gebhart/patrepeval huggingface dataset:
Susceptibility of porcine endogenous retrovirus to anti‐retroviral inhibitors (2016)

The study results indicate that some of the licensed anti-retroviral drugs may be useful for controlling PERV infection. However, the efficacy at nanomolar concentrations put forward integrase inhibitors as a drug that has the potential to be useful in the event that xenotransplantation recipients have evidence of PERV transmission and replication.
Therapy-related myeloid leukemia. A model for leukemogenesis (2009)

Therapy-related acute myeloid leukemia (t-AML) is a distinctive clinical syndrome occurring after exposure to chemotherapy or radiotherapy. t-AML arises in most cases from a multipotential hematopoietic stem cell or, less commonly, in a lineage committed progenitor cell. The prognosis for patients with t-AML is poor, as current forms of therapy are largely ineffective. Molecular analysis and gene expression profiling analysis of t-AML has revealed that there are distinct subtypes of t-AML that have a characteristic gene expression pattern. Establishing the molecular pathways involved in t-AML may facilitate the identification of selectively expressed genes that can be exploited for the development of urgently-needed targeted therapies.
Identification and Characterization of Heparin Binding Regions of the Fim2 Subunit ofBordetella pertussis (1998)

Bordetella pertussis fimbriae bind to sulfated sugars such as heparin through the major subunit Fim2. The Fim2 subunit contains two regions, designated H1 and H2, which show sequence similarity with heparin binding regions of fibronectin, and the role of these regions in heparin binding was investigated with maltose binding protein (MBP)-Fim2 fusion proteins. Deletion derivatives of MBP-Fim2 showed that both regions are important for binding to heparin. The role of H2 in heparin binding was confirmed by site-directed mutagenesis in which basic amino acids were replaced by alanine. These studies revealed that Lys-186 and Lys-187 are important for heparin binding of MBP-Fim2, whereas Arg-179 is not required. Peptides derived from H1 and H2 (pepH1 and pepH2) also showed heparin binding activity. Using a series of peptides, in each of which a different basic amino acid was substituted for alanine, we demonstrated that the structural requirements for heparin binding differ significantly among pepH1 and pepH2 peptides. A Pepscan analysis of Fim2 revealed regions outside H1 and H2 which bind heparin and showed that not only basic amino acids but also tyrosines may be important for binding to sulfated sugars. A comparison of the heparin binding regions of Fim2 with homologous regions of Fim3 and FimX, two closely related but antigenically distinct fimbrial subunits, showed that basic amino acids and tyrosines are generally conserved. The major heparin binding regions identified in Fim2 are part of epitopes recognized by human antibodies, suggesting that the heparin binding regions are exposed at the fimbrial surface and are immunodominant. Since B. pertussis fimbriae show weak serological cross-reactivity, the differences in primary structure in the heparin binding regions of Fim2, Fim3, and FimX may affect antibody binding but not heparin binding, allowing the bacteria to evade antibody-mediated immunity by switching the fimbrial gene expressed.
Development of a Practical Synthesis of STA-5312, a Novel Indolizine Oxalylamide Microtubule Inhibitor (2007)

An efficient synthesis of the novel microtubule inhibitor STA-5312 (3-[(4-cyanophenyl)methyl]-N-(3-methyl-5-isothiazolyl)-α-oxo-1-indolizineacetamide) was developed. A novel DMF/Me2SO4 directed regioselective synthesis of the 3-(4-cyanobenzoyl)-indolizine (4) was a critical transformation within the four-step process. Alternatively, a CuCl mediated synthesis of 3-(4-cyanobenzyl)indolizine (5) was also developed. All intermediates were obtained in high quality and were used directly for the next step without extensive purification. The drug substance itself was purified by recrystallization from a mixture of THF and water, resulting in a high purity product (HPLC >98%). The process was applied successfully in the manufacturing of kilograms of GMP API.
Modulation of GABAA Receptor Function by Nonhalogenated Alkane Anesthetics: The Effects on Agonist Enhancement, Direct Activation, and Inhibition (2003)

