gebhart/patrepeval huggingface dataset:
Characteristics of Escherichia coli Sequence Type 131 Isolates That Produce Extended-Spectrum β-Lactamases: Global Distribution of the H 30-Rx Sublineage (2014)

We designed a study to describe the characteristics of sequence type 131 (ST131) lineages, including the H30-Rx sublineage, among a global collection of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates from 9 countries collected from 2000 to 2011. A total of 240 nonrepeat isolates from Canada, the United States, Brazil, the Netherlands, France, the United Arab Emirates (UAE), India, South Africa, and New Zealand were included. Established PCR, sequencing, and typing methods were used to define ST131 lineages, H30 and H30-Rx phylogenetic groups, gyrA and parC mutations, virotypes, and plasmid-mediated quinolone resistance determinants. The majority of the isolates produced CTX-M-15 with aac(6')-lb-cr, belonged to phylogenetic group B2, and were positive for the H30 lineage with the gyrA1AB and parC1aAB mutations. ST131 showed 15 distinct pulsotypes; 43% of the isolates belonged to four pulsotypes, with a global distribution. Seventy-five percent of the ST131 isolates belonged to H30-Rx; this sublineage was present in all the countries and was associated with multidrug resistance, blaCTX-M-15, aac(6')-lb-cr, and virotypes A and C. The H41 lineage was negative for the ST131 pabB allele-specific PCR. The multidrug-resistant H30-Rx sublineage poses an important public health threat due to its global distribution, association with virotype C, and high prevalence among ST131 isolates that produce CTX-M-15.
Markers of Inflammation and Cardiovascular Disease (2003)

In 1998, the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention. Among the strategies discussed was the measurement of markers of inflammation.1 The Conference concluded that “many of these markers (including inflammatory markers) are not yet considered applicable for routine risk assessment because of: (1) lack of measurement standardization, (2) lack of consistency in epidemiological findings from prospective studies with endpoints, and (3) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors.” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using standard risk factors. Since these publications, a large number of peer-reviewed scientific reports have been published relating inflammatory markers to cardiovascular disease (CVD). Several commercial assays for inflammatory markers have become available. As a consequence of the expanding research base and availability of assays, the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly. Despite this, there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice.

On March 14 and 15, 2002, a workshop titled “CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease: Applications to Clinical and Public Health Practice” was convened in Atlanta, Ga, to address these issues. The goals of this workshop were to determine which of the currently available tests should be used; what results should be used to define high risk; which patients should be tested; and the indications for which the tests would be most useful. These …
Helper Dependent Adenovirus Vectors: Progress and Future Prospects (2013)

Sixteen years after Graham and coworkers described the most used system for generating helper-dependent adenovirus (HDAd) vectors, production systems have evolved considerably, and most resulting preparations have titres of 1 × 10(13) IU/ml (infection units/ml) and very low helper contamination levels (<0.1%). These advances in production, as well as the attractive characteristics of these vectors (large insert capacity and low cell immune response compared with first-generation Ad vectors) make them very interesting for many research purposes as they have become more accessible to the scientific community. In this review we summarise the latest strategies for producing HDAd vectors, describe the main areas of interest for which HDAd vectors are being used, and comment on the future prospects for HDAd vectors in gene therapy.
Glioblastoma and stem cells. (2008)

This review presents compelling evidence that human glioblastoma is a heterogenous tumor composed from tumor cells and small portion of cancer stem cells -- tumor-initiating cells, which have a high tumorigenic potential and a low proliferation rate. Glioma cancer stem cells are phenotypically similar to the normal stem cells, they express CD133 gene and other genes characteristic of neural stem cells and posses the self-renewal potential. Cancer stem cells derived from glioblastoma are capable recapitulate original polyclonal tumors when xenografted to nude mice. They are chemoresistant and radioresistant and therefore responsible for tumor progression and recurrence after conventional glioblastoma therapy. Cancer stem cells contribute to glioma radioresistance by an increase of DNA repair capacity through preferential activation of the DNA damage response checkpoints. Potential therapies that modulate or target cancer stem cells are also reviewed. Mesenchymal stem cells and/or neural stem cells were shown to target brain tumors therefore these cells are considered as an effective delivery system to target and disseminate therapeutic agents to brain tumors. Stem cell-based gene therapies for glioblastoma were shown in experiments to be effective way to target brain tumors. Effects of bone morphogenetic protein (BMP4) on glioma cancer stem cells are also reviewed. BMP4 reduces effectively proliferation of CD133 positive cells in vitro and the tumor growth in vivo. BMP4 may act as a key inhibitory regulator of cancer initiation and therefore may be used in combined stem cell-based therapy as a non-cytotoxic therapeutic agent.
A silicon-on-insulator circuit for high-temperature, high-voltage applications (2002)

