gebhart/patrepeval huggingface dataset:
Structural Model of MD-2 and Functional Role of Its Basic Amino Acid Clusters Involved in Cellular Lipopolysaccharide Recognition (2004)

The receptor complex resulting from association of MD-2 and the ectodomain of Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signal transduction across the cell membrane. We prepared a tertiary structure model of MD-2, based on the known structures of homologous lipid-binding proteins. Analysis of circular dichroic spectra of purified bacterially expressed MD-2 indicates high content of beta-type secondary structure, in agreement with the structural model. Bacterially expressed MD-2 was able to confer LPS responsiveness to cells expressing TLR4 despite lacking glycosylation. We identified several clusters of basic residues on the surface of MD-2. Mutation of each of two clusters encompassing the residues Lys(89)-Arg(90)-Lys(91) and Lys(125)-Lys(125) significantly decreased the signal transduction of the respective MD-2 mutants either upon co-expression with TLR4 or upon addition as soluble protein into the supernatant of cells overexpressing TLR4. These basic clusters lie at the edge of the beta-sheet sandwich, which in cholesterol-binding protein connected to Niemann-Pick disease C2 (NPC2), dust mite allergen Der p2, and ganglioside GM2-activator protein form a hydrophobic pocket. In contrast, mutation of another basic cluster composed of Arg(69)-Lys(72), which according to the model lies further apart from the hydrophobic pocket only weakly decreased MD-2 activity. Furthermore, addition of the peptide, comprising the surface loop between Cys(95) and Cys(105), predicted by model, particularly in oxidized form, decreased LPS-induced production of tumor necrosis factor alpha and interleukin-8 upon application to monocytic cells and fibroblasts, respectively, supporting its involvement in LPS signaling. Our structural model of MD-2 is corroborated by biochemical analysis and contributes to the unraveling of molecular interactions in LPS recognition.
Preventing Heat Injuries by Predicting Individualized Human Core Temperature (2015)

Abstract : Heat injury is a problem for the Armed Forces, especially during deployment to localities with very hot and humid climates. Early warning of a rising core body temperature (TC) can help prevent heat injuries. To this end, we developed an algorithm that, given a series of past TC measurements obtained using an ingestible temperature pill, accumulates evidence of a rising TC over time and provides ahead-of-time warning of an impending, dangerously elevated TC. Using data from a cohort of six Soldiers involved in field exercises whose TC exceeded 38.5C, we assessed the performance of the warning algorithm. The algorithm predicted rises in TC with a clinically useful lead time ( 18 min) and reasonable sensitivity and specificity ( 87). However, because ingestible temperature pills are impractical for monitoring a large number of Warfighters during prolonged operations, we developed a mathematical model that uses non-invasive measurements of physiological variables, such as activity (AC), heart rate (HR), and skin temperature, as well as environmental information [ambient temperature (TA) and relative humidity (RH)], to provide individualized real-time TC estimates. Using the same cohort of Soldiers, we evaluated two variants of the individualized model, one that used all the measurements (original model) and another that used AC, HR, and month-average TA and RH values (reduced model). The original and reduced models yielded TC estimates with average errors of 0.31C and 0.35C, respectively, which are within the physiological intra-subject variability of TC. In addition, on average, the estimation time delays ranged from 3 min for the original model to 5 min for the reduced model. We conclude that the individualized TC estimation model can be used to replace ingestible temperature pills and enable the development of a field-deployable early warning system of an impending rise in core temperature.
Mapping of amino acid residues in the C mu 3 domain of mouse IgM important in macromolecular assembly and complement-dependent cytolysis. (1994)

