gebhart/patrepeval huggingface dataset:
Using probabilistic reasoning to automate software tuning (2004)

Manually tuning the parameters or "knobs" of a complex software system is an extremely difficult task. Ideally, the process of software tuning should be automated, allowing software systems to reconfigure themselves as needed in response to changing conditions. We present a methodology that uses a probabilistic, graphical model known as an influence diagram as the foundation of an effective, automated approach to software tuning. We have used our methodology to simultaneously tune four knobs from the Berkeley DB embedded database system, and our results show that an influence diagram can effectively generalize from training data for this domain.
Lyn-Deficient Mice Develop Severe, Persistent Asthma: Lyn Is a Critical Negative Regulator of Th2 Immunity (2005)

The etiology of asthma, a chronic inflammatory disorder of the airways, remains obscure, although T cells appear to be central disease mediators. Lyn tyrosine kinase has been implicated as both a facilitator and inhibitor of signaling pathways that play a role in allergic inflammation, although its role in asthma is unclear because Lyn is not expressed in T cells. We show in the present study that Lyn-/- mice develop a severe, persistent inflammatory asthma-like syndrome with lung eosinophilia, mast cell hyperdegranulation, intensified bronchospasm, hyper IgE, and Th2-polarizing dendritic cells. Dendritic cells from Lyn-/- mice have a more immature phenotype, exhibit defective inhibitory signaling pathways, produce less IL-12, and can transfer disease when adoptively transferred into wild-type recipients. Our results show that Lyn regulates the intensity and duration of multiple asthmatic traits and indicate that Lyn is an important negative regulator of Th2 immune responses.
Prevalence of Platelet Nonresponsiveness to Aspirin in Patients Treated for Secondary Stroke Prophylaxis and in Patients With Recurrent Ischemic Events (2008)

To determine the prevalence of platelet nonresponsiveness to aspirin treatment for secondary stroke prophylaxis, the authors studied consecutive patients during a 29-month period. Information regarding their ischemic events, risk factors, and medications was collected. Platelet aggregation in response to collagen and arachidonic acid was used to determine platelet responsiveness to aspirin. A total of 653 patients were evaluated. Of these, 129 patients (20%) were determined to be nonresponsive to aspirin based on continued platelet aggregation in response to collagen, arachidonic acid, or both. A total of 87 (13%) of the 653 patients were clinical aspirin failures (ie, presented with new focal cerebral ischemic symptoms while taking aspirin). Of the patients with new cerebral ischemic symptoms, 57 (66%) were determined to be platelet nonresponsive to aspirin. The odds ratio for platelet nonresponsiveness to aspirin in patients who suffered a recurrent ischemic event while taking aspirin was 14.25 (95% confidence interval: 8.5-23.7; P < .5). Continued platelet aggregation despite aspirin treatment occurred in 20% of ambulatory patients treated for secondary stroke prophylaxis. The prevalence of nonresponsiveness to aspirin was statistically higher in those patients who suffered recurrent cerebral ischemia while taking aspirin (P < .5) compared with patients who remained without new ischemic symptoms.
Design, Synthesis and Biological Evaluation of a Library of Thiocarbazates and Their Activity as Cysteine Protease Inhibitors (2010)

Recently, we identified a novel class of potent cathepsin L inhibitors, characterized by a thiocarbazate warhead. Given the potential of these compounds to inhibit other cysteine proteases, we designed and synthesized a library of thiocarbazates containing diversity elements at three positions. Biological characterization of this library for activity against a panel of proteases indicated a significant preference for members of the papain family of cysteine proteases over serine, metallo-, and certain classes of cysteine proteases, such as caspases. Several potent inhibitors of cathepsin L and S were identified. The SAR data were employed in docking studies in an effort to understand the structural elements required for cathepsin S inhibition. This study provides the basis for the design of highly potent and selective inhibitors of the papain family of cysteine proteases.
Pilot-scale production of murine monoclonal antibodies in agitated, ceramic-matrix or hollow-fiber cell culture systems. (1993)

