gebhart/patrepeval huggingface dataset:
Implementation and performance of integrated application-controlled file caching, prefetching, and disk scheduling (1996)

As the performance gap between disks and micropocessors continues to increase, effective utilization of the file cache becomes increasingly immportant. Application-controlled file caching and prefetching can apply application-specific knowledge to improve file cache management. However, supporting application-controlled file caching and prefetching is nontrivial because caching and prefetching need to be integrated carefully, and the kernel needs to allocate cache blocks among processes appropriately. This article presents the design, implementation, and performance of a file system that integrates application-controlled caching, prefetching, and disk scheduling. We use a two-level cache management strategy. The kernel uses the LRU-SP (Least-Recently-Used with Swapping and Placeholders) policy to allocate blocks to processes, and each process integrates application-specific caching and prefetching based on the controlled-aggressive policy, an algorithm previously shown in a theoretical sense to be nearly optimal. Each process also improves its disk access latency by submittint its prefetches in batches so that the requests can be scheduled to optimize disk access performance. Our measurements show that this combination of techniques greatly improves the performance of the file system. We measured that the running time is reduced by 3% to 49% (average 26%) for single-process workloads and by 5% to 76% (average 32%) for multiprocess workloads.
Stability of crystalline proteins (2001)

By using two model proteins, glucose oxidase and lipase, we demonstrate that dry crystalline formulations are significantly more stable than their amorphous counterparts. The results of Fourier-transform infrared spectroscopy indicate that crystalline proteins better maintain their native conformation in accelerated stability studies. The lower tendency of crystalline proteins to aggregate is confirmed by size-exclusion chromatography. The data suggest that protein crystallization may significantly improve some aspects of protein handling, and change the way biopharmaceuticals are produced, formulated, and delivered.
Inhibiting glycosphingolipid synthesis ameliorates hepatic steatosis in obese mice # (2009)

These data indicate that inhibiting GSL synthesis ameliorates the liver pathology associated with obesity and diabetes, and may represent a novel strategy for treating fatty liver disease and NASH.
THE MOVEMENT OF CHLORIDE IONS IN THE CASE OF CONNECTING THE CONCRETE AND MORTAR THAT MIXED CHLORIDE IONS IMMOBILIZED MATERIAL (2014)

カルシウムアルミネート系の塩素固定化材を混和したモルタルと、内在塩分を多く含むコンクリートを打ち継いだ供試体を作製し、コンクリートからモルタルへの塩化物イオンの移動挙動について検討を行った。その結果、塩素固定化材を混和したモルタルは、打継ぎ界面付近のコンクリート側の塩化物イオン量を低減することが分かった。これは、コンクリートからモルタルへ浸透する可溶性塩化物イオンがモルタル内部でフリーデル氏塩として固定化され、打継ぎ界面付近の可溶性塩化物イオン量が低減するためと推察した。
Serum DNA can define tumor-specific genetic and epigenetic markers in gliomas of various grades (2010)

We evaluated whether cell-free circulating DNA can be used as a noninvasive approach for detection of genetic/epigenetic alterations in brain tumors during the course of the disease. Paired tumor-serum samples from 70 patients with either high-grade astrocytomas (n = 41) or oligodendrogliomas of various grades were analyzed. The median interval between surgery and serum sampling was 1 month (range 0.5-168 months). DNA was extracted from whole blood, serum, and paraffin-embedded tumor sections. Loss of heterozygosity (LOH) in chromosomes 1p, 19q, and 10q was assessed by polymerase chain reaction (PCR)-based microsatellite analysis. The methylation status of O(6)-methyl guanine methyltransferase (MGMT) and phosphatase and tensin homolog promoters was studied by methylation-specific PCR. LOH and/or methylation that could identify DNA as tumor-specific was found in 80.5% of astrocytic tumors and in all oligodendrogliomas. The rate of serum detection of these biomarkers was 51% and 55%, respectively, with specificity around 100%. The rate of serum detection did not differ between low- and high-grade oligodendrogliomas. Statistically significant tumor-serum concordance was found for MGMT methylation in both astrocytic tumors (83%; P < .001) and oligodendroglial tumors (72%; P < .003) and for LOH of 10q (79%; P < .002) and 1p (62%; P < .03) in oligodendrogliomas. We conclude that serum DNA in glial tumors is informative for both LOH and aberrant gene promoter methylation analysis during the course of the disease. The sensitivity is moderate and specificity is high for both low- and high-grade tumors. Future studies should identify a panel of biomarkers that bear the highest potential for clinical application.
CRISPR/Cas9 editing of APP C-terminus attenuates β-cleavage and promotes α-cleavage (2018)