The authors previously proposed the concept of a composite high-voltage device using series-connected low-voltage SOI (silicon-on-insulator) MOSFETs. In the present work, they demonstrate how the composite device can circumvent the fundamental materials limitations of bulk devices for high-voltage, high-temperature applications. Experimental circuits were fabricated on SIMOX (separation by implanted oxygen) substrates using an SOI NMOS process. For the purpose of demonstrations, external resistors were used as the bias elements. Individual transistor breakdown voltages were about 6-7 V, and did not vary significantly from 24 degrees C to 400 degrees C. The composite device characteristics closely resemble those of the individual MOSFETs. In particular, the breakdown voltage (typically 26-30 V) is nearly constant over the temperature range studied. Drain characteristics of a typical five-transistor composite device are shown for several stage temperatures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Prevention of Diabetes in NOD Mice by Injection of Autoreactive T-Lymphocytes (1989)

The nonobese diabetic (NOD) mouse develops a high incidence of autoimmune diabetes and is believed to be a good model for insulin-dependent diabetes mellitus (IDDM) in humans. We isolated T-lymphocyte lines from islets of newly diabetic NOD mice, some of which are autoreactive to NOD spleen cells. Because autoreactive T-lymphocytes have been implicated in immune suppression, we injected NOD mice with an autoreactive T-lymphocyte line. The injected mice had a marked decrease in incidence of IDDM compared with control mice. Moreover, their islets showed no insulitis at 1 yr of age. We conclude that autoreactive T-lymphocytes can prevent the development of IDDM in NOD mice. This result suggests that 1) islets contain both effector cells capable of damaging pancreatic beta-cells and cells able to regulate this autoimmune response, and 2) development of IDDM depends on the balance between these opposing forces.
7-endo Selective Aryl Radical Cyclization onto Enamides Leading to 3-Benzazepines:  Concise Construction of a Cephalotaxine Skeleton (2005)

Bu3SnH-mediated radical cyclizations of 2-(2-bromophenyl)-N-ethenylacetamide gave 6-exo cyclization product 15 as the major product, whereas N-[2-(2-bromophenyl)ethyl]-N-ethenylamides gave almost exclusively 7-endo cyclization products. These results indicated that the position of the carbonyl group on enamide played an important role in deciding the course of the cyclization. The 7-endo selective cyclization was applied to concise construction of a cephalotaxine skeleton.
Effective tumor treatment targeting a melanoma/melanocyte-associated antigen triggers severe ocular autoimmunity (2008)

Nonmutated tissue differentiation antigens expressed by tumors are attractive targets for cancer immunotherapy, but the consequences of a highly effective antitumor immune response on self-tissue have not been fully characterized. We found that the infusion of ex vivo expanded adoptively transferred melanoma/melanocyte-specific CD8+ T cells that mediated robust tumor killing also induced autoimmune destruction of melanocytes in the eye. This severe autoimmunity was associated with the up-regulation of MHC class I molecules in the eye and high levels of IFN-gamma derived from both adoptively transferred CD8+ T cells and host cells. Furthermore, ocular autoimmunity required the presence of the IFN-gamma receptor on target tissues. Data compiled from >200 eyes and tumors in 10 independently performed experiments revealed a highly significant correlation (P < 0.0001) between the efficacy of tumor immunotherapy and the severity of ocular autoimmunity. Administration of high doses of steroids locally mitigated ocular autoimmunity without impairing the antitumor effect. These findings have particular importance for immunotherapies directed against self-antigens and highlight the need for targeting unique tumor antigens not expressed in critical tissues.
Effects of anticancer drugs on the metabolism of the anticancer drug 5,6‐dimethylxanthenone‐4‐acetic (DMXAA) by human liver microsomes (2001)

These results indicate that alteration of the pharmacokinetics of DMXAA appears unlikely when used in combination with other common anticancer drugs. However, this does not rule out the possibility of pharmacokinetic interactions with other drugs used concurrently with this combination of anticancer drugs.
Investigations on the origin of tobacco-specific nitrosamines n mainstream smoke of cigarettes (1990)

