gebhart/patrepeval huggingface dataset:
Mutational analysis of an Escherichia coli fourteen-gene operon for phosphonate degradation, using TnphoA' elements (1993)

All genes for phosphonate (Pn) utilization in Escherichia coli are in a large cluster of 14 genes named, in alphabetical order, phnC to phnP. Plasmids carrying these genes were mutagenized by using TnphoA'-1, and 43 mutants containing simple insertions were studied in detail. Their insertion sites were defined by restriction mapping and by DNA sequencing. One or more mutations in each phn gene was identified. In 23 mutants, expression of the TnphoA'-1 lacZ gene was phosphate starvation inducible. These mutants had TnphoA'-1 oriented in line behind the phnC promoter, i.e., in the + orientation. In 20 mutants, the TnphoA'-1 lacZ gene was expressed at a low basal level. These mutants had insertions in the opposite orientation. All 43 phn::TnphoA'-1 insertions were recombined onto the chromosome to test for mutational effects, and their structures on the chromosome were verified by DNA hybridization. Those in the + orientation were switched to TnphoA'-9, which has an outward promoter for expression of downstream genes. These insertions were tested for polar effects by measuring beta-glucuronidase synthesis from a uidA gene transcriptionally fused to the 3' end of the phnP gene. The results indicate the following: (i) the phnC-to-phnP gene cluster is an operon of 14 genes, and the phnC promoter is the sole psi promoter; (ii) three gene products (PhnC, PhnD, and PhnE) probably constitute a binding protein-dependent Pn transporter; (iii) seven gene products (PhnG, PhnH, PhnI, PhnJ, PhnK, PhnL, and PhnM) are required for catalysis and are likely to constitute a membrane-associated carbon-phosphorus (C-P) lyase; (iv) two gene products (PhnN and PhnP) are not absolutely required and may therefore be accessory proteins for the C-P lyase; and (v) two gene products (PhnF and PhnO) are not required for Pn use and may have a regulatory role because they have sequence similarities to regulatory proteins. The mechanism for breaking the C-P bond by a lyase is discussed in light of these results.
A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy (2009)

Our new algorithm is significantly more accurate than the Hans' algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials.
IMPROVING THE SECURITY OF YOUR UNIX SYSTEM (1990)

This document describes the security features provided by the operating system, and how UNIX S O f they should be used. The discussion centers around version 4.x of Sun , the version o sold by Sun Microsystems. Most of the information presented applies equally well UNIX UNIX to other systems. Although there is no way to make a computer completely secure e i against unauthorized use (other than to lock it in a room and turn it off), by following th nstructions in this document you can make your system impregnable to the &amp;quot;casual&amp;quot; sys-
Lessons from computer simulations of ablation of atrial fibrillation (2016)

This paper reviews the simulations of catheter ablation in computer models of the atria, from the first attempts to the most recent anatomical models. It describes how postulated substrates of atrial fibrillation can be incorporated into mathematical models, how modelling studies can be designed to test ablation strategies, what their current trade-offs and limitations are, and what clinically relevant lessons can be learnt from these simulations. Drawing a parallel between clinical and modelling studies, six ablation targets are considered: pulmonary vein isolation, linear ablation, ectopic foci, complex fractionated atrial electrogram, rotors and ganglionated plexi. The examples presented for each ablation target illustrate a major advantage of computer models, the ability to identify why a therapy is successful or not in a given atrial fibrillation substrate. The integration of pathophysiological data to create detailed models of arrhythmogenic substrates is expected to solidify the understanding of ablation mechanisms and to provide theoretical arguments supporting substrate-specific ablation strategies.
Expression level of a transgenic λ2 chain results in isotype exclusion and commitment to B1 cells (1998)

Two new lambda2 chain-transgenic mouse lines were established, both of which showed stable transgene expression during aging of the mice. The line L23, which expressed the transgene at low levels, exhibited normal B cell development, antibody responses and serum Ig levels. Most of the B cells in this mouse line co-expressed the transgenic lambda2 chain together with an endogenous kappa chain, thus showing poor allelic exclusion of endogenous L chains. On the other hand, high expression of the transgenic lambda2 chain in the other mouse line, L2, resulted in nearly complete exclusion of endogenous L chain isotypes. In this line, the lambda2 transgene was already detectable in the cytoplasm of all preB-II cells and some pro/preB-I cells. Its expression during these early phases obviously inhibited development of conventional B2 cells, since the B cells in the periphery of these mice were almost exclusively of the B1 type. This finding was confirmed by adoptive transfer of transgenic bone marrow into lethally irradiated recipients. Very few B cells were present in the spleen of such recipients. The serum IgM levels of L2 mice were close to normal and the majority of these IgM were associated with the transgenic lambda2 chain. Antibody responses to thymus-dependent antigens in such mice were almost exclusively found to be of IgM class. Together, these findings indicate a developmental bias leading to a predominance of B1 cells in the L2 line.
Managing Leakage Energy in Cache Hierarchies (2003)