CRISPR/Cas9 guided gene-editing is a potential therapeutic tool, however application to neurodegenerative disease models has been limited. Moreover, conventional mutation correction by gene-editing would only be relevant for the small fraction of neurodegenerative cases that are inherited. Here we introduce a CRISPR/Cas9-based strategy in cell and animal models to edit endogenous amyloid precursor protein (APP) at the extreme C-terminus and reciprocally manipulate the amyloid pathway, attenuating APP-β-cleavage and Aβ production, while up-regulating neuroprotective APP-α-cleavage. APP N-terminus and compensatory APP-homologues remain intact, with no apparent effects on neurophysiology in vitro. Robust APP-editing is seen in human iPSC-derived neurons and mouse brains with no detectable off-target effects. Our strategy likely works by limiting APP and BACE-1 approximation, and we also delineate mechanistic events that abrogates APP/BACE-1 convergence in this setting. Our work offers conceptual proof for a selective APP silencing strategy.
The Cu Communicator System (1999)

The CU Communicator system is our initial testbed for research leading to advanced dialog systems enabling robust and graceful human computer interaction. It is a DARPA hub compliant system for the DARPA Communicator task, and was demonstrated at the DARPA workshop in June 1999. Robustness and portability of spoken dialog systems are two of the issues we attempt to address in the project. We use robust parsing and dialog control strategies to be as flexible as possible to user variance. In order to make the systems easier to develop, we have adopted a largely declarative representation where the bulk of the domain specific information is provided in external files. 1. INTRODUCTION In April 1999, the University of Colorado speech group began development of the CU Communicator system, a Hubcompliant implementation of the DARPA Communicator task[1][2].The system combines continuous speech recognition, natural language understanding and flexible dialog control to enable natural conversat...
Photoacoustic generation: all-optical fibre transducers (2002)

Innovative photoacoustic transducers for ultrasonic NDE, smart structure, and clinical diagnosis are proposed. The working principle is based on thermal conversion of laser pulses into a metallic film evaporated directly onto the tip of an optical fibre, or, alternatively, on the extrados of an uncladded and U-bent fibre. Unique features of the proposed transducers are: very high miniaturization and potential easy embedding in smart structure. Additional advantages are: good conversion efficiency, high acoustic power in high frequency range, large bandwidth, and spectral purity of the ultrasonic signal.
Function of GB1 and GB2 subunits in G protein coupling of GABA B receptors (2001)

Many G protein-coupled receptors (GPCRs) have recently been shown to dimerize, and it was suggested that dimerization may be a prerequisite for G protein coupling. γ-aminobutyric acid type B (GABA B ) receptors (GPCRs for GABA, a major inhibitory neurotransmitter in the brain) are obligate heterodimers of homologous GB1 and GB2 subunits, neither of which is functional on its own. This feature of GABA B receptors allowed us to examine which of the eight intracellular segments of the heterodimeric receptor were important for G protein activation. Replacing any of the three intracellular loops of GB2 with their GB1 counterparts resulted in nonfunctional receptors. The deletion of the complete GB2 C terminus significantly attenuated the receptor function; however, the proximal 36 residues were sufficient for reconstitution of wild type-like receptor activity. In contrast, the GB1 C terminus could be deleted and GB1 intracellular loops replaced with their GB2 or mGluR1 equivalents without affecting the receptor function. In addition, a large portion of the GB1 i2 loop could be replaced with a random coil peptide without any functional consequences. Thus, GB2 intracellular segments are solely responsible for specific coupling of GABA B receptors to their physiologic effectors, G i and G protein-activated K + channels. These findings strongly support a model in which a single GPCR monomer is sufficient for all of the specific G protein contacts.
Oxygen Radical Production by Alveolar Inflammatory Cells in Idiopathic Pulmonary Fibrosis (1990)

Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung disease characterized by the accumulation of alveolar macrophages (AMs) and neutrophils in the lower respiratory tract, parenchymal cell injury, and fibrosis of the alveolar structure. Reactive oxygen intermediates (ROI) are claimed to be a major cause of tissue damage in IPF; however, the source of ROI has not been unequivocally identified. AMs, as well as neutrophils, are capable of releasing these agents. The contributions of these possible sources are not known. To address this question, we evaluated the spontaneous and stimulated (PMA or zymosan) ROI release of total bronchoalveolar cells and isolated AMs in 14 patients with IPF by means of luminol-enhanced chemiluminescence. Bronchoalveolar lavage (BAL) cells from 17 individuals without any signs of inflammation served as controls. In comparison with the controls, the spontaneous as well as the stimulated ROI release of total BAL cells in IPF are markedly increased (20,763.9 +/- 5,079.3 versus 2,509.5 +/- 300.6 counts/10 s/2.10(5) cells, spontaneously, IPF versus control; 106,819.3 +/- 33,802.8 versus 8,919 +/- 1,357.9 PMA induced; 41,597.1 +/- 8,442.6 versus 6,223.8 +/- 1,025.1 zymosan induced, p less than 0.001). Measurement of the ROI release of purified AMs revealed that these cells produce the bulk part of ROI released by BAL cells (84%). In spite of the fact that, on a per cell basis, the ROI release of neutrophils is 1.7-fold of that of AMs, there is no correlation between the ROI production of total BAL cells and the percentage of neutrophils in BAL, demonstrating a minor role of these cells in the generation of the total ROI burden in IPF.(ABSTRACT TRUNCATED AT 250 WORDS)
Partial Purification and Characterization of Two <i>Cladosporium herbarum </i>Allergens (1979)

Two important Cladosporium herbarum allergens (Ag-54 and Ag-32) were partly purified by means of diafiltration, gel filtration and isoelectric focusing. Modifications of quantitative immunological techniques, including autoradiography, were used as assay systems for allergenic activity and to provide a basis for evaluation of the immunological purity of the allergens. Ag-54 appeared to have a molecular weight of approximately 25,000 daltons and an isoelectric point of 5.0. The molecular weight of Ag-32 appeared to be approximately 13,000 daltons. It consisted of 5 molecular species differing in isoelectric points from 3.4 to 4.4 in intervals of approximately 0.25 pH units. These variants of Ag-32 seemed to be antigenically and allergenically identical.
Conjugated Polymer Sensors: Design Principles Towards Enhanced Versatility (2004)

A description of how semiconducting fluorescent polymers function as chemosensors for a variety of chemical vapors is presented. Amplification is achieved by transport of optically induced excitations throughout a polymer film. Careful and thoughtful design of polymer chemical structures is crucial to achieving high sensitivity towards nitroaromatic explosives such as trinitrotoluene (TNT) and dinitrotoluene (DNT). These semiconductive materials have been incorporated into functional sensory devices used for ultratrace explosive detection in the search for hidden landmines. Research efforts in our group have been aimed improving the sensitivity, selectivity, and versatility of conjugated polymer sensors through rational molecularly design.
Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy (2001)

In human breast carcinomas, overexpression of the macrophage colony-stimulating factor (CSF-1) and its receptor (CSF-1R) correlates with poor prognosis. To establish if there is a causal relationship between CSF-1 and breast cancer progression, we crossed a transgenic mouse susceptible to mammary cancer with mice containing a recessive null mutation in the CSF-1 gene (Csf1(op)) and followed tumor progression in wild-type and null mutant mice. The absence of CSF-1 affects neither the incidence nor the growth of the primary tumors but delayed their development to invasive, metastatic carcinomas. Transgenic expression of CSF-1 in the mammary epithelium of both Csf1(op)/Csf1(op) and wild-type tumor-prone mice led to an acceleration to the late stages of carcinoma and to a significant increase in pulmonary metastasis. This was associated with an enhanced infiltration of macrophages into the primary tumor. These studies demonstrate that the growth of mammary tumors and the development to malignancy are separate processes and that CSF-1 selectively promotes the latter process. CSF-1 may promote metastatic potential by regulating the infiltration and function of tumor-associated macrophages as, at the tumor site, CSF-1R expression was restricted to macrophages. Our data suggest that agents directed at CSF-1/CSF-1R activity could have important therapeutic effects.
High-efficiency identification of genes by functional analysis from a retroviral cDNA expression library (1994)

