gebhart/patrepeval huggingface dataset:
Markerless gene replacement in Escherichia coli stimulated by a double-strand break in the chromosome (1999)

A simple and efficient gene replacement method, based on the recombination and repair activities of the cell, was developed. The method permits the targeted construction of markerless deletions, insertions and point mutations in the Escherichia coli chromosome. A suicide plasmid, carrying the mutant allele and the recognition site of meganuclease I- Sce I, is inserted into the genome by homologous recombination between the mutant and the wild-type (wt) alleles. Resolution of this cointegrate by intramolecular recombination of the allele pair results in either a mutant or a wt chromosome which can be distinguished by allele-specific PCR screening. The resolution process is stimulated by introducing a unique double-strand break (DSB) into the chromosome at the I- Sce I site. Cleavage by the nuclease not only enhances the frequency of resolution by two to three orders of magnitude, but also selects for the resolved products. The DSB-stimulated gene replacement method can be used in recombination-proficient E.coli cells, does not require specific growth conditions, and is potentially applicable in other microorganisms. Use of the method was demonstrated by constructing a 17-bp and a 62-kb deletion in the MG1655 chromosome. Cleavage of the chromosome induces the SOS response but does not lead to an increased mutation rate.
RTL design of 1.2Gbps MIMO WLAN system and its business aspect (2009)

This paper deals with the development of 1.2 Gbps MIMO wireless LAN system based on IEEE802.11TGac's functional requirements. It reaches 33 meter propagation distance by using 80MHz of bandiwdth on 5GHz band. 4 times 5 antennas configuration contribute 2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">nd</sup> -order diversity gain and maintain both the high throughput and the high performance. The proposed Greenfield format preamble has high preamble efficiency. Novel phase rotation is employed to get low PAPR signal of preamble and data fields. Three different coding rates are examined for 64-QAM constellation which all accomplish over 1 Gbps with maximum throughput 1.266 Gbps. Synthesis results indicate that the the prototype system as the initial development of the proposed system can be implemented in target FPGAs of Xilinx Virtex-5 SX240T and LX330T.
Serum Antitoxin Antibodies Mediate Systemic and Mucosal Protection from Clostridium difficile Disease in Hamsters (1999)

Clostridium difficile is the bacterial pathogen identified as the cause of pseudomembranous colitis and is principally responsible for nosocomial antibiotic-associated diarrhea and colitis. The pathologic findings associated with this infection are believed to be caused by two large (approximately 300-kDa) exotoxins, toxins A and B. Because of the mucosal nature of this infection, vaccination strategies aimed at providing prophylactic or therapeutic immune protection have included immunization by mucosal routes. Using the hamster model of C. difficile infection, we examined the protective efficacy of inactivated toxin (toxoid) vaccine formulations prepared as either culture filtrate or partially purified toxoid. We compared combination parenteral and mucosal vaccination regimens involving intranasal, intragastric, or rectal routes of immunization and found that rectal immunization in conjunction with intramuscular (i.m.) vaccination provided full protection of hamsters from death and diarrhea while the other mucosal routes did not. Protection was associated with high levels of toxin-neutralizing antibodies in serum. The requirement for adjuvants for protection was assessed by using sequential i.m. and rectal or i.m. vaccination regimens. Unexpectedly, i.m. immunization without adjuvant conferred the highest protection from death and diarrhea; this regimen elicited the highest serum anti-toxin B titers as well as toxin B neutralizing titers. Passive transfer of mouse antitoxin antibodies protected hamsters in a dose-dependent manner, demonstrating the principal role of circulating antitoxin antibodies in immunity from this toxin-mediated mucosal disease. These results suggest that prophylactic parenteral vaccination or intravenous immunotherapy could provide protection from C. difficile disease in humans.
Bruton Tyrosine Kinase (BTK) and Its Role in B-cell Malignancy (2012)

