gebhart/patrepeval huggingface dataset:
In Vitro Activities of Garenoxacin and Levofloxacin against Chlamydia pneumoniae Are Not Affected by Presence of Mycoplasma DNA (2004)

We studied 20 Chlamydia pneumoniae isolates obtained from respiratory sites and atheroma tissue of patients from various geographic areas to determine the susceptibilities of these isolates to a new des-fluoroquinolone, garenoxacin, and to levofloxacin. In addition, we assessed the cultures with these isolates by PCR for the presence or absence of Mycoplasma sp. DNA. Both the MIC at which 90% of isolates are inhibited (MIC(90)) and the minimal bactericidal concentration at which 90% of isolates are killed (MBC(90)) for garenoxacin were 0.06 microg/ml, and both the MIC(90) and the MBC(90) for levofloxacin were 2.0 microg/ml. The activity of garenoxacin against C. pneumoniae was 32-fold greater than that of levofloxacin. Mycoplasma sp. DNA was detected by PCR in 17 of 20 cultures. Mycoplasma amplicons from five Mycoplasma DNA-positive C. pneumoniae cultures were sequenced and found to represent four Mycoplasma species. Our data demonstrate that C. pneumoniae cultures frequently contain Mycoplasma DNA and that its presence in C. pneumoniae cultures does not appear to affect the susceptibility results for the two fluoroquinolones that we tested.
Activity promotion for community-dwelling older people: a survey of the contribution of primary care nurses (2011)

Study aims: To discover the current level of nurse-led involvement in activity promotion for older people in primary care and to explore the knowledge and attitudes of primary care nurses about health benefits of activity promotion for older people. Background: The importance of improving and maintaining activity levels in later life is well established. However, intervention studies show that the uptake of and adherence to physical activity programmes by older people are highly variable. The optimal approach to activity promotion for older people is not well understood. Although many activity promotion schemes and evaluations assume that specialist exercise trainers are needed, it remains unclear who is best placed to facilitate activity promotion for older people, and if this is something in which existing primary care practitioners (specifically nurses) could and should take a leading role. Methods: This study surveyed all nurses and health visitors working in five primary care organizations in an inner city area. A semi-structured postal questionnaire asked about their knowledge and attitudes to the benefits of exercise in later life, their current levels of involvement in promoting physical activity with older people, and their personal activity levels. Findings: The overall response rate was 54% (n=521). The responses of 391 district nurses and practice nurses are presented here. Nurses had the commitment and (depending on the focus of their work) different opportunities to promote physical activity with older patients. There were organizational and individual constraints on their ability to be involved in this aspect of health promotion work themselves, or to refer older people to local activity promotion schemes. Nurses did not have a structured approach when promoting physical activity with older people and had only a partial awareness of the limitations of their knowledge or skills when promoting activity with older people. Conclusions: For promotion of physical activity by older people to be meaningfully incorporated into primary care nursing work there is a need to develop a more strategic approach that can optimize the opportunities and interest of primary care nurses and develop the knowledge and skills of the workforce in this area of nursing work.
Nonlinear refraction traveltime tomography (1998)

Abstract A few important issues for performing nonlinear refraction traveltime tomography have been identified. They include the accuracy of the traveltime and raypath calculations for refraction, the physical information in the refraction traveltime curves, and the characteristics of the refraction traveltime errors. Consequently, we develop a shortest path ray-tracing method with an optimized node distribution that can calculate refraction traveltimes and raypaths accurately in any velocity model. We find that structure ambiguity caused by short and long rays in the seismic refraction method may influence the inversion solution significantly. Therefore, we pose a nonlinear inverse problem that explicitly minimizes the misfits of the average slownesses (ratios of traveltimes to the corresponding ray lengths) and the apparent slownesses (derivatives of traveltimes with respect to distance). As a result, we enhance the resolution as well as the convergence speed. To regularize our inverse problem, we use the Tikhonov method to avoid solving an ill-posed inverse problem. Errors in refraction traveltimes are characterized in terms of a common-shot error, a constant deviation for recordings from the same shot, and a relative traveltime-gradient error with zero mean with respect to the true gradient of the traveltime curve. Therefore, we measure the uncertainty of our tomography solution using a nonlinear Monte Carlo approach and compute the posterior model covariance associated with two different types of random data vectors and one random model vector. The nonlinear uncertainty analysis indicates that the resolution of a tomography solution may not correspond to the ray coverage. We apply this tomography technique to image the shallow velocity structure at a coastal site near Boston, Massachusetts. The results are consistent with a subsequent drilling survey.
In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells (2007)