The origin of tobacco-specific nitrosamines (TSNA) in mainstream smoke and the possible contribution of synthesis during the smoking procedure was investigated. Addition of the nitrosamine precursors nitrate and nicotine to the tobacco prior to smoking did not change the mainstream smoke concentrations of N'-nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), whereas the mainstream smoke concentration of N'-nitrosoanabasine (NAB) and N'-nitrosoanatabine (NAT) increased after spiking the cigarettes with nitrate. Data for TSNA in tobacco and in mainstream smoke and for nitrate in tobacco of commercial cigarettes of the West German market, taken from previous investigations, were used to calculate the mainstream smoke/tobacco ratios for NNN and NNK. These ratios were corrected for ventilation and cigarette length. It is shown that the ratios are constant and neither depend on the nicotine level nor on the nitrate level of the tobacco except for NNK in the nitrate rich dark tobacco type cigarettes. For nonfilter cigarettes the transfer rates of NNN and NNK which had been corrected for ventilation and cigarette length amounted to 23 or 34% respectively. For filter cigarettes a transfer rate of 13% for NNN and 23% for NNK was calculated. Furthermore it is shown that the mainstream smoke/tobacco ratios for NNN and NNK are constant over the whole length of the cigarettes except for NNK in dark tobacco type cigarettes. The results of this investigation indicate that pyrosynthesis of NNN does not occur and that it is very unlikely for NNK at least for lower nitrate levels. Thus with few exceptions the TSNA burden of smokers is predominantly influenced by the amount of preformed NNN and NNK in tobacco.
Bayesian learning in undirected graphical models: approximate MCMC algorithms (2004)

Bayesian learning in undirected graphical models---computing posterior distributions over parameters and predictive quantities---is exceptionally difficult. We conjecture that for general undirected models, there are no tractable MCMC (Markov Chain Monte Carlo) schemes giving the correct equilibrium distribution over parameters. While this intractability, due to the partition function, is familiar to those performing parameter optimisation, Bayesian learning of posterior distributions over undirected model parameters has been unexplored and poses novel challenges. We propose several approximate MCMC schemes and test on fully observed binary models (Boltzmann machines) for a small coronary heart disease data set and larger artificial systems. While approximations must perform well on the model, their interaction with the sampling scheme is also important. Samplers based on variational mean-field approximations generally performed poorly, more advanced methods using loopy propagation, brief sampling and stochastic dynamics lead to acceptable parameter posteriors. Finally, we demonstrate these techniques on a Markov random field with hidden variables.
Posthatch Incubation Time and Early Growth of Broiler Chickens (1983)

Fertile eggs from broiler breeder hens were hatched to evaluate the effects of time of hatch and time held in the incubator posthatch on subsequent chick weights to 4 weeks of age. All chicks suitable for removal at 486, 492, 498, 504, 510, 516, and 522 hr of incubation in Trial 1 were weighed at their respective hatch times. One-half of each group remained in the incubator until 522 hr and the rest were placed in brooding pens at the initial weighing time, with water provided immediately and feed 6 hr later. The earlier the chicks hatched, the greater was the weight loss when held in the incubator to 522 hr (over 10% loss for those hatched at 486 and 492 hr). Males removed at hatch times of 486, 492, 498, and 504 hr were significantly heavier to 4 weeks of age than were their hatch mates held to 522 hr. A similar but less pronounced response was noted for females. Time on feed did not account for the total differences noted. Earlier hatching female chicks in Trial 1 were heavier at the time of hatch. They tended to maintain this weight advantage to 4 weeks of age when not held, but lost it when left in the incubator for the total hatching period. This effect was less pronounced for males. Trial 2 eggs were obtained from a different breeding source that had a larger egg size. Resulting chick weights were a higher percentage of initial egg weight than those in Trial 1. With hatch times of 492, 500, 508, and 516 hr, the trend was similar to that in Trial 1 but much less pronounced.
Nonlinear optical transitions of GaAs∕AlGaAs asymmetric double-well structures (2006)

A thin AlGaAs barrier (2.5nm) inserted into a GaAs∕AlGaAs single heterojunction formed a square and a wedge-shaped triangular quantum well in the conduction band. In such a structure, the valence band does not have tunnel-coupled energy levels. Hence, the photogenerated valence holes tend to move to the GaAs flatband region. This asymmetric quantum structure showed intense nonlinear photoluminescence emission behavior with external excitation power and magnetic field. Increasing the external laser power simply caused the number of photogenerated holes to increase near the interface close to the quantum well, which then recombined with the conduction band electrons. External magnetic fields resulted in an increased Coulomb attraction which generated dynamic movement of valence holes. The migration of unbound holes to the interface region from the GaAs flatband area produced highly nonlinear optical transitions in magnetic fields.
Regulation and Activities of α-Fetoprotein (1997)