BTK is a kinase that functions downstream of multiple receptors in various hematologic cells. This review focuses on BTK-dependent pathways that are likely to be involved in maintaining the malignant phenotype in B-cell lymphomas and leukemias. Survival of various B-cell malignancies requires BTK-dependent signals from the B-cell antigen receptor. Survival is also dependent on malignant cells homing to and interacting with lymphoid microenvironments, and these interactions are also BTK-dependent due its role in signaling downstream of chemokine and innate immune receptors. The potential for therapeutic targeting of BTK is currently being tested in clinical settings.
A Nucleosome Positioned in the Distal Promoter Region Activates Transcription of the Human U6 Gene (1997)

To investigate the consequences of chromatin reconstitution for transcription of the human U6 gene, we assembled nucleosomes on both plasmids and linear DNA fragments containing the U6 gene. Initial experiments with DNA fragments revealed that U6 sequences located between the distal sequence element (DSE) and the proximal sequence element (PSE) lead to the positioning of a nucleosome partially encompassing these promoter elements. Furthermore, indirect end-labelling analyses of the reconstituted U6 wild-type plasmids showed strong micrococcal nuclease cuts near the DSE and PSE, indicating that a nucleosome is located between these elements. To investigate the influence that nucleosomes exert on U6 transcription, we used two different experimental approaches for chromatin reconstitution, both of which resulted in the observation that transcription of the U6 wild-type gene was enhanced after chromatin assembly. To ensure that the facilitated transcription of the nucleosomal templates is in fact due to a positioned nucleosome, we constructed mutants of the U6 gene in which the sequences between the DSE and PSE were progressively deleted. In contrast to what was observed with the wild-type genes, transcription of these deletion mutants was significantly inhibited when they were packaged into nucleosomes.
High-quality operation binding for clustered VLIW datapaths (2001)

Clustering is an effective method to increase the available parallelism in VLIW datapaths without incurring severe penalties associated with large number of register file ports. Efficient utilization of a clustered datapath requires careful binding of operations to clusters. The paper proposes a binding algorithm that effectively explores tradeoffs between in-cluster operation serialization and delays associated with data transfers between clusters. Extensive experimental evidence is provided showing that the algorithm generates high quality solutions for basic blocks, with up to 29% improvement over a state-of-the-art advanced binding algorithm.
A major QTL controls susceptibility to spinal curvature in the curveback guppy (2011)

We identify a major QTL that controls susceptibility to curvature. This locus contains over 100 genes, including MTNR1B, a candidate gene for human idiopathic scoliosis. The identification of genes associated with heritable spinal curvature in the curveback guppy has the potential to elucidate the biological basis of spinal curvature among humans and economically important teleosts.
Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven TNF alpha transgenic mice. (1992)

Tumor necrosis factor alpha (TNF alpha) orchestrates a wide range of effects that combat severe infections in animals. At lower levels, TNF alpha plays an important protective role in stimulating chemotaxis and antimicrobial activity of neutrophils, macrophages, and eosinophils. During chronic illness, TNF alpha secretion can be elevated markedly, giving rise to cachexia, hemorrhage, necrosis and, ultimately, death. Although TNF alpha may mediate many of its effects through macrophages, 30% of TNF alpha injected into animals concentrates in the skin. In recent years, it has been shown that keratinocytes can be induced to synthesize TNF alpha. To explore the role of TNF alpha synthesis in keratinocytes, we used a keratin-14 (K14) promoter to target human TNF alpha expression in the epidermis and other stratified squamous epithelia of transgenic mice. Most mice expressing the K14-TNF alpha transgene stopped gaining weight within 1 week postbirth, and exhibited retarded hair growth. In the skin, adipose production was profoundly inhibited, whereas signs of fibrosis and immune infiltration were evident in the dermis. Over time, the epidermis exhibited an increased stratum corneum, as signs of necrosis began to appear in the skin. Within 3-5 weeks, the mice displayed features characteristic of cachexia and necrosis. Our results suggest that TNF alpha expression by keratinocytes not only plays a role in inflammatory and graft-versus-host-disease-like responses in the skin, but also in other tissues, apparently by virtue of stratified squamous epithelial-derived TNF alpha entering the bloodstream. Our results have enabled the first evaluation of many of the effects of TNF alpha in transgenic animals.
New Polyanhydrides Made from a Bile Acid Dimer and Sebacic Acid:  Synthesis, Characterization, and Degradation (2000)