Following removal of the primary breast tumour by conservative surgery, patients may still have additional malignant foci scattered throughout the breast. Radiation treatments are not designed to eliminate all these residual cancer cells. Rather, the radiation dose is calculated to optimise long-term results with minimal complications. In a tumour, cancer cells are surrounded by a basement membrane, which plays an important role in the regulation of gene expression. Using an invasion chamber, we have shown that irradiation before cell plating of a reconstituted basement membrane (Matrigel; Becton Dickinson, Bedford, MA, USA) increased the invasiveness of the breast cancer cells MDA-MB-231. This radiation enhancement of invasion was associated with the upregulation of the pro-invasive gene matrix metalloproteinase (MMP)-2. The expression of membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitor of metalloproteinase-2 (TIMP), which are required to activate the MMP-2, were also increased. Confirming the role of MMP-2 and MT1-MMP, radiation enhancement of cancer cell invasion was prevented by an MMP-2 inhibitor and an anti-MT1-MMP antibody. This study also demonstrated that radiation can potentially enhance the invasion ability by inducing the release of pro-invasive factors stored in the Matrigel. Conversely, no enhancement of invasiveness was observed with the low metastatic cell line MCF-7. This lack of invasiveness correlated with the absence of the MMP-2 activator MT1-MMP in the MCF-7 cells. Radiotherapy is an efficient modality to treat breast cancer which could be further improved by inhibiting the pro-invasive gene upregulated by radiation.
RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies (2012)

Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration of leukocytes into the central nervous system, the clinical symptoms of relapses, remissions and progressive paralysis are the result of losses of myelin and neurons. In the absence of etiological factors as targets for prevention and therapy, the definition of molecular mechanisms that form the basis of inflammation, demyelination and toxicity for neurons have led to a number of treatments that slow down disease progression in specific patient cohorts, but that do not cure the disease. Current therapies are directed to block the immune processes, both innate and adaptive, that are associated with multiple sclerosis. In this review, we analyze the role of cytokines in the multiple sclerosis pathogenesis and current/future use of them in treatments of multiple sclerosis.
Fully digital neural network implementation based on pulse density modulation (1989)

An efficient implementation of a Hopfield-type fully connected neural-network architecture is presented that is based on a pulse-density modulation technique implemented by using fully digital structures. The synaptic weights are programmable, and thus the area of one synapse and the entire network depends on the resolution of the weight. Advantages of the design are its modularity and expandability
The Genomes of Oryza sativa: A History of Duplications (2005)

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin (1990)

A novel class of synthetic peptides has been designed that inhibit the thrombin catalytic site and exhibit specificity for the anion-binding exosite (ABE) of alpha-thrombin. These peptides, called "hirulogs", consist of (i) an active-site specificity sequence with a restricted Arg-Pro scissile bond, (ii) a polymeric linker of glycyl residues from 6 to 18 A in length, and (iii) an ABE recognition sequence such as that in the hirudin C-terminus. Hirulog-1 ([D-Phe)-Pro-Arg-Pro-(Gly)4-Asn-Gly-Asp-Phe-Glu-Glu-Ile- Pro-Glu-Tyr-Leu] inhibits the thrombin-catalyzed hydrolysis of a tripeptide p-nitroanilide substrate with Ki = 2.3 nM. In contrast, the synthetic C-terminal hirudin peptide S-Hir53-64, which binds to the thrombin ABE, blocked the fibrinogen clotting activity of the enzyme with Ki = 144 nM but failed to inhibit the hydrolysis of p-nitroanilide substrates at concentrations as high as 1 mM. In addition, the pentapeptide (D-Phe)-Pro-Arg-Pro-Gly, which comprises the catalytic-site inhibitor moiety of hirulog-1, was determined to have a Ki for thrombin inhibition greater than 2 microM. Hirulog-1, but not S-Hir53-64, was found to inhibit the incorporation of [14C]diisopropyl fluorophosphate in thrombin. Hirulog-1 appears specific for thrombin as it lacks inhibitory activities toward human factor Xa, human plasmin, and bovine trypsin at inhibitor:enzyme concentrations 3 orders of magnitude higher than those required to inhibit thrombin. The optimal inhibitory activity of hirulog-1 depends upon all three components of its structure.(ABSTRACT TRUNCATED AT 250 WORDS)
High-impedance electromagnetic surfaces for parallel-plate mode suppression in high-speed digital systems (2003)

