFU and the qualitative nature of the currently performed PCR assays, we decided to exploit the recently developed real-time PCR. This technology measures the release of fluorescent oligonucleotides during the PCR. Flagellin of B. burgdorferi was chosen as the target sequence. A linear quantitative detection range of 5 logs with a calculated detection limit of one to three spirochetes per assay reaction mixture was observed. The fact that no signals were obtained with closely related organisms such as Borrelia hermsii argues for a high specificity of this newly developed method. A similar method was developed to quantify mouse actin genomic sequences to allow for the standardization of spirochete load. The specificity and sensitivity of the B. burgdorferi and the actin real-time PCR were not altered when samples were spiked with mouse cells or spirochetes, respectively. To evaluate the applicability of the real-time PCR, we used the mouse model of Lyme disease. The fate of B. burgdorferi was monitored in different tissues from inbred mice and from mice treated with antibiotics. Susceptible C3H/HeJ mice had markedly higher burdens of bacterial DNA than resistant BALB/c mice, and penicillin G treatment significantly reduced the numbers of spirochetes. Since these results show a close correlation between clinical symptoms and bacterial burden of tissues, we are currently analyzing human biopsy specimens to evaluate the real-time PCR in a diagnostic setting.
INDEPENDENT COMPONENT ANALYSIS FOR EEG SOURCE LOCALIZATION IN REALISTIC HEAD MODELS (1999)

A pervasive problem in neuroscience is determining which regions of the brain are active, given voltage measurements at the scalp. If accurate solutions to such problems could be obtained, neurologists would gain non-invasive access to patient-specific cortical activity. Access to such data would ultimately increase the number of patients who could be e#ectively treated for neural pathologies such as multi-focal epilepsy. However, estimating the location and distribution of electric current source within the brain from electroencephalographic (EEG) recordings is an ill-posed problem. Specifically, there is no unique solution and solutions do not depend continuously on the data. The ill-posedness of the problem makes finding the correct solution a challenging analytic and computational problem. In this paper we consider a spatio-temporal method for sources localization, taking advantage of the entire EEG time series to reduce the configuration space we must evaluate. The EEG data is fir...
Matrix metalloproteinases in subjects with type 1 diabetes (2009)

Our MMP analysis of serum from a limited number of patients with type 1 diabetes suggest that such analysis is potentially useful as markers in studies of people at risk of progression to chronic kidney disease.
Evolution of Amino Acid Frequencies in Proteins Over Deep Time: Inferred Order of Introduction of Amino Acids into the Genetic Code (2002)

To understand more fully how amino acid composition of proteins has changed over the course of evolution, a method has been developed for estimating the composition of proteins in an ancestral genome. Estimates are based upon the composition of conserved residues in descendant sequences and empirical knowledge of the relative probability of conservation of various amino acids. Simulations are used to model and correct for errors in the estimates. The method was used to infer the amino acid composition of a large protein set in the Last Universal Ancestor (LUA) of all extant species. Relative to the modern protein set, LUA proteins were found to be generally richer in those amino acids that are believed to have been most abundant in the prebiotic environment and poorer in those amino acids that are believed to have been unavailable or scarce. It is proposed that the inferred amino acid composition of proteins in the LUA probably reflects historical events in the establishment of the genetic code.
Pigtailing the high-Q microsphere cavity:?a simple fiber coupler for optical whispering-gallery modes (1999)

We demonstrate a simple method for efficient coupling of standard single-mode optical fibers to a high- Q optical microsphere cavity. Phase-matched excitation of whispering-gallery modes is provided by an angle-polished fiber tip in which the core-guided wave undergoes total internal reflection. In the experimental setup, which included a microsphere with both an input and an output coupler, the total fiber-to-fiber transmission at resonance reached 23% (total insertion loss, 6.3 dB), with loaded quality factor Q> or =3 x 10(7) and unloaded Q approximately 1.2 x 10(8) at 1550 nm. A simple pigtailing method for microspheres permits their wider use in fiber optics and photonics devices.
Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein. (1993)