New degradable polyanhydrides have been prepared by polycondensation from a dimer of one of the natural bile acid, lithocholic acid, and by copolymerizing the bile acid dimer with different amounts of sebacic acid (50, 80, and 90 wt %). The homo- and copolymers have shown near zero-order kinetics in the degradation and release studies, carried out in a phosphate buffer environment (pH 7.4) at room temperature. The results showed that the degradation and release rates of the polymers could be adjusted by the copolymer composition. The duration of the samples in the pellet form ranged from several weeks to about 5 years (by extrapolation). No apparent toxicity was observed for the polymer when tested in vivo with cells from normal human and pig tissues. The study showed that these new degradable polymers can be potentially used as controlled release systems.
Application of fuzzy algorithms for control of simple dynamic plant (1974)

The paper describes a scheme in which a fuzzy algorithm is used to control plant, in this case, a laboratory-built steam engine. The algorithm is implemented as an interpreter of a set of rules expressed as fuzzy conditional statements. This implementation on a digital computer is used online, to control the plant. The merit of such a controller is discussed in the light of the results obtained.
The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein (1994)

Adrenoleukodystrophy is a severe genetic demyelinating disease associated with an impairment of beta-oxidation of very long chain fatty acids (VLCFA) in peroxisomes. Earlier studies had suggested that a deficiency in VLCFA CoA synthetase was the primary defect. A candidate adrenoleukodystrophy gene has recently been cloned and was found unexpectedly to encode a putative ATP-binding cassette transporter. We have raised monoclonal antibodies against this protein, that detect a 75kDa band. This protein was absent in several patients with adrenoleukodystrophy. Immunofluorescence and immunoelectron microscopy showed that the adrenoleukodystrophy protein (ALDP) is associated with the peroxisomal membrane. Distinct immunofluorescence patterns were observed in cell lines from patients with Zellweger syndrome (a peroxisomal biogenesis disorder) belonging to different complementation groups.
The Institutional Facets of Innovation Diffusion Initiating: The Case of Wal-Mart's RFID Campaign. (2008)

From two institutional perspectives, we discuss how an organization can initiate the diffusion of a radical IS innovation in its community by proactively exerting institutional influences. Through an in-depth historical analysis, we discuss how Wal-Mart initiated the RFID application in the retailing institutional field. From the institutional field angle, we discuss the structure, the scope, and the institutional carriers of the âRFID in retailâ field in which Wal-Mart initiated the diffusion of RFID. From the institutional strategy angle, we profile Wal-Martâs strategic concerns on RFID diffusion, its interests, and its resources. In the institutionalization processes of the RFID in retail field, we identified that an organizing vision was created, held, and evolved within the field, and played a critical role in Wal-Martâs institutional strategy. By examining institutional perspectives of innovation fostering processes, this paper extends the literature on diffusion of radical IOS innovations in institutional fields.
Polylithiated β-Peptides: like-Selective C-Terminal Alkylation of Boc-β-HVal-β-HAla-β-HLeu-OMe (1998)

A series of N-Boc-protected β-tripeptide derivatives with or without N-methyl groups and with free or Me-ester-protected C terminus has been prepared (8–14, 16, 17). As with α-peptides (→ A), the β-peptide derivatives can be polylithiated (→ B, C). No epimerization of stereogenic centers and no β elimination (exception 17 → 24) is observed upon treatment with bases as strong as tBuLi. The C terminal ester Li-enolate moiety of tetralithio β-tripeptides (cf. C) can be selectively alkylated with methyl, benzyl and allyl halides, and with tert-butyl bromoacetate in yields ranging from 35-80% (8 → 18, 14 → 20–23).
Anti‐B4‐blocked ricin: a phase II trial of 7 day continuous infusion in patients with multiple myeloma (1998)