At clinically relevant concentrations, ethers, alcohols, and halogenated alkanes enhance agonist action on the γ-aminobutyric acidA (GABAA) receptor, whereas nonhalogenated alkanes do not. Many anesthetics also directly activate and/or inhibit GABAA receptors, actions that may produce important behavioral effects; although, the effects of nonhalogenated alkane anesthetics on GABAA receptor direct activation and inhibition have not been studied. In this study, we assessed the abilities of two representative nonhalogenated alkanes, cyclopropane and butane, to enhance agonist action, directly activate, and inhibit currents mediated by expressed α1β2γ2L GABAA receptors using electrophysiological techniques. Our studies reveal that cyclopro- pane and butane enhance agonist action on the GABAA receptor at concentrations that exceed those required to produce anesthesia. Neither nonhalogenated alkane directly activated nor inhibited GABAA receptors, even at concentrations that approach their aqueous saturated solubilities. These results strongly suggest that the behavioral actions of nonhalogenated alkane anesthetics do not result from their abilities to enhance agonist actions, directly activate, or inhibit α1β2γ2L GABAA receptors and are consistent with the hypothesis that electrostatic interactions between anesthetics and their protein binding sites modulate GABAA receptor potency.
Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies (1999)

The objective of this study was to establish a three-dimensional (3-D) in vitro model system of cardiac muscle for electrophysiological studies. Primary neonatal rat ventricular cells containing lower or higher fractions of cardiac myocytes were cultured on polymeric scaffolds in bioreactors to form regular or enriched cardiac muscle constructs, respectively. After 1 wk, all constructs contained a peripheral tissue-like region (50-70 micrometer thick) in which differentiated cardiac myocytes were organized in multiple layers in a 3-D configuration. Indexes of cell size (protein/DNA) and metabolic activity (tetrazolium conversion/DNA) were similar for constructs and neonatal rat ventricles. Electrophysiological studies conducted using a linear array of extracellular electrodes showed that the peripheral region of constructs exhibited relatively homogeneous electrical properties and sustained macroscopically continuous impulse propagation on a centimeter-size scale. Electrophysiological properties of enriched constructs were superior to those of regular constructs but inferior to those of native ventricles. These results demonstrate that 3-D cardiac muscle constructs can be engineered with cardiac-specific structural and electrophysiological properties and used for in vitro impulse propagation studies.
Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows. (1994)

Many brain tumors are highly resistant to chemotherapy, presumably due to the presence of a tight blood-tumor barrier. For a better understanding of the regulation of this barrier by the brain environment, a new intravital microscopy model was established by transplanting tumor tissue into cranial windows in both rats and mice. The model was characterized by RBC velocities, vessel diameters, and vascular permeabilities of various tumors: R3230AC (a rat mammary adenocarcinoma), MCaIV (a mouse mammary adenocarcinoma), and U87 and HGL21 (human malignant astrocytomas). Our results showed that tumor blood flow in cranial windows was one to three orders of magnitude lower than the blood flow in pial vessels and similar to that in dorsal skin-fold chambers observed in previous studies. The mean vessel diameter ranged from 6.8 +/- 1.3 microns for HGL21 to 30.4 +/- 8.5 microns for MCaIV. At least one order of magnitude difference in vascular permeability to albumin was observed between tumor lines: 0.11 +/- 0.05 x 10(-7) cm/s for HGL21 versus 3.8 +/- 1.2 x 10(-7) cm/s for U87. The low vascular permeability of HGL21, which was also confirmed by both sodium fluorescein and Lissamine green injections, suggests that not all tumors are leaky to tracer molecules and that the blood-tumor barrier of this tumor still possesses some characteristics of blood-brain barrier as observed in other intracranial tumors. The model presented here will allow us to manipulate the vascular permeability in brain tumors and thus may provide new information on the regulation of the blood-tumor barrier and new strategies for improving drug delivery in brain tumors.
Construction and Evaluation of a Safe, Live, Oral Vibrio cholerae Vaccine Candidate, IEM108 (2003)

