gebhart/patrepeval huggingface dataset:
srf-3, a Mutant of Caenorhabditis elegans, Resistant to Bacterial Infection and to Biofilm Binding, Is Deficient in Glycoconjugates (2004)

srf-3 is a mutant of C. elegans that is resistant to infection by Microbacterium nematophilum and to binding of the biofilm produced by Yersinia pseudotuberculosis and Yersinia pestis. Recently, SRF-3 was characterized as a nucleotide sugar transporter of the Golgi apparatus occurring exclusively in hypodermal seam cells, pharyngeal cells, and spermatheca. Based on the above observations, we hypothesized that srf-3 may have altered glyconjugates that may enable the mutant nematode to grow unaffected in the presence of the above pathogenic bacteria. Following analyses of N- and O-linked glycoconjugates of srf-3 and wild type nematodes using a combination of enzymatic degradation, permethylation, and mass spectrometry, we found in srf-3 a 65% reduction of acidic O-linked glycoconjugates containing glucuronic acid and galactose as well as a reduction of N-linked glycoconjugates containing galactose and fucose. These results are consistent with the specificity of SRF-3 for UDP-galactose and strongly suggest that the above glycoconjugates play an important role in allowing adhesion of M. nematophilum or Y. pseudotuberculosis biofilm to wild type C. elegans. Furthermore, because seam cells as well as pharyngeal cells secrete their glycoconjugates to the cuticle and surrounding surfaces, the results also demonstrate the critical role of these cells and their secreted glycoproteins in nematode-bacteria interactions and offer a mechanistic basis for strategies to block such recognition processes.
Islet gene expression and function in type 2 diabetes; studies in the Goto‐Kakizaki rat and humans (2007)

Defective beta-cell function with resulting impairment of glucose-stimulated insulin release is a critical factor in the pathogenesis of type 2 diabetes. Accumulated studies in pancreatic islets of the spontaneously diabetic Goto-Kakizaki (GK) rat suggest that this is a useful animal model of type 2 diabetes. The GK rat is non-obese, and abnormal glucose regulation develops early in life in association with impaired insulin secretion. There are some differences in islet morphology and function reported between different GK rat colonies. In addition to reduction of beta-cell mass, a number of beta-cell defects have been described with possible relevance for the reduced insulin secretion. Interestingly, some of these defects have also been shown in isolated islets from type 2 diabetic humans. The polygenic nature of diabetes heredity in the GK rat may well resemble the genetic basis in the majority of patients with type 2 diabetes. Here, we review studies concerning beta-cell function and islet gene expression in the GK rat and compare it with the limited number of investigations on similar topics in isolated islets from patients with type 2 diabetes.
Microstructure of AA7075 Based Composite by Accumulative Roll Bonding Process (2015)

Accumulative Roll Bonding (ARB) is a Severe Plastic Deformation (SPD) process invented in order to fabricate ultrafine grained materials. Aluminum Alloy series 7075 (AA7075) is a metal as a matrix reinforced by Alumina Nanofiber (ANF). In the development of advanced materials, AA7075/ANF composite metal is very suitable if it is processed by ARB, due to the combination of high style roll that is capable of producing material properties better. Hardness of AA77075 without reinforcement reached 128.3 Hv 10 . The additions of ANF on AA7075 reduce the hardness of 103.2 Hv 10 . This is due to large deformation of high load on the ARB which results in decrease levels of precipitates as well as lower density and reduction in the average grain size.
Benzoylurea pesticides used as veterinary medicines in aquaculture: Risks and developmental effects on nontarget crustaceans (2015)

Diflubenzuron and teflubenzuron are benzoylureas that are used in aquaculture to control sea lice. Flubenzurons have low toxicity to many marine species such as fish and algae but by their nature are likely to have significant adverse effects on nontarget species such as crustaceans and amphipods. Although the exact mechanism of toxicity is not known, these compounds are thought to inhibit the production of the enzyme chitin synthase during molting of immature stages of arthropods. These chitin synthesis inhibitors are effective against the larval and pre-adult life stages of sea lice. Due to their low solubility and results of recent monitoring studies conducted in Norway, the sediment compartment is considered the most likely reservoir for these compounds and possible remobilization from the sediment to benthic crustaceans could be of importance. For this reason, the epibenthic copepod Tisbe battagliai was selected for investigations into the acute and developmental effects of these compounds. For comparative purposes, azamethiphos was investigated to identify differences in sensitivity and act as a negative control for developmental effects at environmentally relevant concentrations. Standard acute studies with adult copepods showed little or no acute toxicity at milligrams per liter levels with the flubenzurons, whereas a naupliar developmental test demonstrated that environmentally relevant concentrations (e.g., nanograms per liter) caused a complete cessation of molting and finally death in the exposed copepods.
Combination Therapy Targeting BCL6 and Phospho-STAT3 Defeats Intratumor Heterogeneity in a Subset of Non–Small Cell Lung Cancers (2017)