Energy management is important for a spectrum of systems ranging from high-performance architectures to low-end mobile and embedded devices. With the increasing number of transistors, smaller feature sizes, lower supply and threshold voltages, the focus on energy optimization is shifting from dynamic to leakage energy. In fact, leakage energy is projected to become the dominant portion of the chip power budget for 0.10 micron technology and below. Leakage energy is of particular concern in dense cache memories that form a major portion of the transistor budget.
Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study (2012)

This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m(2) (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704.
Wireless Systems and Technologies: An Overview (1993)

The wondrous inventions of Marconi brought about the first wireless revolution, which dramatically transformed the ways people worked and played. The telecommunications industry is now in the midst of a second wireless revolution, which is projected to have an impact as large as that of the original. The current revolution began with the invention of cellular communications technology. As new discoveries were made and cellular technology advanced, another generation of wireless applications has emerged during the past decade. Recent developments, including AT&T's proposed $12.6 billion merger with McCaw Cellular Communications Inc., whose network now spans nearly one-third of the United States, provide overwhelming proof of the tremendous potential of these technologies. Future applications will make it easier than ever for people to avail themselves of anywhere, anytime voice, data, and messaging services through the telecommunications network. This paper discusses the development of current cellular applications and technologies, and also explores the expanding wireless telecommunications network of the future.
Comparison of the immunosuppressive effects of asparaginases from Escherichia coli and Vibrio succinogenes. (1980)

Abstract The immunosuppressive effects of antileukemic asparaginases isolated from Escherichia coli and Erwinia carotovora are well documented, but the basis for the immunosuppression is unclear. In addition to catalyzing the deamination of l-asparagine, the E. coli and E. carotovora enzymes also deaminate l-glutamine (glutaminase activity). Many investigators have suggested that this glutaminase activity may be the cause of immunosuppression. The role of glutaminase activity in this immunosuppression has been difficult to evaluate, largely because the lack of a glutaminase-free asparaginase obtainable in significant quantity has precluded any rigorous in vivo experimentation. This laboratory has isolated an asparaginase from Vibrio succinogenes which has potent antilymphoma activity and lacks glutaminase activity. In the present communication, we report the effects of treatment with E. coli and V. succinogenes asparaginases on specialized immune responses in BALB/cCrgl mice. The immunosuppressive effects of E. coli and V. succinogenes asparaginase on the humoral response of mice during sheep red blood cell (SRBC) immunization were investigated using the plaque-forming cell assay. There was a marked reduction in the number of IgM and IgG plaque-forming cells in the E. coli asparaginase-treated group. No reduction in the plaque-forming cell response was observed in the V. succinogenes asparaginase-treated mice. Levels of antibody against SRBC as determined by hemagglutination were also depressed in E. coli asparaginase-treated mice. Splenocytes isolated from mice immunized with SRBC and simultaneously treated with asparaginase were tested for their capability to serve as effector cells in a direct-target killing assay using 51Cr-labeled SRBC9s. At all concentrations tested, the E. coli enzyme significantly suppressed the cytotoxic response of splenocytes, while splenocytes from mice treated with V. succinogenes asparaginase maintained control levels of cytotoxicity. The data provide evidence that a glutaminase-free asparaginase from V. succinogenes does not suppress the in vivo immune response of mice to SRBC as compared to the pronounced immunosuppressive effects observed in mice treated with E. coli asparaginase.
Aristoforin, a Novel Stable Derivative of Hyperforin, Is a Potent Anticancer Agent (2004)

Hyperforin, a natural product of St. John's wort (Hypericum perforatum L.), has a number of pharmacological activities, including antidepressive and antibacterial properties. Furthermore, hyperforin has pronounced antitumor properties against different tumor cell lines, both in vitro and in vivo. Despite being a promising novel anticancer agent, the poor solubility and stability of hyperforin in aqueous solution limits its potential clinical application. In this study, we present the synthesis of hyperforin derivatives with improved pharmacological activity. The synthesized compounds were tested for their solubility and stability properties. They were also investigated for their antitumor properties, both in vitro and in vivo. One of these hyperforin derivatives, Aristoforin, is more soluble in aqueous solution than hyperforin and is additionally highly stable. Importantly, it retains the antitumor properties of the parental compound without inducing toxicity in experimental animals. These data strongly suggest that Aristoforin has potential as an anticancer drug.
Application of a clustering adaptive fuzzy logic controller in a brushless DC drive (2002)