By analyzing the effects of single site mutations of a TNP-binding mouse IgM we have identified amino acid residues clustered in two regions in the C mu 3 domain that are important in the complement-dependent cytolytic activity of polymeric IgM. Some of the mutations also impaired IgM polymerization. For one of these clusters, D432G, P434A, and P436S, which lies on the fy2 and fy3 strands and their connecting loop, polymerization was little affected and the effect on the cytolytic activity of the polymer fraction was taken to imply direct involvement of the residue in C1 binding. The other cluster, involving residues D356A K361A and D417G, is situated at the other end of the C mu 3 domain closer to the center of the Fc mu disc. The D356A K361A and D417G mutations significantly impaired polymer formation, suggesting that these residues are necessary for proper folding or packing of the C mu 3 domains and may affect cytolysis only indirectly. Some other mutations had little or no effect on polymerization or cytolytic activity (E423A, E527G), whereas some mutations impaired only IgM polymerization without affecting cytolytic activity (D344A, K361A, K443A P544G). In others the defect in polymerization was so profound that only the monomer formed (H430A/N/Q and K438G). Our results also suggest that the C1 binding site of IgM is not strictly homologous to the C1 binding site of IgG. Although mutation of E318 of IgG has been shown to reduce its cytolytic activity, mutation of the homologous residue in IgM, E423, was without effect as were mutations of other flanking-charged residues. Proline at 436 in IgM and 331 in IgG may, however, be a common element.
Impedance Characteristics of the Nanoporous Honeycomb Diamond Electrodes for Electrical Double-Layer Capacitor Applications (2001)

Nanoporous boron-doped diamond films with highly ordered pore structures and various pore dimensions, fabricated by oxygen plasma etching of polished polycrystalline diamond films through porous alumina masks, were characterized using electrochemical impedance measurements. The porous structures exhibited wide electrochemical potential windows (2.46-2.70 V), although somewhat less than that for the as-deposited films (3.04 V) because of surface damage due to the oxygen plasma treatment. A film of pore diam 400 nm and pore depth 3 μm exhibited a 400-fold increase in the capacitance in comparison to an as-deposited surface film. A film with 30 nm diam pores showed little enhancement in the capacitance at useful frequencies due to the high pore impedance. Impedance measurements carried out at −0.5 V vs. Ag/AgCl indicated a faradaic reaction, most likely hydrogen evolution. Although the dc current was small (ca. 3.0 μA cm−2 real area for the 60 nm honeycomb), it represents a pathway for charge leakage, limiting the negative potential limit for charge storage. However, similar limits were also observed for a representative acetylene black and activated carbon. The as-deposited diamond and nm honeycomb exhibited significantly higher effective potential limits for anodic charging due to the lack of surface oxidation current. This allows more charge to be stored per unit capacitance for diamond materials than for graphitic carbons. Due to the surface damage, the honeycomb sample did not store as much charge per unit capacitance as the as-deposited sample. © 2001 The Electrochemical Society. All rights reserved.
Single-Stranded DNA Arising at Telomeres in cdc13 Mutants May Constitute a Specific Signal for the RAD9 Checkpoint (1995)

A cdc13 temperature-sensitive mutant of Saccharomyces cerevisiae arrests in the G2 phase of the cell cycle at the restrictive temperature as a result of DNA damage that activates the RAD9 checkpoint. The DNA lesions present after a failure of Cdc13p function appear to be located almost exclusively in telomere-proximal regions, on the basis of the profile of induced mitotic recombination. cdc13 rad9 cells dividing at the restrictive temperature contain single-stranded DNA corresponding to telomeric and telomere-proximal DNA sequences and eventually lose telomere-associated sequences. These results suggest that the CDC13 product functions in telomere metabolism, either in the replication of telomeric DNA or in protecting telomeres from the double-strand break repair system. Moreover, since cdc13 rad9 cells divide at a wild-type rate for several divisions at the restrictive temperature while cdc13 RAD9 cells arrest in G2, these results also suggest that single-stranded DNA may be a specific signal for the RAD9 checkpoint.
Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor. (1999)

We previously reported that both sodium butyrate and trichostatin A (TSA), both of which are known as inhibitors of histone deacetylase, arrest human tumor cells at G1 and G2-M and activate the cyclin-dependent kinase inhibitor, the p21/WAF1/Cip1 gene promoter, through the Sp1 sites. In this study, we identified Sp1 and Sp3 as major factors binding to the Sp1 sites of the p21/WAF1/Cip1 promoter in MG63 cells through electrophoretic mobility shift assays and showed that TSA treatment did not change their binding activities. However, GAL4-Sp3 but not GAL4-Sp1 fusion protein supported the TSA-mediated gene induction from a luciferase reporter plasmid driven by five GAL4 DNA-binding sites. Moreover, the ectopic expression of dominant negative Sp3 repressed the enhancement by TSA of the p21/WAF1/Cip1 promoter and Sp1 site-driven promoter. Taken together, these results suggest that histone deacetylase inhibitor up-regulates p21/WAF1/Cip1 transcription by Sp3 but not by Sp1.
Inhibition of lipid synthesis by beta beta'-tetramethyl-substituted, C14-C22, alpha, omega-dicarboxylic acids in cultured rat hepatocytes. (1985)