Oncogene-specific changes in cellular signaling have been widely observed in lung cancer. Here, we investigated how these alterations could affect signaling heterogeneity and suggest novel therapeutic strategies. We compared signaling changes across six human bronchial epithelial cell (HBEC) strains that were systematically transformed with various combinations of <i>TP53, KRAS</i>, and <i>MYC</i>-oncogenic alterations commonly found in non-small cell lung cancer (NSCLC). We interrogated at single-cell resolution how these alterations could affect classic readouts (β-CATENIN, SMAD2/3, phospho-STAT3, P65, FOXO1, and phospho-ERK1/2) of key pathways commonly affected in NSCLC. All three oncogenic alterations were required concurrently to observe significant signaling changes, and significant heterogeneity arose in this condition. Unexpectedly, we found two mutually exclusive altered subpopulations: one with STAT3 upregulation and another with SMAD2/3 downregulation. Treatment with a STAT3 inhibitor eliminated the upregulated STAT3 subpopulation, but left a large surviving subpopulation with downregulated SMAD2/3. A bioinformatics search identified <i>BCL6</i>, a gene downstream of SMAD2/3, as a novel pharmacologically accessible target of our transformed HBECs. Combination treatment with STAT3 and BCL6 inhibitors across a panel of NSCLC cell lines and in xenografted tumors significantly reduced tumor cell growth. We conclude that BCL6 is a new therapeutic target in NSCLC and combination therapy that targets multiple vulnerabilities (STAT3 and BCL6) downstream of common oncogenes, and tumor suppressors may provide a potent way to defeat intratumor heterogeneity. <i>Cancer Res; 77(11); 3070-81. ©2017 AACR</i>.
Combinatorial Effect of Two Framework Mutations (E119V and I222L) in the Neuraminidase Active Site of H3N2 Influenza Virus on Resistance to Oseltamivir (2011)

Neuraminidase (NA) inhibitors (NIs) are the first line of defense against influenza virus. Reverse genetics experiments allow the study of resistance mechanisms by anticipating the impacts of mutations to the virus. To look at the possibility of an increased effect on the resistance phenotype of a combination of framework mutations, known to confer resistance to oseltamivir or zanamivir, with limited effect on virus fitness, we constructed 4 viruses by reverse genetics in the A/Moscow/10/99 H3N2 background containing double mutations in their neuraminidase genes: E119D+I222L, E119V+I222L, D198N+I222L, and H274Y+I222L (N2 numbering). Among the viruses produced, the E119D+I222L mutant virus was not able to grow without bacterial NA complementation and the D198N+I222L mutant and H274Y+I222L mutant were not stable after passages in MDCK cells. The E119V+I222L mutant was stable after five passages in MDCK cells. This E119V-and-I222L combination had a combinatorial effect on oseltamivir resistance. The total NA activity of the E119V+I222L mutant was low (5% compared to that of the wild-type virus). This drop in NA activity resulted from a decreased NA quantity in the virion in comparison to that of the wild-type virus (1.4% of that of the wild type). In MDCK-SIAT1 cells, the E119V+I222L mutant virus did not present a replicative advantage over the wild-type virus, even in the presence of oseltamivir. Double mutations combining two framework mutations in the NA gene still have to be monitored, as they could induce a high level of resistance to NIs, without impairing the NA affinity. Our study allows a better understanding of the diversity of the mechanisms of resistance to NIs.
Malabsorption During and After Recovery from Acute Intestinal Infection (1965)