ABSTRACT IEM101, a Vibrio cholerae O1 El Tor Ogawa strain naturally deficient in CTXΦ, was previously selected as a live cholera vaccine candidate. To make a better and safer vaccine that can induce protective immunity against both the bacteria and cholera toxin (CT), a new vaccine candidate, IEM108, was constructed by introducing a ctxB gene and an El Tor-derived rstR gene into IEM101. The ctxB gene codes for the protective antigen CTB subunit, and the rstR gene mediates phage immunity. The stable expression of the two genes was managed by a chromosome-plasmid lethal balanced system based on the housekeeping gene thyA . Immunization studies indicate that IEM108 generates good immune responses against both the bacteria and CT. After a single-dose intraintestinal vaccination with 10 9 CFU of IEM108, both anti-CTB immunoglobulin G and vibriocidal antibodies were detected in the immunized-rabbit sera. However, only vibriocidal antibodies are detected in rabbits immunized with IEM101. In addition, IEM108 but not IEM101 conferred full protection against the challenges of four wild-type toxigenic strains of V. cholerae O1 and 4 μg of CT protein in a rabbit model. By introducing the rstR gene, the frequency of conjugative transfer of a recombinant El Tor-derived RS2 suicidal plasmid to IEM108 was decreased 100-fold compared to that for IEM101. This indicated that the El Tor-derived rstR cloned in IEM108 was fully functional and could effectively inhibit the El Tor-derived CTXΦ from infecting IEM108. Our results demonstrate that IEM108 is an efficient and safe live oral cholera vaccine candidate that induces antibacterial and antitoxic immunity and CTXΦ phage immunity.
Fibronectin receptors from Streptococcus dysgalactiae and Staphylococcus aureus. Involvement of conserved residues in ligand binding. (1993)

The nucleotide sequence of two genes encoding fibronectin (Fn) receptors FnBA and FnBB of Streptococcus dysgalactiae S2 revealed the presence of repeated motifs (called RA1-A3 and RB1-B3, respectively) which encode Fn binding activity (Lindgren, P.-E., McGavin, M. J., Signäs, C., Guss, B., Gurusiddappa, S., Höök, M., and Lindberg, M. (1993) Eur. J. Biochem. 214, 819-827). Synthetic peptides of 32-37 amino acids, corresponding to individual repeated motifs, were assayed for the ability to inhibit Fn binding to cells of S. dysgalactiae. Within the RA motifs, peptide A2 was 10-fold more active than either A1 or A3, while in the RB motifs, only B3 was active. The same level of activity is observed when these synthetic peptides were assayed for inhibition of Fn binding to cells of Staphylococcus aureus. Likewise, synthetic peptides corresponding to the RD1-D3 motifs, which comprise a ligand binding domain in a Fn receptor from S. aureus, inhibit binding of Fn to both S. aureus and S. dysgalactiae. Assays of chemically modified peptides and peptide fragments derived from chemical or proteolytic cleavage suggest that a conserved core sequence, defined as ED(T/S) (X9,10)GG(X3,4)(I/V)DF, within a 30-amino acid-long segment is present in the active RA and RD motifs. Analyses of the importance of individual residues of this core sequence indicate that the ED(T/S) motif is nonessential, whereas the GG and the (I/V)DF together with additional acidic residues in the C-terminal half of the peptide are required for activity.
An ATM switching testbed (1991)

Abstract An experimental ATM switching node being developed by CSELT in the framework of CNR PFT is described. The node is built around a self‐routing buffered multistage switching network based oh a single type of integrated component. Each port of the network is connected to a packet processor which is in charge of interfacing with external ATM flows at 150 Mbit/s and of dealing with the ATM layer protocols. A distributed control structure is implemented, together with a software architecture which permits a rapid and easy introduction and testing of new services by abstracting system resources and defining a formal interface to application software. The access network developed within the ATM testbed is based on an active star shaped B‐NT which controls the access of the customer equipment to the local exchange and performs statistical multiplexing of the generated information flows. The terminals and interworking unit being provided in the ATM testbed have also been described, to give a picture of the services which will be considered in the experimentations.
Exhaustive 3D-QSAR analyses as a computational tool to explore the potency and selectivity profiles of thieno[3,2-d]pyrimidin-4(3H)-one derivatives as PDE7 inhibitors (2016)