beta beta'-Methyl-substituted, C14-C18, alpha, omega-dicarboxylic acids (MEDICA 14-18) were found to inhibit fatty acids and cholesterol synthesis in cultured rat hepatocytes. Maximum inhibition was observed with MEDICA 16, amounting to a 50% decrease in 3H2O and acetate incorporation into fatty acids and cholesterol in the presence of 0.08 mM of the drug added to the culture medium. Inhibition of lipogenesis was not accompanied by inhibition of palmitate or glycerol esterification into neutral lipids and phospholipids. The respective capacities of MEDICA homologues of varying acyl chain length as inhibitors of fatty acid and cholesterol synthesis in cultured rat hepatocytes and in vivo (Bar-Tana, J., Rose-Kahn, G., and Srebnik, M. (1985) J. Biol. Chem. 260, 8404-8410) correlated well with their respective inhibitory effect on liver ATP-citrate lyase. Thus, MEDICA 16 inhibited liver ATP-citrate lyase competitively to citrate with a Ki of 16 microM as compared to a Km of 0.8 mM for the citrate substrate.
PEAR: a fast and accurate Illumina Paired-End reAd mergeR (2013)

PEAR is implemented in C and uses POSIX threads. It is freely available at http://www.exelixis-lab.org/web/software/pear.
Autoantibodies to GABA-ergic Neurons and Pancreatic Beta Cells in Stiff-Man Syndrome (1990)

Stiff-man syndrome is a rare disorder of the central nervous system of unknown pathogenesis. We have previously reported the presence of autoantibodies against glutamic acid decarboxylase (GAD) in a patient with stiff-man syndrome, epilepsy, and insulin-dependent diabetes mellitus. GAD is an enzyme selectively concentrated in neurons secreting the neurotransmitter gamma-aminobutyric acid (GABA) and in pancreatic beta cells. We subsequently observed autoantibodies to GABA-ergic neurons in 20 of 33 patients with stiff-man syndrome. GAD was the principal autoantigen. In the group of patients positive for autoantibodies against GABA-ergic neurons, there was a striking association with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus. These findings support the hypothesis that stiff-man syndrome is an autoimmune disease and suggest that GAD is the primary autoantigen involved in stiff-man syndrome and the associated insulin-dependent diabetes mellitus. Our findings also indicate that autoantibodies directed against GABA-ergic neurons are a useful marker in the diagnosis of the disease.
Remodeling Chromatin and Stress Resistance in the Central Nervous System: Histone Deacetylase Inhibitors as Novel and Broadly Effective Neuroprotective Agents (2005)

Acetylation and deacetylation of histone protein plays a critical role in regulating gene expression in a host of biological processes including cellular proliferation, development, and differentiation. Accordingly, aberrant acetylation and deacetylation resulting from the misregulation of histone acetyltransferases (HATs) and/or histone deacetylases (HDACs) has been linked to clinical disorders such as Rubinstein-Taybi syndrome, fragile X syndrome, leukemia, and various cancers. Of significant import has been the development of small molecule HDAC inhibitors that permit pharmacological manipulation of histone acetylation levels and treatment of some of these diseases including cancer. In this Review we discuss evidence that aberrant HAT and HDAC activity may also be a common underlying mechanism contributing to neurodegeneration during acute and chronic neurological diseases, including stroke, Huntington's disease Amyotrophic Lateral Sclerosis and Alzheimer's disease. With this in mind, a number of studies examining the use of HDAC inhibitors as therapy for restoring histone acetylation and transcriptional activation in in vitro and in vivo neurodegenerative models are discussed. These studies demonstrate that pharmacological HDAC inhibition is a promising therapeutic approach for the treatment of a range of central nervous system disorders.
Therapeutic HPV Cancer Vaccine Targeted to CD40 Elicits Effective CD8+ T-cell Immunity (2016)