Although T cell responses to the quantitatively major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP), are likely to be of importance in the course of multiple sclerosis (MS), cell-mediated autoimmune responses to other myelin antigens, in particular quantitatively minor myelin antigens, such as myelin-associated glycoprotein (MAG) and the central nervous system-specific myelin oligodendrocyte glycoprotein (MOG), could also play a prevalent role in disease initiation or progression. Highly purified myelin antigens were used in this study to assess cell-mediated immune response to MOG in MS patients, in the context of the reactivity to other myelin antigens, MBP, PLP, and MAG. The greatest incidence of proliferative response by MS peripheral blood lymphocytes was to MOG, as 12 of 24 patients tested reacted and, of these, 8 reacted to MOG exclusively. In contrast, only 1 control individual of 16 tested reacted positively to MOG. The incidence of responses to MBP, PLP, and MAG did not differ greatly between MS patients and control individuals. A predominant T cell reactivity to MOG in MS suggests an important role for cell-mediated immune response to this antigen in the pathogenesis of MS.
New Advances in Interferon Therapy of Cancer (1997)

Substantial increases in both the understanding of the cellular mechanisms of actions of interferon (IFN) and in its clinical use in cancer have occurred in recent years. The efficacy of interferon for the treatment of select malignancies has been established, and IFN-&agr; and IFN-&bgr; have been approved by the Food and Drug Administration for multiple clinical indications. IFN-&agr; increased median survival and relapse-free survival in patients with locally advanced melanoma when used as adjuvant therapy and had modest activity against advanced disease. In other tumors where studies indicated that IFN lacked direct therapeutic activity, clinical trials suggested that it increased the antitumor activity of cytotoxic chemotherapeutic agents when used in combination therapy. IFN has substantial activity in chronic myelogenous leukemia, increasing survival in patients in early chronic phase when compared with conventional chemotherapy, and has some activity in non-Hodgkin's lymphoma in combination with cytotoxic agents. Recent molecular and pharmacologic studies defining cellular receptor activation, signal transduction pathways, and biochemical modulating activities of interferon have yet to be fully incorporated into clinical development. Further preclinical advances along with the expanding identification of potentially clinically sensitive tumors make it likely that the use of IFN in cancer chemotherapy will continue to grow.
The ETS Inhibitors YK-4-279 and TK-216 Are Novel Antilymphoma Agents (2019)

The ETS inhibitor YK-4-279 and its clinical derivative TK-216 represent a new class of agents with <i>in vitro</i> and <i>in vivo</i> antitumor activity in lymphomas. Although their detailed mechanism of action needs to be fully defined, in DLBCL they might act by targeting subtype-specific essential transcription factors.
Degrees of Freedom in Multiple-Antenna Channels: A Signal Space Approach (2005)

Multiple-antenna systems that are limited by the area and geometry of antenna arrays, are considered. Given these physical constraints, the limit on the available number of spatial degrees of freedom is derived. The commonly used statistical multiple-input multiple-output (MIMO) model is inadequate. Antenna theory is applied to take into account the area and geometry constraints, and to define the spatial signal space so as to interpret experimental channel measurements in an array-independent but manageable description of the physical environment. Based on these modeling strategies, for a spherical array of effective aperture A in a physical environment of angular spread |/spl Omega/| in solid angle, the number of spatial degrees of freedom is shown to be A|/spl Omega/| for uni-polarized antennas and 2A|/spl Omega/| for tri-polarized antennas. Together with the 2WT degrees of freedom for a system of bandwidth W transmitting in an interval T, the total degrees of freedom of a multiple-antenna channel is therefore 4WTA|/spl Omega/|.
Hepcidin antagonists for potential treatments of disorders with hepcidin excess (2014)