Amer. Rev. resp. Dis., 1963, 88, part 2. Badger, G. F., Dingle, J. H., Feller, A. E., Hodges, R. G., Jordan, W. S., jun., and Rammelkamp, C. H., jun. (1953). Amer. J. Hyg., 58, 174. Banatvala, J. E., Anderson, T. B., and Reiss, B. B. (1964). Brit. med. J.y 1, 537. Buck, C. (1956). Amer. J. Hyg., 63, 1. Chanock, R. M., Bell, J. A., and Parrott, R. H. (1961). In Perspectives in Virology, edited by M. Pollard, 2, 126. Chapman and Hall, London. Parrott, R. H., Cook, K., Andrews, B. E., Bell, J. A., Reichelderfer, T., Kapikian, A. Z., Mastrota, F. M., and Huebner, R. J. (1958). New Engl. J. Med., 258, 207. Clarke, S. K. R., Corner, B. D., Gambier, D. M., Macrae, J., and Peacock, D. B. (1964). Brit. med. J., 1, 1536. Dimmock, N. J., and Tyrrell, D. A. J. (1962). Lancet, 2, 536. Gamble, D. R., and Kinsley, M. L. (1963). Mth. Bull. Minist. Hlth Lab. Serv., 22, 6. Gardner, P. S., Stanfield, J. P., Wright, A. E., Court, S. D. M., and Green, C A. (1960). Brit. med. J., 1, 1077. Higgins, P. G., Boston, D. G., and Ellis, E. M. (1964). Mth. Bull. Minist. Hlth Lab. Serv., 23, 93. Ellis, E. M., and Boston, D. G. (1963). Ibid., 22, 71. Holzel, A., Parker, L., Patterson, W. H., Cartmel, D., White, L. L. R Purdy, R., Thompson, K. M., and Tobin, J. O'H. (1965). Brit. mea. J., 1, 614. Kendall, E. J. C, Bynoe, M. L., and Tyrrell, D. A. J. (1962). Ibid., 2 82 Lidwell, ?. M., and Sommerville, T. (1951). J. Hyg. (Lond.), 49, 365. Peacock, D. B., and Clarke, S. K. R. (1961). Lancet, 2, 466. Sutton, R. N. P. (1962). J. Hyg. (Lond.), 60, 51. Tyrrell, D. A. J. (1963). Amer. Rev. resp. Dis., 88, part 2, p. 77. and Parsons, R. (1960). Lancet, 1, 239.
Mutant <i> Ikzf1, Kras <sup>G12D</sup> </i> , and <i>Notch1</i> cooperate in T lineage leukemogenesis and modulate responses to targeted agents (2010)

Mice that accurately model the genetic diversity found in human cancer are valuable tools for interrogating disease mechanisms and investigating novel therapeutic strategies. We performed insertional mutagenesis with the MOL4070LTR retrovirus in Mx1-Cre, Kras G12D mice and generated a large cohort of T lineage acute lymphoblastic leukemias (T-ALLs). Molecular analysis infers that retroviral integration within Ikzf1 is an early event in leukemogenesis that precedes Kras G12D expression and later acquisition of somatic Notch1 mutations. Importantly, biochemical analysis uncovered unexpected heterogeneity, which suggests that Ras signaling networks are remodeled during multistep tumorigenesis. We tested tumor-derived cell lines to identify biomarkers of therapeutic response to targeted inhibitors. Whereas all T-ALLs tested were sensitive to a dual-specificity phosphoinosityl 3-kinase/mammalian target of rapamycin inhibitor, biochemical evidence of Notch1 activation correlated with sensitivity to γ-secretase inhibition. In addition, Kras G12D T-ALLs were more responsive to a MAP/ERK kinase inhibitor in vitro and in vivo. Together, these studies identify a genetic pathway involving Ikzf1, Kras G12D , and Notch1 in T lineage leukemogenesis, reveal unexpected diversity in Ras-regulated signaling networks, and define biomarkers of drug responses that may inform treatment strategies.
Comparison in Chemical Composition of Cell Walls of Glycine- Sensitive- and Resistant Strains of Bacillus subtilis (1964)

A glycine-resistant strain of Bacillus subtilis was obtained after several time-subcultures of glycine-sensitive parent in a glycine-containing medium, and comparison in the chemical composition of cell wall was made between both strains. The major amino acid components were alanine, glutamic and diaminopimelic acid. Glucose, rhamnose, glucosamine and muramic acid were also found as the common sugar components in both cell walls. However, muramic acid in the cell wall of resistant strain was significantly less than that in the sensitive parent. Also, galactose and galactosamine were found only in the wall preparation of the resistant cells.
A human-interactive robotic program for middle school STEM education (2017)