Human papillomavirus (HPV), particularly HPV16 and HPV18, can cause cancers in diverse anatomical sites, including the anogenital and oropharyngeal (throat) regions. Therefore, development of safe and clinically effective therapeutic vaccines is an important goal. Herein, we show that a recombinant fusion protein of a humanized antibody to CD40 fused to HPV16.E6/7 (αCD40-HPV16.E6/7) can evoke HPV16.E6/7-specific CD8<sup>+</sup> and CD4<sup>+</sup> T-cell responses in head-and-neck cancer patients in vitro and in human CD40 transgenic (hCD40Tg) mice in vivo The combination of αCD40-HPV16.E6/7 and poly(I:C) efficiently primed HPV16.E6/7-specific T cells, particularly CD8<sup>+</sup> T cells, in hCD40Tg mice. Inclusion of montanide enhanced HPV16.E6/7-specific CD4<sup>+</sup>, but not CD8<sup>+</sup>, T-cell responses. Poly(I:C) plus αCD40-HPV16.E6/7 was sufficient to mount both preventative and therapeutic immunity against TC-1 tumors in hCD40Tg mice, significantly increasing the frequency of HPV16-specific CD8<sup>+</sup> CTLs in the tumors, but not in peripheral blood. In line with this, tumor volume inversely correlated with the frequency of HPV16.E6/7-specific CD8<sup>+</sup> T cells in tumors, but not in blood. These data suggest that CD40-targeting vaccines for HPV-associated malignancies can provide a highly immunogenic platform with a strong likelihood of clinical benefit. Data from this study offer strong support for the development of CD40-targeting vaccines for other cancers in the future. Cancer Immunol Res; 4(10); 823-34. ©2016 AACR.
Isolation of Cadmium-Tolerant Bacteria and Characterization of Cadmium Accumulation into the Bacteria Cell (1992)

Of the cadmium-tolerant 162 bacterial strains isolated from soils, river waters or active sludges of waste-water disposal plants in the Gyeongnam province a strain C1, which showed considerably higher growth rate in the agar plate containing 2000 ppm than any other strains isolated, was identified as a Pseudomonas putida or its similar strain when analyzed by taxonomical characteristics. Optimum pH and temperature for the growth of the P, putida were 7.0 and , respectively. This strain was resistant to antibiotics(ampicillin, chloramphenicol and streptomycin), and heavy metals(lithium, cupper, lead and zinc). This strain utilized salicylate, naphthalene or xylene as a sole carbon source. The rate of cadmium accumulation in P. putida cell was enhanced at low concentration of Cd in the growth media. The maximum cadmium absorption by this strain grown in 1 and l0ppm of Cd was respectively 78% and 60% 24 hrs after culture, but in 100 ppm Cd, 40% 48 hrs after culture. Addition of a non-ionic surfactant Triton X-100(0.1%) to the medium enhanced the accumulation of cadmium in the P. putida up to approximately 37%.
Heterogeneity of monoclonal antibody-reactive epitopes on mycobacterial 30-kilodalton-region proteins and the secreted antigen 85 complex and demonstration of antigen 85B on the Mycobacterium leprae cell wall surface (1992)

Proteins of the antigen 85 complex in the 30-kDa region secreted by live mycobacteria are important in the immune response against mycobacterial infections and may play an important biological role in the host-parasite interaction. In the present study, we have characterized epitopes of the 30-kDa-region proteins and the antigen 85 complex by using a panel of 13 monoclonal antibodies (MAbs) reacting with these antigens, 6 of which have not been described before. By using five previously characterized related secreted proteins of Mycobacterium tuberculosis, MPT44 (85A), MPT59 (85B), MPT45 (85C), MPT51 (27 kDa), and MPT64 (26 kDa), we have identified at least 10 different MAb-reactive epitopes on the proteins of the antigen 85 complex. A heterogeneous distribution of epitopes was observed within the components of the antigen 85 complex. Two distinct epitopes specific for antigen 85B and two other epitopes restricted to the 85A and 85B components were recognized. Two of them were shared with a previously unidentified 27-kDa protein present in M. tuberculosis culture fluid from which all MPT proteins were derived. The rest of the MAb-reactive epitopes were found to be present mostly in antigens 85A and 85B and to a lesser extent in antigen 85C. None of these MAbs recognized component 85C alone nor did they bind to the related MPT51 and MPT64 proteins. Interestingly, most of the MAbs reacted with purified native proteins of the antigen 85 complex but not to them in their denatured forms. In contrast, reactivity of the MAbs with the cytosol fraction of M. tuberculosis in immunoblotting revealed that they bound to a closely related cytosolic 30-kDa protein(s) even when they were denatured. Heterogeneity of these MAb-reactive epitopes of the antigen 85 complex was further evident as they were found to be distributed in various patterns among 19 different mycobacterial species. By using fusion proteins of the Mycobacterium leprae 30/31-kDa antigen 85 complex, we have localized at least six different epitopes within amino acid residues 55 to 266 of the M. leprae antigen 85 complex. Finally, by immunohistochemical analysis, we have demonstrated the in situ expression of one of the novel MAb-reactive epitopes specific for antigen 85B on the cell wall surface of M. leprae within macrophages in lepromatous leprosy lesions and thus provide direct evidence for the presence of the B component of the antigen 85 complex on the surface of intact M. leprae.
Mouse Anti‐human Interleukin‐6 Receptor Monoclonal Antibody Inhibits Proliferation of Fresh Human Myeloma Cells in vitro (1994)