The purpose of this research was to compare three bioreactor systems for the pilot-scale production of monoclonal antibodies (MAbs). We needed to produce gram quantities of murine MAbs against human prostatic acid phosphatase for use in fragmentation, radiolabeling and in vivo radio-imaging studies. The stable hybridoma cell line secreting IgG1 antibodies was chosen for production. Of the available bioreactor systems, we chose to test an agitating 30-liter bioreactor in repeated batch mode, a ceramic-matrix bioreactor in both repeated batch and continuous perfusion modes and a hollow-fiber bioreactor in continuous perfusion mode. The highest cultured MAb yield, 151 +/- 126 mg/day (mean +/- SD, n = 22), was achieved in the 30-liter bioreactor in repeated batch mode with the MAb being harvested in a large volume of medium, giving a reactor productivity of 4.3 +/ 3.4 mg/liter/day (mean +/- SD, n = 22). The most concentrated MAb was harvested from the continuously perfused hollow-fiber bioreactor, which had the highest reactor productivity, 307 +/ 142 mg/liter/day (mean +/- SD, n = 47) and an average rate of MAb production of 55.3 +/- 25.7 mg/day (mean +/- SD, n = 47). Taking the use of serum into consideration, the cost of MAb production was lowest in the continuously fed and harvested ceramic-matrix and hollow-fiber cell culture systems. A compact blood glucose meter proved to be a novel and suitable device for the rapid monitoring of glucose concentrations in hybridoma cultures.
The Effect of Human β2-Microglobulin on Major Histocompatibility Complex I Peptide Loading and the Engineering of a High Affinity Variant (1998)

The ability to directly load cell surface major histocompatibility complex (MHC) class I molecules with peptides provides a potentially powerful approach toward the development of vaccines to generate cell-mediated immunity. We demonstrate that exogenous beta2-microglobulin (beta2m) stabilizes human cell surface MHC I molecules and facilitates their loading with exogenous peptides. Additionally, using three-dimensional crystal structures and known interaction sites between MHC I heavy chains and beta2m, we engineered variants of human beta2m (hbeta2m) with a single serine substitution at residue 55. This alteration was predicted to promote hydrophobic interactions at the MHC I heavy chain/beta2m interface and displace an ordered water molecule. Compared with hbeta2m, the serine to valine substitution at residue 55 had improved ability to bind to cell surface HLA-A1, HLA-A2, and HLA-A3 molecules, facilitate exogenous peptide loading, and promote recognition by peptide-specific T cells. The inclusion of hbeta2m or higher affinity variants when pulsing cells with MHC-restricted peptides increases the efficiency of peptide loading 50-80-fold. Therefore, the inclusion of hbeta2m in peptide-based vaccines may increase cell surface antigen densities above thresholds that allow recognition of peptide antigens by the immune system, particularly for cryptic, subdominant, or marginally antigenic peptides.
Active Scheme to Measure Throughput of Wireless Access Link in Hybrid Wired-Wireless Network (2012)

In this letter, we propose an active scheme to measure the download throughput of an IEEE 802.11 wireless access link in a hybrid wired-wireless network. The proposed scheme is based on sending pairs of probing packets to a wireless end host to determine the smallest and average intra-packet gaps of the probing packets that are used for the estimation of the constant dispersion gap that wireless access creates. We present experimental evaluations of the proposed scheme, and the obtained results show that the proposed scheme achieves high measurement accuracy. Furthermore, we show that the proposed scheme is able to work under the presence of cross traffic along the path.
Effects of fibril- or fixed-collagen on matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1 production in the human hepatocyte cell line HLE (2005)

These results indicated that, in HLE cells, fibril- and fixed-collagen have opposite effects on MMP-1 production without affecting TIMP production. Fibril collagen induced collagenase activity by up-regulation of MMP-1 production without affecting TIMP-1 production. By contrast, fixed collagen reduced MMP-1 production. Our results suggest that hepatocytes might also play an important role in the regulation of the hepatic fibrosis alongside HSC.
Identification of sequences responsible for acute-phase induction of human C-reactive protein (1988)