A clustering adaptive fuzzy logic system (CAFLS) is proposed as a high performance controller in a brushless DC (BLDC) motor drive. Objectives of the proposed system include elimination of speed ripple due to cogging at low speeds under heavy load as well as good dynamic response. The CAFLS implemented has the advantages of computational simplicity and self-tuning characteristics.
Targeting mutated protein tyrosine kinases and their signaling pathways in hematologic malignancies. (2005)

Over the last decade, major advances have been made in the elucidation of mechanisms involved in leukemogenesis, and this is particularly true with regard to deregulated protein tyrosine kinase (PTK) activation. This progress had led to the development of small molecules that specifically inhibit the abnormally activated kinase. The first example of such targeted therapy is imatinib-mesylate, an inhibitor of the BCR-ABL fusion gene that is found in more than 90% of patients with Philadelphia positive (Ph+) chronic myeloid leukemia (CML) and in 20-30% of those with Ph+ acute lymphoblastic leukemia (ALL). The excellent clinical results obtained with imatinib in CML have completely changed the therapeutic approach to this disease, and imatinib is now the gold standard for treatment of newly diagnosed CML. This has instigated a tremendous effort to develop targeted PTK therapy based on the presence of over 40 chromosomal translocations that lead to deregulation of 12 different PTK associated with various hematologic malignancies. That deregulated PTK are also involved in the pathogenesis of acute leukemia is underlined by the frequent occurrence of mutations leading to constitutive activation of the FLT3. Experimental as well as clinical evidence supports a model of acute leukemia based on the co-operation of constitutive active PTK with mutations of transcriptional regulators. Here we review the general impact of mutated PTK on the pathogenesis of various hematologic malignancies. We also discuss the development of new targeted therapies and strategies to circumvent the increasing problems related to the emergence of drug resistance by targeting downstream signaling mediators that are essential for transformation by deregulated PTK.
Intestinal Immune Response to HumanCryptosporidiumsp. Infection (2007)

Cryptosporidium is an obligate intracellular protozoan parasite that is a major cause of diarrheal illness worldwide. Cryptosporidium primarily infects the distal small intestine. Immunocompetent hosts control and eliminate the infection, which typically causes acute, self-limited watery diarrhea lasting 5 to 10 days. However, in patients with defects in cellular immune responses (e.g., AIDS, malnutrition, or defects in the CD40-CD154 system), Cryptosporidium frequently causes persistent or chronic diarrhea and may also involve the biliary tract (40). In malnourished children, persistent diarrhea is associated with increased susceptibility to recurrent diarrheal episodes, which can lead to death or chronic nutritional and cognitive sequelae (1, 9, 33). Thus, the host immune response plays a critical role in the control of human cryptosporidiosis.

Although extensive studies with various animal models have provided important insight into the host immune response towards Cryptosporidium parvum, the ability of these models to explain the human immune response is limited. The clinical picture in rodents differs from that in humans, as mice do not get diarrhea after infection. Nonhuman primates, although probably the best in vivo model to mimic human disease, are difficult to work with, expensive, and not widely available. Cryptosporidium hominis, the pathogen causing most human cryptosporidiosis, infects only humans and gnotobiotic pigs, thus limiting data from animal models. Most importantly, comparison of animal and human data has shown that the immune response towards Cryptosporidium in humans differs significantly from that in animals; for example, in mice gamma interferon (IFN-γ) production seems to be associated with the innate and primary immune responses (35, 47), whereas in humans it is most probably associated with the memory response towards the parasite (93). Conducting studies to elucidate human mucosal immune responses is difficult. Patients with a natural infection would be the ideal subjects to study, but it is difficult to identify cases. Healthy human volunteers can be studied, but they typically experience a milder illness than malnourished children and AIDS patients. Human intestinal tissue samples can be obtained only by invasive procedures, limiting the numbers of subjects and samples available. Some data can be obtained from in vitro infections, but most of the target cells are immortalized and may not be ideal for studying mechanisms involving apoptosis. Furthermore, the immune cells in the peripheral blood may exhibit properties different from the properties of cells found in the intestinal compartment. Thus, knowledge about the human immune response towards Cryptosporidium infection is far from complete. Still, important recent advances have been made. The goal of this paper is to review the current literature to provide an understanding of the human immune response towards the parasite. We include some relevant data from other models only when the data shed light on studies performed with human cells or tissues.
[Molecular biology of pancreatic cancer: overexpression of fibroblast growth factors]. (1994)