This paper discusses the application of high-impedance electromagnetic surfaces (HIS) for EMI shielding in high-speed circuits. The limitations of the HIS with straight vias are investigated and an improved solution proposed. The new solution can mitigate noise from DC up to 4 GHz.
Ethanol Pharmacokinetics in White Women: Nonlinear Model Fitting Versus Zero‐Order Elimination Analyses (2000)

After multiple dose ingestion in white women, classical zero-order elimination analyses can be applied only to a limited portion of the descending BrAC-time curve. They seem justified and practical from 0.5 hr after peak BrAC until BrAC reaches 0.2 g x L(-1). To describe ethanol pharmacokinetics across the entire BrAC-time curve, however, sophisticated nonlinear model fitting is required.
Photocontrol of DNA Binding Specificity of a Miniature Engrailed Homeodomain (2005)

Control of DNA binding of HDH-3, a 18-residue polypeptide based on the recognition helix of the Q50K engrailed homeodomain, has been achieved. HDH-3 was linked to an azobenzene cross-linker through two cysteine residues in an i, i + 11 spacing. For the thermodynamically stable trans configuration of the cross-linker, the dark-adapted peptide (dad-HDH-3) adopted a mainly alpha-helical structure as judged by circular dichroism (CD) spectroscopy. After irradiation with light of 360 nm, the helical content of the peptide (irrad-HDH-3) was reduced significantly and the CD spectrum of the irradiated peptide resembled that of the largely unstructured, unalkylated peptide. Despite lacking helices-1 and -2 and the N-terminal arm of Q50K engrailed, dad-HDH-3 bound to its natural DNA target sequence TAATCC (QRE) with high affinity (K(D) = 7.5 +/- 1.3 nM). The binding affinity for the mutant DNA sequence, TAATTA (ERE), was reduced significantly (K(D) = 140 +/- 11 nM). Unlike irrad-HDH-3, which like the unalkylated parent peptide displayed only marginal DNA binding specificity, dad-HDH-3 specified base pairs 5 and 6 of QRE with an accuracy rivaling that of the intact wild-type Q50K engrailed homeodomain, making dad-HDH-3 the most specific designed DNA binding miniature homeodomain reported to date. Moreover, DNA binding affinity and specificity of HDH-3 could be controlled externally by irradiation with light.
A Light-Activated Probe of Intracellular Protein Kinase Activity (2003)

The first example of a photoactivated probe of intracellular enzymatic activity is described. The caged derivative of a fluorescent protein kinase C peptide-based sensor was prepared by modifying the free hydroxyl group of a phosphorylatable serine moiety with a photolabile appendage that blocks phosphoryl transfer. We have demonstrated that the caged sensor allows one to (1) sample PKC activity with exquisite temporal precision, (2) control the relative amount of active sensor available for phosphorylation, and (3) examine protein kinase activity at multiple time points.
A study of the effect of JPG compression on adversarial images (2016)

Neural network image classifiers are known to be vulnerable to adversarial images, i.e., natural images which have been modified by an adversarial perturbation specifically designed to be imperceptible to humans yet fool the classifier. Not only can adversarial images be generated easily, but these images will often be adversarial for networks trained on disjoint subsets of data or with different architectures. Adversarial images represent a potential security risk as well as a serious machine learning challenge---it is clear that vulnerable neural networks perceive images very differently from humans. Noting that virtually every image classification data set is composed of JPG images, we evaluate the effect of JPG compression on the classification of adversarial images. For Fast-Gradient-Sign perturbations of small magnitude, we found that JPG compression often reverses the drop in classification accuracy to a large extent, but not always. As the magnitude of the perturbations increases, JPG recompression alone is insufficient to reverse the effect.
Spinocerebellar ataxia type-1 and spinobulbar muscular atrophy gene products interact with glyceraldehyde-3-phosphate dehydrogenase (1996)