Human C-Reactive protein (CRP) is inducible in liver cells during acute inflammation. Around 90 bp from the 5' flanking region of the human CRP gene contain, as shown here, information to induce the expression of a linked bacterial CAT gene specifically in human hepatoma (Hep3B) cells. The promoter is induced rapidly, faithfully and at high efficiency when transfected cells are exposed to conditioned medium from lipopolysaccharide stimulated peripheral monocytes. The sequences required for inducibility are located immediately upstream to the TATA element. A DNA segment from base -121 to -50 is capable of inducing transcription from the heterologous SV40 early promoter. Induction of CRP expression is probably exerted via the binding of at least one positive trans-acting factor.
An Anti-IL-12p40 Antibody Down-Regulates Type 1 Cytokines, Chemokines, and IL-12/IL-23 in Psoriasis (2006)

Psoriasis is characterized by activation of T cells with a type 1 cytokine profile. IL-12 and IL-23 produced by APCs are essential for inducing Th1 effector cells. Promising clinical results of administration of an Ab specific for the p40 subunit of IL-12 and IL-23 (anti-IL-12p40) have been reported recently. This study evaluated histological changes and mRNA expression of relevant cytokines and chemokines in psoriatic skin lesions following a single administration of anti-IL-12p40, using immunohistochemistry and real-time RT-PCR. Expression levels of type 1 cytokine (IFN-gamma) and chemokines (IL-8, IFN-gamma-inducible protein-10, and MCP-1) were significantly reduced at 2 wk posttreatment. The rapid decrease of these expression levels preceded clinical response and histologic changes. Interestingly, the level of an anti-inflammatory cytokine, IL-10, was also significantly reduced. Significant reductions in TNF-alpha levels and infiltrating T cells were observed in high responders (improvement in clinical score, > or =75% at 16 wk), but not in low responders. Of importance, the levels of APC cytokines, IL-12p40 and IL-23p19, were significantly decreased in both responder populations, with larger decreases in high responders. In addition, baseline levels of TNF-alpha significantly correlated with the clinical improvement at 16 wk, suggesting that these levels may predict therapeutic responsiveness to anti-IL-12p40. Thus, in a human Th1-mediated disease, blockade of APC cytokines by anti-IL-12p40 down-regulates expression of type 1 cytokines and chemokines that are downstream of IL-12/IL-23, and also IL-12/IL-23 themselves, with a pattern indicative of coordinated deactivation of APCs and Th1 cells.
Vascular permeability factor (vascular endothelial growth factor) in guinea pig and human tumor and inflammatory effusions. (1993)

Vascular permeability factor (VPF), also known as vascular endothelial growth factor, is a dimeric M(r) 34,000-42,000 glycoprotein that possesses potent vascular permeability-enhancing and endothelial cell-specific mitogenic activities. It is synthesized by many rodent and human tumor cells and also by some normal cells. Recently we developed a sensitive and specific time-resolved immunofluorometric assay for quantifying VPF in biological fluids. We here report findings with this assay in guinea pigs and patients with both malignant and nonmalignant effusions. Line 1 and line 10 tumor cells were injected into the peritoneal cavities of syngeneic strain 2 guinea pigs, and ascitic fluid, plasma, and urine were collected at various intervals. Within 2 to 4 days, we observed a time-dependent, parallel increase in VPF, ascitic fluid volume, and tumor cell numbers in animals bearing either tumor line; in contrast, VPF was not detected in plasma or urine, even in animals with extensive tumor burdens. However, low levels of VPF were detected in the inflammatory ascites induced by i.p. oil injection. In human studies, high levels of VPF (> 10 pM) were measured in 21 of 32 effusions with cytology-documented malignant cells and in only seven of 35 effusions without cytological evidence of malignancy. Thus, VPF levels in human effusions provided a diagnostic test for malignancy with a sensitivity of 66% and a specificity of 80% (perhaps as high as 97% in that six of the seven cytology-negative patients with VPF levels > 10 pM had cancer as determined by other criteria). As in the animal tumor models, VPF was not detected in serum or urine obtained from patients with or without malignant ascites. Many nonmalignant effusions contained measurable VPF but, on average, in significantly smaller amounts than were found in malignant effusions. VPF levels in such fluids correlated strongly (p = 0.59, P < 0.001) with monocyte and macrophage content. Taken together, these data relate ascitic fluid accumulation to VPF concentration in a well-defined animal tumor system and demonstrate, for the first time, the presence of VPF in human malignant effusions. It is likely that VPF expression by tumor and mononuclear cells contributes to the plasma exudation and fluid accumulation associated with malignant and certain inflammatory effusions. The VPF assay may prove useful for cancer diagnosis as a supplement to cytology, especially in tumors that grow in the pleural lining but not as a suspension in the effusions that they induce.
Curcumin Inhibits Constitutive STAT3 Phosphorylation in Human Pancreatic Cancer Cell lines and Downregulation of Survivin/BIRC5 Gene Expression (2009)