Interleukin-6 (IL-6) is a major growth factor in multiple myeloma. We investigated the effect of mouse anti-human IL-6 receptor monoclonal antibody (anti-IL-6R mAb) on the in vitro proliferation of freshly isolated myeloma cells from 21 patients to evaluate the therapeutic potential. The addition of anti-IL-6R mAb inhibited more than 30% of the spontaneous proliferation of myeloma cells in 9 of 21 cases in a dose- (0.1 to 20 micrograms/ml) and time-dependent manner. The inhibitory effects of anti-IL-6R mAb did not differ significantly from that of anti-IL-6 mAb, and were correlated with the extent of the response of myeloma cells to IL-6. Flow cytometric analysis showed that all myeloma cells expressed IL-6R, whose intensity was not correlated with either the extent of response of myeloma cells to IL-6 or the inhibitory effects of anti-IL-6R mAb on proliferation of myeloma cells. Although our study showed heterogeneity in the proliferative responses of myeloma cells to IL-6 and anti-IL-6R mAb, these observations suggest the possibility of using anti-IL-6R mAbs for treating some patients with multiple myeloma whose growth depends on IL-6.
Vocabulary Teaching Methods for Beginners and Intermediate Level Students in TCSL (2012)

This paper puts forward the importance and necessity of vocabulary teaching in TCSL and the methods of teaching Chinese characters and words to international students of elementary and intermediate levels. This paper consists of four parts: introduction, importance and necessity of teaching Chinese characters and words in Teaching Chinese as a Second Language (TCSL), methods of teaching Chinese characters and words to international students, conclusion and implications.
The glucose distribution in 9l rat brain multicell tumor spheroids and its effect on cell necrosis (1982)

The glucose consumption rate of 9L rat brain tumor cells was determined as a function of concentration. Glucose uptake followed Michaelis-Menten kinetics with a Km of 0.58 mM and a vmax of 1.6 pg/cellmin. The glucose diffusion coefficient in spheroids of 9L tumor cells was determined to be 1.5 × 10−6 cm2/s at 37°C. Using these parametric values, the glucose distribution in 9L multicell spheroids was calculated and related to the viable and necrotic zones.
Dynamic dispatch in object-oriented languages (1994)

Dynamic binding in object-oriented languages is perhaps the most important semantic aspect of these languages. At the same time it can contribute to inefficiency and lack of robustness because it incurs lookup overheads on function calls and hinders the compiler determining the exact type of objects held in variables or returned by functions. This may, for instance, preclude inlining of small functions or attribute offset computation at compile time. Yet attribute accesses are the most frequently executed operations. As a result, to regain lost performance, OO programmers are tempted to break the encapsulation of classes or want explicit control over dynamic dispatch, trading off extensibility. In the implementation of parallel object-oriented languages the additional complication arises that object accesses may require more expensive remote memory accesses. Lookup at the call may be inappropriate if the code has to be executed on a different processor and there perhaps has a different address. This paper summarizes dispatching as addressed in several modern object-oriented languages. We then describe and benchmark fast and exible dispatch schemes that we are currently implementing on SPARC based workstations and multi-processors. These involve elements of C++ virtual function tables and Eiffel's and Sather's ability to redefine abstract functions as attributes. Initial benchmarks seem to promise improved efficiency on a range of modern RISC based architectures.