The discovery of hepcidin clarified the basic mechanism of the control of systemic iron homeostasis. Hepcidin is mainly produced by the liver as a propeptide and processed by furin into the mature active peptide. Hepcidin binds ferroportin, the only cellular iron exporter, causing the internalization and degradation of both. Thus hepcidin blocks iron export from the key cells for dietary iron absorption (enterocytes), recycling of hemoglobin iron (the macrophages) and the release of storage iron from hepatocytes, resulting in the reduction of systemic iron availability. The BMP/HJV/SMAD pathway is the major regulator of hepcidin expression that responds to iron status. Also inflammation stimulates hepcidin via the IL6/STAT3 pathway with a support of an active BMP/HJV/SMAD pathway. In some pathological conditions hepcidin level is inadequately elevated and reduces iron availability in the body, resulting in anemia. These conditions occur in the genetic iron refractory iron deficiency anemia and the common anemia of chronic disease (ACD) or anemia of inflammation. Currently, there is no definite treatment for ACD. Erythropoiesis-stimulating agents and intravenous iron have been proposed in some cases but they are scarcely effective and may have adverse effects. Alternative approaches aimed to a pharmacological control of hepcidin expression have been attempted, targeting different regulatory steps. They include hepcidin sequestering agents (antibodies, anticalins, and aptamers), inhibitors of BMP/SMAD or of IL6/STAT3 pathway or of hepcidin transduction (siRNA/shRNA) or ferroportin stabilizers. In this review we summarized the biochemical interactions of the proteins involved in the BMP/HJV/SMAD pathway and its natural inhibitors, the murine and rat models with high hepcidin levels currently available and finally the progresses in the development of hepcidin antagonists, with particular attention to the role of heparins and heparin sulfate proteoglycans in hepcidin expression and modulation of the BMP6/SMAD pathway.
Reduction in the size of features of patterned SAMs generated by microcontact printing with mechanical compression of the stamp (1995)

Sub‐micron size features can now be produced using the microcontact printing technique. The elastomeric stamp used to produce the features in self‐assembled monolayers (see figure) is mechanically compressed both one‐ and two‐dimensionally, resulting in a reduction of the size of the features by up to a factor of almost ten (e.g. 2.5 μm) while retaining the spatial regularities in the pattern. magnified image
The Escherichia coli aspartate receptor: sequence specificity of a transmembrane helix studied by hydrophobic-biased random mutagenesis (1999)

The Escherichia coli aspartate receptor is a dimer with two transmembrane sequences per monomer that connect a periplasmic ligand binding domain to a cytoplasmic signaling domain. The method of 'hydrophobic-biased' random mutagenesis, that we describe here, was used to construct mutant aspartate receptors in which either the entire transmembrane sequence or seven residues near the center of the transmembrane sequence were replaced with hydrophobic and polar random residues. Some of these receptors responded to aspartate in an in vivo chemotaxis assay, while others did not. The acceptable substitutions included hydrophobic to polar residues, small to larger residues, and large to smaller residues. However, one mutant receptor that had only a few hydrophobic substitutions did not respond to aspartate. These results add to our understanding of sequence specificity in the transmembrane regions of proteins with more than one transmembrane sequence. This work also demonstrates a method of constructing families of mutant proteins containing random residues with chosen characteristics.
Thrombospondin 3 (Thbs3), a new member of the thrombospondin gene family. (1992)

A third member of the thrombospondin gene family (Thbs3) has been partially characterized in the mouse. In both the mouse and humans, the Thbs3/THBS3 gene is located immediately upstream from the Muc1/MUC1 (episialin) gene; less than 3 kilobases separate the polyadenylation signal of one gene from the start of transcription of the other. The available coding sequence in Thbs3 shows a high degree of amino acid sequence identity to Thbs1 and Thbs2 (58 and 59%, respectively, in exons 15 and 16), but the exon/intron organization of Thbs3 appears to be more disparate than that of the two previously described members of the family. The shorter length of the Thbs3 mRNA (3.5 kilobases) can be attributed largely to a shorter 3'-untranslated region. The Thbs3 gene is expressed in a distinctive pattern in mouse tissues, with the highest level of expression in lung. This pattern suggests a unique function for the translation product of the Thbs3 gene.
Extracellular Heat Shock Proteins in Cell Signaling and Immunity (2007)

Extracellular stress proteins including heat shock proteins (Hsps) and glucose-regulated proteins (Grps) are emerging as important mediators of intercellular signaling and transport. Release of such proteins from cells is triggered by physical trauma and behavioral stress as well as exposure to immunological "danger signals." Stress protein release occurs both through physiological secretion mechanisms and during cell death by necrosis. After release into the extracellular fluid, Hsp or Grp may then bind to the surfaces of adjacent cells and initiate signal transduction cascades as well as the transport of cargo molecules, such as antigenic peptides. In addition, Hsp60 and Hsp70 are able to enter the bloodstream and may possess the ability to act at distant sites in the body. Many of the effects of extracellular stress proteins are mediated through cell-surface receptors. Such receptors include toll- like receptors (TLRs) 2 and 4, CD40, CD91, CCR5, and members of the scavenger receptor family, such as LOX-1 and SREC-1. The possession of a wide range of receptors for the Hsp and Grp family permits binding to a diverse range of cells and the performance of complex multicellular functions particularly in immune cells and neurons.
Cell proliferation in human arteriovenous fistulas used for hemodialysis. (1993)