The purpose of this study was to determine the effect of curcumin on Survivin/BIRC5 and on the role of signal transducer and activator of transcription 3 (STAT3) activation in Survivin/ BIRC5. We incubated two pancreatic cancer cell lines with different amounts of curcumin. This resulted in a downregulation of proliferation in all cell lines tested. The expression of Survivin/BIRC5 on mRNA and protein level was significantly downregulated and the phosphorylation of STAT3 was blocked. Treatment of pancreatic cancer cells with curcumin resulted in an induction of apoptosis. The results indicate that curcumin inhibits several key factors in cancer cellular pathways and may be of interest in pancreatic cancer.
The Modern Network Theory Approach to Microwave Filter Design (1968)

A review of the modern network theory approach to microwave filter design based on Richards' transformation is given. Basic concepts are discussed, including the use of Kuroda's identities and the specialized theory of optimum filter forms. Applications of the theory presented to elliptic-function filters, special rejectiontype filters, and multiplexers are given. Throughout the presentation, emphasis is placed on basic methods and techniques rather than on detailed design procedures.
Semaphorins and their receptors in olfactory axon guidance. (1999)

The mammalian olfactory system is capable of discriminating among a large variety of odor molecules and is therefore essential for the identification of food, enemies and mating partners. The assembly and maintenance of olfactory connectivity have been shown to depend on the combinatorial actions of a variety of molecular signals, including extracellular matrix, cell adhesion and odorant receptor molecules. Recent studies have identified semaphorins and their receptors as putative molecular cues involved in olfactory pathfinding, plasticity and regeneration. The semaphorins comprise a large family of secreted and transmembrane axon guidance proteins, being either repulsive or attractive in nature. Neuropilins were shown to serve as receptors for secreted class 3 semaphorins, whereas members of the plexin family are receptors for class 1 and V (viral) semaphorins. The present review will discuss a role for semaphorins and their receptors in the establishment and maintenance of olfactory connectivity.
Phosphorus removal from wastewater using an algal turf scrubber (1996)

Algal turf scrubbing is a novel technology for the treatment of agricultural runoff and eutrophic lake water and may have application for wastewater treatment. The algal turf scrubber (ATS)TM consists of a natural, mixed assemblage of attached periphyton, microalgae and bacteria which colonise an inclined floway over which wastewater flows in a series of pulses. A large-scale ATS (152.4 m long 6.5 m wide) was constructed in Patterson, California and tested in conjunction with UV disinfection over one year for its ability to treat secondary effluent from an evaporation pond. The hydraulic loading rate of the wastewater was varied between 436 and 1226 m3 per day and various operational parameters were tested. The biomass was mechanically harvested from the floway at one or two week intervals depending upon the season. This paper will present the results for phosphorus removal and productivity of the algal turf. Phosphorus removal from the secondary wastewater was measured twice a week during four, 8 week quarters corresponding to the solar seasons. The phosphorus content of the harvested solids was also measured during these periods. Based on the mean percentage of P (2.1 %) in the harvested solids and the mean productivity (35 g m−2 d−1), the yearly mean removal of phosphorus was 0.73 ± 0.28 g m−2 d−1. An inverse relationship was found between reduction in hydraulic loading rate and increase in pH, phosphorus removal and hardness reduction by the ATS. This indicated that pH mediated precipitation probably accounts for much of the phosphorus removal by the ATS and for the high mean phosphorus content of the harvested solids. Measurement of nutrient concentrations in influent and effluent of the ATS over 24 hours showed that at night phosphorus removal declined. These results indicate the potential of the ATS for phosphorus removal from wastewaters and suggest that removal may be easily controlled by altering the hydraulic loading rate.
Minimal determinant expressed by a recombinant vaccinia virus elicits therapeutic antitumor cytolytic T lymphocyte responses. (1995)