In the development of selective ligands binding to specific PDE isoforms, the ligand-based approach proved to be a useful tool to better investigate the potency and selectivity profiles of PDE7 inhibitors.
Design and Synthesis of Novel Pyrrolo[2,1-c][1,4]benzodiazepine - Imidazole Containing Polyamide Conjugates (2002)

Article Design and Synthesis of Novel Pyrrolo[2,1-c][1,4]benzodiazepine - Imidazole Containing Polyamide Conjugates was published on February 1, 2002 in the journal Heterocyclic Communications (volume 8, issue 1).
Identification of Mycoplasma pirum genes involved in the salvage pathways for nucleosides (1993)

Genes encoding enzymes involved in the salvage pathway for nucleosides have been cloned and sequenced from the mollicute Mycoplasma pirum. One of them, encoding deoxyriboaldolase, was functionally identified by complementation of an Escherichia coli mutant. These genes are clustered, suggesting an operon organization, and they are immediately followed by the putative gene for the triose phosphate isomerase, an enzyme used during glycolysis.
Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial (2011)

Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With a median follow-up of 23 months, overall survival was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and janus kinase 2 (JAK2) genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1γ, did not predict response or survival on DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in approximately 40% of CMML patients with advanced myeloproliferative or myelodysplastic features and suggested that CJUN and CMYB expression could be potential biomarkers in this setting. This trial is registered at EudraCT (eudract.ema.europa.eu) as #2008-000470-21 and www.clinicaltrials.gov as #NCT01098084.
Bayesian classification with Gaussian processes (1998)

We consider the problem of assigning an input vector to one of m classes by predicting P(c|x) for c=1,...,m. For a two-class problem, the probability of class one given x is estimated by /spl sigma/(y(x)), where /spl sigma/(y)=1/(1+e/sup -y/). A Gaussian process prior is placed on y(x), and is combined with the training data to obtain predictions for new x points. We provide a Bayesian treatment, integrating over uncertainty in y and in the parameters that control the Gaussian process prior the necessary integration over y is carried out using Laplace's approximation. The method is generalized to multiclass problems (m>2) using the softmax function. We demonstrate the effectiveness of the method on a number of datasets.
Expressions of osteopontin (OPN), ανβ3 and Pim-1 associated with poor prognosis in non-small cell lung cancer (NSCLC) (2012)

OPN, (α) (ν) (β) (3) and Pim-1 proteins are frequently overexpressed in NSCLC, and they may play important roles in the development and/or progression of NSCLC.
Defeating Compensation in Wide Gap Semiconductors by Growing in H that is Removed by Low Temperature De-Ionizing Radiation (1992)

We propose a general method to obtain high conductivity of either type in wide gap semiconductors where compensation normally limits conductivity of one or both types. We suggest that the successes of Amano et al . and of Nakamura et al . in obtaining more than 10 18 cm -3 holes in GaN are particular examples of the general process that we propose.
Microstructural features and mechanical properties of carbon nanotubes reinforced aluminum–based metal matrix composites (2008)

The composites of aluminum-carbon nanotubes, produc
ed using catalytic chemical vapour deposition metho
d, are 
prepared with initial composition of aluminum homog
eneously mixed with 1, 2, 4 and 10wt% nanotubes and
 subsequently 
hot-pressed. TEMs and a STEM have been used to stud
y the as prepared carbon nanotubes and their distri
bution in 
aluminum matrix after reinforcement. A set of preli
minary observations delineated that the yield of as
 produced nanotubes 
in carbonaceous is very high with an average diamet
er of about 45 nm and with straight and spiral shap
es. In composites, 
these tubes have been seen uniformly distributed in
 aluminum matrix without any significant dimensiona
l alteration. An 
enormous increase in microhardness of aluminum – 10
wt% carbon nanotubes composites in contrast to pure
 aluminum has 
been a remarkable study. Some of the important micr
oscopic details, electrical measurements and mechan
ical properties in 
the nanotubes and their composites have been elucid
ated and discussed.
Plenoptic sampling (2000)