The long-term patency of arteriovenous (AV) fistulas created for hemodialysis of renal-failure patients is usually measured in months, particularly when polytetrafluoroethylene (PTFE) material is interposed between the artery and vein. This is due to the rapid development of intimal hyperplastic lesions in the anastomosis region of the PTFE graft material with the vein. We studied the proliferative patterns in seven human AV fistulas removed at the time of fistula revision. Cell proliferation was determined by using an antibody to the proliferating cell nuclear antigen (PCNA), and specific cell types were identified by immunochemical reagents for smooth muscle cells, monocytes/macrophages, monocytes, lymphocytes, and endothelial cells. All venous segments exhibited a markedly hyperplastic intima. Vascularization of the intima and media by capillary-sized vessels was found. The main intimal cellular component was smooth muscle. Macrophages were usually seen around microvessels, and many also populated the perigraft region of the adventitia. In contrast to human atherosclerotic lesions, high rates of cell proliferation were observed in these fistulas. PCNA indices (percentage of cells that were PCNA positive [mean +/- SD]) were as follows: intima 17.7 +/- 11.3%, media 24 +/- 11.2%, and adventitia 20 +/- 11.6%. However, the distribution of PCNA-positive cells was not uniform. Instead, the PCNA index in microvessel-containing intimal fields was five to six times that of avascular fields (28.9 +/- 10.6% versus 4.9 +/- 4.5%, respectively, p < 0.001). Double immunolabeling revealed a large proportion of PCNA-positive microvascular endothelial cells and surrounding pericyte-like smooth muscle cells, as well as smooth muscle cells without visual connection to either microvessels or the lumen.(ABSTRACT TRUNCATED AT 250 WORDS)
Inverted Terminal Repeat Sequences Are Important for Intermolecular Recombination and Circularization of Adeno-Associated Virus Genomes (2004)

The relatively small package capacity (less than 5 kb) of adeno-associated virus (AAV) vectors has been effectively doubled with the development of dual-vector heterodimerization approaches. However, the efficiency of such dual-vector systems is limited not only by the extent to which intermolecular recombination occurs between two independent vector genomes, but also by the directional bias required for successful transgene reconstitution following concatemerization. In the present study, we sought to evaluate the mechanisms by which inverted terminal repeat (ITR) sequences mediate intermolecular recombination of AAV genomes, with the goal of engineering more efficient vectors for dual-vector trans-splicing approaches. To this end, we generated a novel AAV hybrid-ITR vector characterized by an AAV-2 and an AAV-5 ITR at opposite ends of the viral genome. This hybrid genome was efficiently packaged into either AAV-2 or AAV-5 capsids to generate infectious virions. Hybrid AV2:5 ITR viruses had a significantly lower capacity to form circular intermediates in infected cells than homologous AV2:2 and AV5:5 ITR vectors despite their similar capacity to express an encoded enhanced green fluorescent protein (EGFP) transgene. To examine whether the divergent ITR sequences contained within hybrid AV2:5 ITR vectors could direct intermolecular recombination in a tail-to-head fashion, we generated two hybrid ITR trans-splicing vectors (AV5:2LacZdonor and AV2:5LacZacceptor). Each delivered one exon of a beta-galactosidase minigene flanked by donor or acceptor splice sequences. These hybrid trans-splicing vectors were compared to homologous AV5:5 and AV2:2 trans-splicing vector sets for their ability to reconstitute beta-galactosidase gene expression. Results from this comparison demonstrated that hybrid ITR dual-vector sets had a significantly enhanced trans-splicing efficiency (6- to 10-fold, depending on the capsid serotype) compared to homologous ITR vectors. Molecular studies of viral genome structures suggest that hybrid ITR vectors provide more efficient directional recombination due to an increased abundance of linear-form genomes. These studies provide direct evidence for the importance of ITR sequences in directing intermolecular and intramolecular homologous recombination of AAV genomes. The use of hybrid ITR AAV vector genomes provides new strategies to manipulate viral genome conversion products and to direct intermolecular recombination events required for efficient dual-AAV vector reconstitution of the transgene.