Anticancer vaccine strategies can now target intracellular antigens that are involved in the process of malignant transformation, such as oncogene products or mutated tumor suppressor genes. Fragments of these antigens, generally 8-10 amino acids in length and complexed with MHC class I molecules, can be recognized by CD8+ T lymphocytes (TCD8+). To explore the possibility of using a genetically encoded, minimally sized fragment of an intracellular antigen as an immunogen, we constructed a recombinant vaccinia virus encoding an 8-residue peptide derived from chicken ovalbumin that is known to associate with the mouse H-2Kb molecule. Compared to standard methods of immunization, recombinant molecule. Compared to standard methods of immunization, recombinant vaccinia virus expressing the minimal determinant as well as full length ovalbumin were the only approaches that elicited specific primary lytic responses in C57BL/6 mice against E.G7OVA, a transfectant of the murine thymoma EL4 containing the ovalbumin gene. Stimulating these effectors in vitro with OVA257-264 peptide induced H-2Kb-restricted TCD8+ that not only lysed but also specifically secreted IFN-gamma in response to an antigen. Furthermore, when transferred adoptively, these anti-OVA257-264 TCD8+ cells significantly reduced the growth of established ovalbumin-transfected tumors in a pulmonary metastasis model system. Synthetic transfected tumors in a pulmonary metastasis model system. Synthetic oligonucleotides encoding minimal antigenic determinants within expression constructs may be a useful approach for treatment of neoplastic disease, thus avoiding the potential hazards of immunizing with full-length cDNAs that are potentially oncogenic.
Conversion of Biorenewable Feedstocks: New Challenges in Heterogeneous Catalysis (2010)

For biorenewable feedstocks to serve as a significant source of chemicals and/or fuels, the development of new chemical processes as well as biological processes will be required. However, the conversion of biorenewable feedstocks with heterogeneous catalyst-based processes provides new challenges in inorganic catalyst research and development relative to historical work with petrochemical feedstocks. These catalyst and process challenges include the need to convert highly functionalized molecules with high selectivity, to develop stable catalytic liquid−solid interfaces in which the liquid phase is commonly aqueous, to control solvent phase effects and to develop novel reaction systems. While some of these challenges will be addressed using novel catalytic materials, others will need to be overcome through design of new catalytic reaction systems. Examples of emerging research results demonstrating unique approaches that have been taken to begin to address the efficient conversion of biorenewable feedstocks to chemicals and fuels are discussed.
C‐terminal lysine processing of human immunoglobulin G2 heavy chain in vivo (2010)

Although human IgG heavy chain genes encode a C-terminal lysine, this residue is mostly absent from the endogenous antibodies isolated from serum. Some low but variable level of C-terminal lysine is present on therapeutic antibodies expressed in mammalian cell culture systems. Here, we monitored the C-terminal lysine processing of a recombinant human IgG2 antibody after intravenous injection into human subjects. Peptide mapping of the therapeutic antibody isolated from serum samples by affinity purification was used to quantify the C-terminal lysine levels over time in vivo. The C-terminal lysine residue was found to be rapidly lost in vivo with a half life of about an hour (62 min). In vivo C-terminal lysine processing could be reproduced in vitro, but at a faster rate, by incubating in human serum. Pretreated serum, under conditions used to inactivate carboxypeptidase U, generated in vitro C-terminal lysine processing rates that more closely matched those in vivo. Endogenous IgG, isolated from human blood, contained very low levels of C-terminal lysine (∼0.02%), consistent with the expected circulating half life of antibodies and the calculated C-terminal lysine processing rate. Thus, the low residual IgG2 C-terminal lysine is rapidly processed in vivo and such processing likely occurs on endogenous antibodies in circulation.