This phase II trial was undertaken to determine the toxicities, response rate, pharmacokinetics and frequency of human anti-mouse antibody (HAMA) and anti-ricin antibody (HARA) when the B-cell restricted immunotoxin anti-B4-bR was administered to patients with previously treated multiple myeloma (MM). Five patients with MM were scheduled to receive a 7 d continuous infusion of anti-B4-bR. The initial four patients received therapy at 40 microg/kg lean body weight (LBW)/d. Two patients received a 7 d infusion, one patient received 6 d, and another patient 5 d of therapy. The fifth patient was treated for 7 d at a lower dose of 30 microg/kg LBW/d because of the side-effects observed in the initial patients. Pharmacokinetic studies demonstrated a peak serum level >2.6 nM in three of the patients. Side-effects of therapy included hepatic transaminase elevations, myalgias, thrombocytopenia, nausea, vomiting, decrease in performance status, and capillary leak syndrome. One patient developed HAMA and two patients HARA. One patient developed neurologic toxicity with akinetic mutism, and died following therapy. No patient demonstrated a significant decline in M-component during therapy. We concluded that anti-B4-bR can be administered by continuous infusion to patients with multiple myeloma, although immunotoxin levels >3 nM were associated with increased incidence of toxicity and required dose adjustment. Future trials using anti-B4-bR in MM will be needed to determine the optimal dose and administration schedule in this patient population, and to determine whether there is evidence of biologic activity.
Transfer of the virulence plasmid of Yersinia pestis to Yersinia pseudotuberculosis (1985)

Transposon Tn5 insertion derivatives of the virulence plasmid pYV019 of Yersinia pestis were transferred by P1 transduction into a plasmid-free strain of Y. pseudotuberculosis. One of these plasmid derivatives conferred virulence upon the Y. pseudotuberculosis strain. This strain had the ability to express temperature-inducible plasmid-coded outer membrane proteins and was also found to be Ca2+ dependent.
Evaluation Tools and Animal Models of Peripheral Neuropathies (2008)

Peripheral neuropathies are common and frequently debilitating disorders linked to degeneration of peripheral nerves that supply mainly the distal muscles of the extremities. Due to the diverse origin of the pathology (genetic, systemic or environmental), peripheral neuropathies exhibit different clinical forms: acute or chronic, symmetrical or asymmetrical, demyelinating or axonal. In the last 30 years, to gain insight into cellular and molecular mechanisms underlying neuropathies, numerous animal models – either spontaneous or induced by chemical compounds, physical injury or genetic engineering – have been extensively developed and used. In this review, we present (1) the methods used to assess the peripheral neuropathies in the major available animal models and their main pathological characteristics and (2) the main models and their relevance to the human pathology, and, consequently, their usefulness for preclinical studies. Finally, we discuss the emerging, recently developed tools, that should allow to gain a better insight into the mechanisms underlying the peripheral neuropathies.
Correctors of Protein Trafficking Defects Identified by a Novel High‐Throughput Screening Assay (2007)

High-throughput small-molecule screens hold great promise for identifying compounds with potential therapeutic value in the treatment of protein-trafficking diseases such as cystic fibrosis (CF) and nephrogenic diabetes insipidus (NDI). The approach usually involves expressing the mutant form of the gene in cells and assaying function in a multiwell format when cells are exposed to libraries of compounds. Although such functional assays are useful, they do not directly test the ability of a compound to correct defective trafficking of the protein. To address this we have developed a novel corrector-screening assay for CF, in which the appearance of the mutant protein at the cell surface is measured. We used this assay to screen a library of 2000 compounds and have isolated several classes of trafficking correctors that had not previously been identified. This novel screening approach to protein-trafficking diseases is robust and general, and could enable the selection of molecules that could be translated rapidly to a clinical setting.
A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response (2008)