This paper studies the problem of plenoptic sampling in image-based rendering (IBR). From a spectral analysis of light field signals and using the sampling theorem, we mathematically derive the analytical functions to determine the minimum sampling rate for light field rendering. The spectral support of a light field signal is bounded by the minimum and maximum depths only, no matter how complicated the spectral support might be because of depth variations in the scene. The minimum sampling rate for light field rendering is obtained by compacting the replicas of the spectral support of the sampled light field within the smallest interval. Given the minimum and maximum depths, a reconstruction filter with an optimal and constant depth can be designed to achieve anti-aliased light field rendering. Plenoptic sampling goes beyond the minimum number of images needed for anti-aliased light field rendering. More significantly, it utilizes the scene depth information to determine the minimum sampling curve in the joint image and geometry space. The minimum sampling curve quantitatively describes the relationship among three key elements in IBR systems: scene complexity (geometrical and textural information), the number of image samples, and the output resolution. Therefore, plenoptic sampling bridges the gap between image-based rendering and traditional geometry-based rendering. Experimental results demonstrate the effectiveness of our approach.
A new device for administration of nasal continuous positive airway pressure in the newborn (1988)

During treatment with continuous positive airway pressure (CPAP), optimal re-expansion of lung units with minimal work of breathing is best accomplished when the airway pressure (Paw) is kept constant at the desired CPAP level throughout the entire breathing cycle. To achieve this, a new device was constructed in which CPAP was generated by a jet of fresh gas close to the nasal airway. The performance of the new device was investigated experimentally using a lung model which simulated the breathing pattern of a newborn. Paw, flow, and external work of breathing were measured at three CPAP levels, with and without controlled airway leakage. The new device was compared with a traditional continuous-flow CPAP system with standard nasal prongs. Despite a virtually constant pressure within the traditional system, Paw variations and external workload were considerably less with the new device, which was also less sensitive to airway leakage.
A fast MPEG video encryption algorithm (1998)

Article Free Access Share on A fast MPEG video encryption algorithm Authors: Changgui Shi Department of Computer Sciences, Purdue University, West Lafayette, IN Department of Computer Sciences, Purdue University, West Lafayette, INView Profile , Bharat Bhargava Department of Computer Sciences, Purdue University, West Lafayette, IN Department of Computer Sciences, Purdue University, West Lafayette, INView Profile Authors Info & Claims MULTIMEDIA '98: Proceedings of the sixth ACM international conference on MultimediaSeptember 1998 Pages 81–88https://doi.org/10.1145/290747.290758Online:01 September 1998Publication History 162citation2,346DownloadsMetricsTotal Citations162Total Downloads2,346Last 12 Months72Last 6 weeks18 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type (2000)

Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection have a persistent acute type lung inflammation dominated by polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P. aeruginosa. We speculated whether this immune response in CF is of the Th2 type and whether a change to a Th1 type immune response could improve the prognosis. Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF -P) chronic P. aeruginosa lung infection. The specific production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by peripheral blood mononuclear cells was determined. Cells from CF +P patients had lower IFN-gamma (p<0.05) and higher IL-4 (p<0.005) production as compared to cells from CF -P patients. Furthermore, a positive correlation between IFN-gamma production and lung function was found (FVC: Rho = 0.637; p<0.03; FEV1: Rho=0.524; p<0.07). We conclude that a Th2 type immune response is most frequent in CF patients with chronic P. aeruginosa lung infection, and the patients with a Th1-dominated immune response had the best lung function. The clinical implication is that a change to a Th1 type immune response might improve the prognosis in these patients.