alpha-Fetoprotein (AFP) is one of the major serum proteins in the early life of mammals. The function of this protein is not yet fully understood. AFP is an oncodevelopmental gene product which is expressed at high levels in the embryonic yolk sac and fetal liver. The synthesis of AFP decreases dramatically after birth. Only trace amounts of AFP are synthesized in the adult liver. However, expression of the AFP gene is reactivated in the adult during liver regeneration and hepatocarcinogenesis. AFP is an excellent model system for studying the temporal and tissue-specific regulation of oncodevelopmental gene expression. Experiments with transgenic mice and DNA transfection studies have revealed several transcriptional control regions and cis-acting elements in the AFP gene. A large number of trans-acting protein factors interacting with these cis-acting elements have also been identified. Recent studies demonstrated that expression of AFP is regulated by at least two major signal transduction pathways in response to extracellular stimuli. The interactions between steroid hormone receptors and transcriptional factors which respond to separate signal transduction pathways result in transcriptional regulation of AFP gene expression. Trans-acting protein factors or steroid receptors complexed with given response elements can display different activities in different cell types due to cross-talk among both local protein-protein interactions within the DNA-binding domain, and distal protein-protein interactions. However, the detailed mechanisms of AFP gene expression are still not completely understood.
Symbolic model checking for sequential circuit verification (1994)

The temporal logic model checking algorithm of Clarke, Emerson, and Sistla (1986) is modified to represent state graphs using binary decision diagrams (BDD's) and partitioned transition relations. Because this representation captures some of the regularity in the state space of circuits with data path logic, we are able to verify circuits with an extremely large number of states. We demonstrate this new technique on a synchronous pipelined design with approximately 5/spl times/10/sup 120/ states. Our model checking algorithm handles full CTL with fairness constraints. Consequently, we are able to express a number of important liveness and fairness properties, which would otherwise not be expressible in CTL. We give empirical results on the performance of the algorithm applied to both synchronous and asynchronous circuits with data path logic.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Organometallic Reactions in Aqueous Media. Indium- and Zinc-Mediated Allylation of Sulfonimines1 (2000)

Sulfonimines derived from aryl and nonenolizable aliphatic aldehydes can be effectively allylated to the corresponding homoallylic sulfonamides with allylic bromides promoted by indium or zinc. The solvent used can be water, THF, or a mixed aqueous THF solvent. The regioselectivity and stereoselectivity of the reaction were studied.
Betulinic Acid Derivatives:  A New Class of Human Immunodeficiency Virus Type 1 Specific Inhibitors with a New Mode of Action (1996)

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.
Directed evolution can rapidly improve the activity of chimeric assembly-line enzymes (2007)

Nonribosomal peptides (NRPs) are produced by NRP synthetase (NRPS) enzymes that function as molecular assembly lines. The modular architecture of NRPSs suggests that a domain responsible for activating a building block could be replaced with a domain from a foreign NRPS to create a chimeric assembly line that produces a new variant of a natural NRP. However, such chimeric NRPS modules are often heavily impaired, impeding efforts to create novel NRP variants by swapping domains from different modules or organisms. Here we show that impaired chimeric NRPSs can be functionally restored by directed evolution. Using rounds of mutagenesis coupled with in vivo screens for NRP production, we rapidly isolated variants of two different chimeric NRPSs with approximately 10-fold improvements in enzyme activity and product yield, including one that produces new derivatives of the potent NRP/polyketide antibiotic andrimid. Because functional restoration in these examples required only modest library sizes (10(3) to 10(4) clones) and three or fewer rounds of screening, our approach may be widely applicable even for NRPSs from genetically challenging hosts.
The Tango: A Tangible Tangoreceptive Whole-Hand Human Interface (2005)

We describe the Tango, a new passive haptic interface for whole-hand interaction with 3D objects. The Tango is shaped like a ball and can be grasped comfortably in one hand. Its pressure sensitive skin measures the contact pressures exerted by the user's hand, and accelerometers within the device measure its motion and attitude. This information can be used for novel modes of interaction with three-dimensional objects. We describe the design of the device, and the software for interpreting the sensor data for user interaction. Accompanying this paper, there is a demonstration of the device at the Hands-On Demo session of the conference.
Regulation of calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1): Review (2006)

The response of living cells to change in cell environment depends on the action of second messenger molecules. The two second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in the complex interaction between cAMP and Ca2+ second messenger systems. Some PDE1 isozymes have similar kinetic and immunological properties but are differentially regulated by Ca2+ and calmodulin. Accumulating evidence suggests that the activity of PDE1 is selectively regulated by cross-talk between Ca2+ and cAMP signalling pathways. These isozymes are also further distinguished by various pharmacological agents. We have demonstrated a potentially novel regulation of PDE1 by calpain. This study suggests that limited proteolysis by calpain could be an alternative mechanism for the activation of PDE1. We have also shown PDE1 activity, expression and effect of calpain in the rat model in vitro of cardiac ischemia-reperfusion.