Retroviral gene transfer efficiently delivers genes of interest stably into target cells, and expression cDNA cloning has been shown to be highly successful. Considering these two advantages, we now report a method by which one can identify genes stimulating cell growth through functional analysis. The first step requires the construction of a retroviral cDNA expression library and the optimization of transfection of vector DNA into virus packaging cells. The second step involves the cocultivation of target cells with libraries of retrovirus-producing cells, resulting in the amplification of target cells transduced with a gene(s) stimulating cell growth. Under standardized conditions of transfection, we detected an average of 4,000 independent clones per dish, among which expression of a retroviral beta-galactosidase gene at an abundance of 0.2% could be detected. Next, we demonstrated the augmentation of the sensitivity of the assay by retroviral infection and functional analysis. We did this by cocultivating factor-dependent (FD) cells with dishes of GP/E cells transfected with plasmids containing various molar ratios of pN2-IL3 DNA and retroviral library cDNA and by determining the highest dilution of pN2-IL3 which still resulted in the conversion of FD cells to factor independence. The retroviral interleukin-3 gene at an abundance as low as 0.001% could be detected. Indeed, we were able to detect from FD cells the development of factor-independent colonies with different phenotypes after retroviral transfer of cDNAs from an immortalized hemopoietic stem cell line. Thus, the combination of a standardized high-efficiency DNA transfection and retrovirus-mediated gene transfer should facilitate the identification of genes capable of conferring to target FD cells a detectable new function or phenotype. By scaling up the size of the experiment realistically during screening, the assay can detect cDNA at an abundance of lower than 0.0001%.
Analyzing Customer Journey with Process Mining: From Discovery to Recommendations (2018)

Customer journey analysis is a hot topic in marketing. Understanding how the customers behave is crucial and is considered as one of the key drivers of business success. To the best of our knowledge, a data-driven approach to analyze the customer journey is still missing. For instance, web analytics tools like Google Analytics provide an oversimplified version of the user behavior, focusing more on the frequency of page visits rather than discovering the process of the visit itself. On the other hand, customer journey maps have shown their usefulness, but they need to be created manually by domain experts. This paper contributes a novel approach for applying process mining techniques to web log customer journey analysis. Through process mining we are able to (i) discover the process that better describes the user behavior, (ii) find useful insights, (iii) compare the processes of different clusters of users, and then (iv) use this analysis to improve the journey by optimizing some KPIs (Key Performance Indicators) via personalized recommendations based on the user behavior. We show through a real-life case study a proof of the correctness of the introduced concept by improving the recommender accuracy when incorporating additional context information about the journey as extracted from the process model.
Minimal haplotype tagging (2003)

The high frequency of single-nucleotide polymorphisms (SNPs) in the human genome presents an unparalleled opportunity to track down the genetic basis of common diseases. At the same time, the sheer number of SNPs also makes unfeasible genome-wide disease association studies. The haplotypic nature of the human genome, however, lends itself to the selection of a parsimonious set of SNPs, called haplotype tagging SNPs (htSNPs), able to distinguish the haplotypic variations in a population. Current approaches rely on statistical analysis of transmission rates to identify htSNPs. In contrast to these approximate methods, this contribution describes an exact, analytical, and lossless method, called BEST (Best Enumeration of SNP Tags), able to identify the minimum set of SNPs tagging an arbitrary set of haplotypes from either pedigree or independent samples. Our results confirm that a small proportion of SNPs is sufficient to capture the haplotypic variations in a population and that this proportion decreases exponentially as the haplotype length increases. We used BEST to tag the haplotypes of 105 genes in an African-American and a European-American sample. An interesting finding of this analysis is that the vast majority (95%) of the htSNPs in the European-American sample is a subset of the htSNPs of the African-American sample. This result seems to provide further evidence that a severe bottleneck occurred during the founding of Europe and the conjectured "Out of Africa" event.
Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses (2019)

Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, suggesting that exogenous DCs stimulate antitumor immunity by transferring antigens (Ags) to endogenous DCs. Such Ag transfer functions are most commonly ascribed to monocytes, implying that undifferentiated monocytes would function equally well as a vaccine modality and need not be differentiated to DCs to be effective. Here, we used several murine cancer models to test the antitumor efficacy of undifferentiated monocytes loaded with protein or peptide Ag. Intravenously injected monocytes displayed antitumor activity superior to DC vaccines in several cancer models, including aggressive intracranial glioblastoma. Ag-loaded monocytes induced robust CTL responses via Ag transfer to splenic CD8+ DCs in a manner independent of monocyte APC activity. Ag transfer required cell-cell contact and the formation of connexin 43-containing gap junctions between monocytes and DCs. These findings demonstrate the existence of an efficient gap junction-mediated Ag transfer pathway between monocytes and CD8+ DCs and suggest that administration of tumor Ag-loaded undifferentiated monocytes may serve as a simple and efficacious immunotherapy for the treatment of human cancers.
The role of CD45 and CD45‐associated molecules in T cell activation (1997)

CD45 (lymphocyte common antigen) is a receptor-linked protein tyrosine phosphatase that is expressed on all leucocytes, and which plays a crucial role in the function of these cells. On T cells the extracellular domain of CD45 is expressed in several different isoforms, and the particular isoform(s) expressed depends on the particular subpopulation of cell, their state of maturation, and whether or not they have previously been exposed to antigen. It has been established that the expression of CD45 is essential for the activation of T cells via the TCR, and that different CD45 isoforms display a different ability to support T cell activation. Although the tyrosine phosphatase activity of the intracellular region of CD45 has been shown to be crucial for supporting signal transduction from the TCR, the nature of the ligands for the different isoforms of CD45 have been elusive. Moreover, the precise mechanism by which potential ligands may regulate CD45 function is unclear. Interestingly, in T cells CD45 has been shown to associate with numerous molecules, both membrane associated and intracellular; these include components of the TCR-CD3 complex and CD4/CD8. In addition, CD45 is reported to associate with several intracellular protein tyrosine kinases including p56lck and p59fyn of the src family, and ZAP-70 of the Syk family, and with numerous proteins of 29-34 kDa. These CD45-associated molecules may play an important role in regulating CD45 tyrosine phosphatase activity and function. However, although the role of some of the CD45-associated molecules (e.g. CD45-AP and LPAP) has become better understood in recent years, the role of others still remains obscure. This review aims to summarize recent findings on the role of CD45 and CD45-associated molecules in T cell activation, and to highlight issues that seem relevant to ongoing research in this area.
α2A‐Adrenoceptor antagonism increases insulin secretion and synergistically augments the insulinotropic effect of glibenclamide in mice (2008)

These results suggest that (+/-)-efaroxan and phentolamine increase insulin secretion by inhibition of beta-cell alpha2A-adrenoceptors, and demonstrate a critical role for alpha2A-adrenoceptors in limiting sulphonylurea-induced hyperinsulinaemia and hypoglycaemia.
A DOUBLE BLIND CROSSOVER TRAIALOF LOW LEVEL LASER THERAPY IN THE TREATMENT OF POST HERPETIC NEURALGIA (1989)

Post herpetic neuralgia can be an extremely painful condition which in many cases proves resistant to all the accepted forms of treatment. It is frequently most severe in the elderly and may persist for years with no predictable course. This trial was designed as - double blind assessment of the efficacy of low level laser therapy in the relief of the pain of post herpetic neuralgia with patients acting as their own controls. Admission to the trial was limited to patients with established post herpetic neuralgia of at least six months duration and who had shown little or no response to conventional methods of treatment. Measurements of pain intensity and distribution were noted over a period of eight treatments in two groups of patients each of which received four consecutive laser treatments. The results demonstrate a significant reduction in both pain intensity and distribution following a course of low level laser therapy.