Spinocerebellar ataxia type1 (SCA1) is one of several neurodegenerative disorders caused by expansions of translated CAG trinucleotide repeats which code for polyglutamine in the respective proteins. Most hypotheses about the molecular defect in these disorders suggest a gain of function, which may involve interactions with other proteins via the expanded polyglutamine tract. In this study we used ataxin-1, the SCA1 gene product, as a bait in the yeast two-hybrid system and identified the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase as an ataxin-1 interacting protein. In addition, the yeast two hybrid data demonstrate that wild type and mutant ataxin-1 form homo and heterodimers. Physical interaction between GAPDH and ataxin-1 was also demonstrated in vitro. To investigate if GAPDH might interact with other glutamine repeat-containing proteins involved in neurodegenerative disorders, we tested its binding to the androgen receptor which is mutated in spinobulbar muscular atrophy. The androgen receptor interacts with GAPDH both in the yeast two-hybrid system and in vitro. The binding of both ataxin-1 and the androgen receptor to GAPDH does not vary with the length of the polyglutamine tract. While provocative, these findings do not address the selective neuronal loss in each of these disorders in light of the wide expression patterns of GAPDH and the respective polyglutamine containing proteins. Nonetheless, such interactions may increase the susceptibility of specific neurons to a variety of insults and initiate degeneration.
CNS 7056 (2007)

CNS 7065 is a high-affinity and selective ligand for the benzodiazepine site on the GABAA receptor. CNS 7056 does not show selectivity between GABAA receptor subtypes. CNS 7056 is a potent sedative in rodents with a short duration of action. Inhibition of substantia nigra pars reticulata firing and the inhibition of the effects of CNS 7056 by flumazenil show that it acts at the brain benzodiazepine receptor.
Scanning probe lithography tips with spring-on-tip designs: Analysis, fabrication, and testing (2005)

This letter reports a special tip design for probes used in scanning probe lithography applications. The sidewalls of the pyramidal tip located at the distal end of a cantilever probe are modified to contain folded spring structures to reduce the overall force constant of the scanning probe. The spring structure is generated using focused ion beam milling method. We have conducted finite element simulation of the force constants of such folded springs under various geometries. We also demonstrated sub-100nm scanning probe lithography using a modified spring tip in the dip pen nanolithography writing mode.
Dissemination-Oriented Communication Systems. (1996)

Abstract : This is the final report for ARPA contract no. DABT63-91-K-0001. This contract was focused on exploring dissemination oriented communication systems, systems in which the primary mode of communication was based on publishing information sources multicasting to subscribing sources. The approach was develop new protocols at the network, transport, session and presentation layers, and evaluate these protocol designs by implementation and use with a few sample dissemination applications that are also being developed. The objective was to design a next generation communication protocol architecture for dissemination oriented communication that was applicable in a wide variety of (inter)networks, ranging from high speed, high delay terrestrial to low speed, high error rate mobile networks. We started the contract with some basic ideas of how to revise the various protocol levels to support the dissemination model, based on our prior experience with IP multicast, VMTFP and application-layer protocols. Over time, these ideas were refined such that some were incorporated into a common protocol, others were discarded as unworkable or suboptimal. and some were realized as originally proposed. It would probably be politic to claim we are highly successful in every aspect of the original proposed work. However, usually some of the greatest insights and progress come from mistakes, and in that vein, we had lots of insights and progress. In this report, we also try to be honest and clear about how some of our original proposed directions failed, and why. The following sections describe the results for each of the original deliverables, plus sections corresponding to what we actually developed, if that was different from originally proposed. We first describe some background ideas and how their development affected our work on this contract.
Human lipopolysaccharide-binding protein potentiates bactericidal activity of human bactericidal/permeability-increasing protein (1995)

Human bactericidal/permeability-increasing protein (BPI) from neutrophils and a recombinant amino-terminal fragment, rBPI23, bind to and are cytotoxic for gram-negative bacteria both in vitro and ex vivo in plasma or whole blood. To function in vivo as an extracellular bactericidal agent, rBPI23 must act in the presence of the lipopolysaccharide-binding protein (LBP), which also binds to but has no reported cytotoxicity for gram-negative bacteria. LBP, which is present at 5 to 10 micrograms/ml in healthy humans and at much higher levels in septic patients, mediates proinflammatory host responses to gram-negative infection. On the basis of these previous observations, we have examined the effect of recombinant LBP (rLBP) on the bactericidal activity of rBPI23 against Escherichia coli J5 in vitro. Physiological concentrations of rLBP (5 to 20 micrograms/ml) had little or no bactericidal activity but reduced by up to approximately 10,000-fold the concentration of BPI required for bactericidal or related activities in assays which measure (i) cell viability as CFUs on solid media or growth in broth culture and (ii) protein synthesis following treatment with BPI. LBP also potentiated BPI-mediated permeabilization of the E. coli outer membrane to actinomycin D by about 100-fold but had no permeabilizing activity of its own. Under optimal conditions for potentiation, fewer than 100 BPI molecules were required to kill a single E. coli J5 bacterium.