The use of human-interactive robots in industry and daily life has become more prevalent throughout society as more people are using collaborative, and assistive robots to accomplish a task. To demonstrate the utility and importance of assistive robots to middle school students, a unique educational platform called Neu-pulator (neurally-controlled manipulator) was designed and fabricated to introduce their application in improving the quality of life. This robotic manipulator consists of low-cost components, which reflect the characteristics of a human arm, and is actuated by signals from the students neuromuscular system. During summer 2016, a 5-day program introduced students to the engineering design process as they designed, programmed, manufactured, and tested the Neu-pulator robot. A series of surveys and group interviews were performed to understand how each students attitude and opinion towards different STEM-related topics evolved throughout the course, both quantitatively and qualitatively. We observed that the students confidence, attitude, and excitement towards STEM improved over the course of the week, especially when they could see the robot they developed in action. With the use of this unique educational platform, a bridge can be made from learning fundamental STEM concepts to real-world application of human interactive and assistive robots.
Local nasal immunotherapy in allergic rhinitis to <i>Parietaria</i> (1992)

Preseasonal local nasal immunotherapy (LNIT) by means of an extract in macronized powder form has been studied in allergic rhinitis to parietaria. Twenty-four Parietaria-sensitive patients have been studied for 18 weeks in a double-blind controlled trial. Subjects were selected on the basis of a positive skin test, RAST and intranasal challenge to Parietaria antigen. Three eight-patient groups were randomly planned: the first group was given native Parietaria product, the second modified Parietaria product, and the third placebo. During the pollen season no difference was observed in mean weekly symptom score between the three groups, while the mean weekly medication score was significantly lower in the treated groups than the control group. Only the treated groups showed a significant increase in specific nasal threshold to Parietaria after treatment. Adverse reactions to LNIT, limited to the upper respiratory tract, occurred rarely and did not interfere with the dose schedule. This study indicates that LNIT in powder form may be a suitable alternative to the traditional subcutaneous immunotherapy in terms of clinical efficacy and safety.
Characterization of non equilibrium effects on high quality critical flows (1995)

The appropriate design of various pieces of safety equipment such as relief systems, relies on the accurate description of critical flow phenomena. Most of the systems of industrial interest are willing to be described by one-dimensional area-averaged models and a large fraction of them involves multi-component high gas quality flows. Within these circumstances, the flow is very likely to be of an annular dispersed nature and its description by two-fluid models requires various closure relations. Among the most sensitive closures, there is the interfacial area and the liquid entrained fraction. The critical flowrate depends tremendously on the accurate description of the non equilibrium which results from the correctness of the closure equations. In this study, two-component flows are emphasized and non equilibrium results mainly form the differences in the phase velocities. It is therefore of the utmost importance to have reliable data to characterize non equilibrium phenomena and to assess the validity of the closure models. A comprehensive description of air-water nozzle flows, with emphasis on the effect of the nozzle geometry, has been undertaken and some of the results are presented here which helps understanding the overall flow dynamics. Besides the critical flowrate, the presented material includes pressure profiles, droplet size and velocity, liquid film flowrate and liquid film thickness.
Unlocking the Power of Formal Hardware Verification with CoSA and Symbolic QED: Invited Paper (2019)

As designs grow in size and complexity, design verification becomes one of the most difficult and costly tasks facing design teams. Formal verification techniques offer great promise because of their ability to exhaustively explore design behaviors. However, formal techniques also have a reputation for being labor-intensive and limited to small blocks. Is there any hope for successful application of formal techniques at design scale? We answer this question affirmatively by digging deeper to understand what the real technological issues and opportunities are. First, we look at satisfiability solvers, the engines underlying formal techniques such as model checking. Given the recent innovations in satisfiability solving, we argue that there are many reasons to be optimistic that formal techniques will scale to designs of practical interest. We use our CoSA model checker as a demonstration platform to illustrate how advances in solvers can improve scalability. However, even if solvers become blazingly fast, applying them well is still labor-intensive. This is because formal tools are only as useful as the properties they are given to prove, which traditionally have required great effort to develop. Symbolic quick error detection (SQED) addresses this issue by using a single, universal property that checks designs automatically. We demonstrate how SQED can automatically find logic and security bugs in a variety of designs and report on bugs found and efficiency gains realized in academic and industry designs. We also present a generator for an improved SQED module that further reduces the amount of manual effort that has to be spent by the designer.
Autoimmunity and HCV infection in porphyria cutanea tarda: a controlled study. (2002)