In the present study, the expression of a acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 were analyzed in 60 pancreatic cancer samples using Northern blot analysis, immunoblotting, in situ hybridization and immunohistochemical techniques. aFGF, bFGF and FGFR-1 were present in 63%, 55% and 52% of the tumor samples, respectively. Twenty-seven of the 60 pancreatic cancer tissue samples exhibited coexpression of aFGF and bFGF. In contrast, 14 of the tumor samples did not show immunoreactivity for aFGF or bFGF in the tumor cells. The expression of aFGF in the tumor cells had no influence on the postoperative survival period, whereas patients whose tumors were positive for bFGF and/or FGF-receptor-1 had significantly shorter postoperative survival periods. Our results suggest that bFGF and FGFR-1 may play a role in the growth behavior of pancreatic cancer and may contribute to tumor aggressiveness.
Scaling behavior of the elastic properties of colloidal gels (1990)

The scaling behavior of the elastic properties of colloidal gels that are well above the gelation threshold is studied both theoretically and experimentally. A scaling theory was developed by considering the structure of the gel network as a collection of flocs, which are fractal objects closely packed throughout the sample. Two regimes are found based on the relative value of the elastic constant of the interfloc links to that of the flocs. In the strong-link (interfloc) regime, the elastic constant of the gels increases but the limit of linearity decreases with increasing particle concentration, whereas in the weak-link regime both the elastic constant and the limit of linearity increase with increasing particle concentration. Rheological studies on the elastic behavior of two types of boehmite alumina gels, Catapal and Dispal powders, were performed. Both types of gels in the concentration range studied showed the strong-link behavior and the results are in good agreement with the theoretical predictions. The value of the fractal dimension of the flocs D\ensuremath{\simeq}1.95, deduced from the rheological measurements, is in agreement with the value D\ensuremath{\simeq}2.04 deduced from the static light-scattering measurements on dilute suspensions. Therefore the scaling theory we developed also enables us to extract structural information from the rheological measurements.
PCR-Based Method To Differentiate the Subspecies of the Mycobacterium tuberculosis Complex on the Basis of Genomic Deletions (2003)

The classical Mycobacterium tuberculosis complex (MtbC) subspecies include Mycobacterium tuberculosis, Mycobacterium africanum (subtypes I and II), Mycobacterium bovis (along with the attenuated M. bovis bacillus Calmette-Guérin [BCG]), and Mycobacterium microti; increasingly recognized MtbC groupings include Mycobacterium bovis subsp. caprae and "Mycobacterium tuberculosis subsp. canettii." Previous investigations have documented each MtbC subspecies as a source of animal and/or human tuberculosis. However, study of these organisms is hindered by the lack of a single protocol that quickly and easily differentiates all of the MtbC groupings. Towards this end we have developed a rapid, simple, and reliable PCR-based MtbC typing method that makes use of MtbC chromosomal region-of-difference deletion loci. Here, seven primer pairs (which amplify within the loci 16S rRNA, Rv0577, IS1561', Rv1510, Rv1970, Rv3877/8, and Rv3120) were run in separate but simultaneous reactions. Each primer pair either specifically amplified a DNA fragment of a unique size or failed, depending upon the source mycobacterial DNA. The pattern of amplification products from all of the reactions, visualized by agarose gel electrophoresis, allowed immediate identification either as MtbC composed of M. tuberculosis (or M. africanum subtype II), M. africanum subtype I, M. bovis, M. bovis BCG, M. caprae, M. microti, or "M. canettii" or as a Mycobacterium other than MtbC (MOTT). This MtbC PCR typing panel provides an advanced approach to determine the subspecies of MtbC isolates and to differentiate them from clinically important MOTT species. It has proven beneficial in the management of Mycobacterium collections and may be applied for practical clinical and epidemiological use.
Processor Control Flow Monitoring Using Signatured Instruction Streams (1987)

This paper presents an innovative approach, called signatured instruction streams (SIS), to the on-line detection of control flow errors caused by transient and intermittent faults. At compile time an application program is appropriately partitioned into smaller subprograms, and cyclic codes, or signatures, characterizing the control flow of each subprogram are generated and embedded in the object code. At runtime, special built-in hardware regenerates these signatures using runtime information and compares them to the precomputed signatures. A mismatch indicates the detection of an error. A demonstration system, based on the MC68000 processor, has been designed and built. Fault insertion experiments have been performed using the demonstration system. The demonstration system, using 17 percent hardware overhead, is able to detect 98 percent of faults affecting the control flow and 82 percent of all randomly inserted faults.