The transcription factor NF-Y is a trimer with histone-like subunits that binds and activates CCAAT-containing promoters. NF-Y controls the expression of several key regulators of the cell cycle. In this study, we examined the functional and molecular effects of NF-YB knockdown. Cell cycle progression is affected with a G2/M-specific depletion. This is due to the inability of activation of G2/M-specific genes, as evidenced by expression profiling, RT-PCR and ChIP data. Surprisingly, apoptosis is also observed, with Caspase 3/7/8 cleavage. A role of p53 and Bcl-2 family members is important. NF-YB inactivation is sufficient to functionally activate p53, in the absence of DNA damage. Failure to maintain a physiologic level of CCAAT-dependent transcription of anti-apoptotic genes contributes to impairment of Bax/Bcl-2 and Bax/Bcl-X(L) ratios. Our data highlight the importance of fine balancing the NF-Y-p53 duo for cell survival by (i) maintaining transcription of anti-apoptotic genes and (ii) preventing p53 activation that triggers the apoptotic cascade.
Monoclonal antibody‐based ELISA to detect glycoprotein tumor‐associated‐antigen‐specific immune complexes in cancer patients (1992)

This report describes the development and applicability of a tumor-associated-antigen-specific immune complex (IC) detection assay to denote the presence of tumor cells in a cancer host. This assay utilizes a murine monoclonal antibody, AD1-40F4, which was produced to a glycoprotein tumor-associated antigen (TAA). In Western blot, the murine monoclonal antibody recognized a 90-100 kD subunit of the antigen. This antigen is immunogenic in cancer patients and induces formation of endogenous antigen-antibody complexes. Analysis of 250 sera from normal individuals and 419 sera from cancer patients revealed that a significantly (P less than .0005) greater proportion (234/419; 55.9%) of cancer sera was positive for the marker than the normal sera (8/250; 3.2%). The incidence of the 90 kD-TAA-specific-IC was consistently and significantly higher in melanoma (58.5%; 38/65), sarcoma (52.9%; 83/157), and carcinoma of breast (50.9%; 58/114), lung (68.2%; 30/44), and colon (64.1%, 25/39) than in the normal group. The age of serum donors did not affect the incidence of the reactivity. Also, at least in the cancer group the gender of the serum donor did not affect the incidence of the 90 kD-TAA-specific-IC positivity. In a retrospective study where sequential serum samples obtained postoperatively from 105 patients with melanoma were analyzed, the 90 kD-TAA-specific-IC could be detected in 72 (69%) of patients several years before the appearance of clinically detectable disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Formation, dynamics, and implication of solid electrolyte interphase in high voltage reversible conversion fluoride nanocomposites (2010)

Metal fluoride nanocomposites are uniquely suited as an alternative pathway to provide very high energy density cathodes for lithium batteries. Contrasted with modern intercalation compounds, they undergo conversion upon discharge into nanodomains of lithium fluoride and highly active metal. The nanosized metal formed during the discharge process along with the dynamic nature of the crystal structure may have considerable impact on the stability of any solid state interphase formed through reaction with the electrolyte. This is in contrast to the more macrocrystalline and stable crystal structure of traditional intercalation compounds. It has been found that the cyclic carbonates are susceptible to decomposition on the nanometal surfaces at potentials as high as 2.00 V vs. Li, and the products have been identified with Field Emission Scanning Electron Microscopy (FESEM), Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), and X-ray Photoelectron Spectroscopy (XPS) as lithium carbonate species. Of greater importance is the impact of these decomposition products on the reversible cycling of the metal fluoride. Through a series of potentiodynamic and galvanostatic cycling trials, a clear relationship has been developed for the bismuth fluoride nanocomposites, the decomposition of the electrolyte solvent, and the cycle life. Acyclic organic carbonate solvents have been found to have minimal interaction and exhibited better long-term cycling performance than cyclic solvents.