Autoimmunity and high rates of autoantibodies have been implicated in the pathogenesis of porphyria cutanea tarda. These abnormalities could be in part virus-induced, since porphyria cutanea tarda in most geographical regions is highly associated with hepatitis C virus infection. We analyzed the link of autoantibodies, autoimmune hepatitis and systemic lupus erythematosus in 111 patients with porphyria cutanea tarda and sex- and age-matched controls (mean age 58+/-13 years) in Germany, a region with a low prevalence of hepatitis C virus infection. Patients with porphyria cutanea tarda displayed lower rates of anti-nuclear antibodies (16/111, 14% vs 28/111, 25%, p<0,05) and of antibodies against smooth muscle (25/111, 23% vs 48/111, 43%, p<0,01), than controls. The percentage of patients with porphyria cutanea tarda with positive anti-HCV was low but significantly higher than in our controls (9/111, 8% vs 0/111, 0%, respectively), (p<0,05). Two patients with porphyria cutanea tarda (2/111, 2%) fulfilled the criteria for systemic lupus erythematosus and not one of 65 patients was found to have clinical autoimmune hepatitis. In the first controlled study of a large cohort of patients with porphyria cutanea tarda no increased prevalence of selected autoantibodies and autoimmune hepatitis was found. However, a higher prevalence of HCV infection and systemic lupus erythematosus in patients with porphyria cutanea tarda was confirmed.
A 5G Architecture for The Factory of the Future (2018)

Factory automation and production are currently undergoing massive changes, and 5G is considered being a key enabler. In this paper, we state uses cases for using 5G in the factory of the future, which are motivated by actual needs of the industry partners of the "5Gang" consortium. Based on these use cases and the ones by 3GPP, a 5G system architecture for the factory of the future is proposed. It is set in relation to existing architectural frameworks.
C2 Domain Protein MIN1 Promotes Eyespot Organization in<i>Chlamydomonas reinhardtii</i> (2008)

Assembly and asymmetric localization of the photosensory eyespot in the biflagellate, unicellular green alga Chlamydomonas reinhardtii requires coordinated organization of photoreceptors in the plasma membrane and pigment granule/thylakoid membrane layers in the chloroplast. min1 (mini-eyed) mutant cells contain abnormally small, disorganized eyespots in which the chloroplast envelope and plasma membrane are no longer apposed. The MIN1 gene, identified here by phenotypic rescue, encodes a protein with an N-terminal C2 domain and a C-terminal LysM domain separated by a transmembrane sequence. This novel domain architecture led to the hypothesis that MIN1 is in the plasma membrane or the chloroplast envelope, where membrane association of the C2 domain promotes proper eyespot organization. Mutation of conserved C2 domain loop residues disrupted association of the MIN1 C2 domain with the chloroplast envelope in moss cells but did not abolish eyespot assembly in Chlamydomonas. In min1 null cells, channelrhodopsin-1 (ChR1) photoreceptor levels were reduced, indicating a role for MIN1 in ChR1 expression and/or stability. However, ChR1 localization was only minimally disturbed during photoautotrophic growth of min1 cells, conditions under which the pigment granule layers are disorganized. The data are consistent with the hypothesis that neither MIN1 nor proper organization of the plastidic components of the eyespot is essential for localization of ChR1.
Optical resolution through diastereomeric salt formation: the crystal structures of cinchoninium (<i>R</i>)-mandelate and cinchoninium (<i>S</i>)-mandelate at low temperature (1993)

The crystal structures of the diastereomeric salts formed between cinchonine and mandelic acid have been analysed. The more soluble of the two salts is cinchoninium (S)-mandelate, C19H23N20 +.C8H703--, Mr = 446.55, monoclinic, P21, T= 110 (1) K, a = 11.2478(10), b=7.0880(6), c=14.684(2) A, /3= 99.068 (7) °, V = 1156.0 (4)/~3, Z = 2, Ox = 1.283 g cm -3, A(Cu Ka) = 1.54184 A, # = 6.57cm-1, F(000)=476, R=0.029 for 2338 observed reflections. The less soluble salt is cinchoninium (R)-mandelate, CI9H23N20 +.CSH7Of, Mr = 446.55, orthorhombic, P212121, T = 122.0 (5)K, a = 12.078 (4), b = 17.423 (2), c = 22.136 (4),~, V= 4658 (3) A 3, z = 8, Dx = 1.273 gcm- 3, A(Cu Ka) = 1.54184 ,~, /1, = 6.52 cm- ~, F(000) = 1904, R = 0.055 for 4125 observed reflections. In the (R)-mandelate salt one of the two independent cinchoninium cations displays disorder of the --CH=CH2 moiety. Apart from variations in the conformation of the vinyl group the cinchoninium cations are alike. The difference in conformation of the (R)- and (S)mandelate ions can be related to differences in the hydrogen-bonding systems. Interionic interactions in the S salt stabilize it relative to the R salt. The differences in the melting enthalpies and entropies of the two diastereomeric salts are related to their structural differences.