gebhart/patrepeval huggingface dataset:
A Functional dlt Operon, Encoding Proteins Required for Incorporation of d -Alanine in Teichoic Acids in Gram-Positive Bacteria, Confers Resistance to Cationic Antimicrobial Peptides in Streptococcus pneumoniae (2006)

Streptococcus pneumoniae is one of the few species within the group of low-G +C gram-positive bacteria reported to contain no d-alanine in teichoic acids, although the dltABCD operon encoding proteins responsible for d-alanylation is present in the genomes of two S. pneumoniae strains, the laboratory strain R6 and the clinical isolate TIGR4. The annotation of dltA in R6 predicts a protein, d-alanine-d-alanyl carrier protein ligase (Dcl), that is shorter at the amino terminus than all other Dcl proteins. Translation of dltA could also start upstream of the annotated TTG start codon at a GTG, resulting in the premature termination of dltA translation at a stop codon. Applying a novel integrative translation probe plasmid with Escherichia coli 'lacZ as a reporter, we could demonstrate that dltA translation starts at the upstream GTG. Consequently, S. pneumoniae R6 is a dltA mutant, whereas S. pneumoniae D39, the parental strain of R6, and Rx, another derivative of D39, contained intact dltA genes. Repair of the stop codon in dltA of R6 and insertional inactivation of dltA in D39 and Rx yielded pairs of dltA-deficient and dltA-proficient strains. Subsequent phenotypic analysis showed that dltA inactivation resulted in enhanced sensitivity to the cationic antimicrobial peptides nisin and gallidermin, a phenotype fully consistent with those of dltA mutants of other gram-positive bacteria. In addition, mild alkaline hydrolysis of heat-inactivated whole cells released d-alanine from dltA-proficient strains, but not from dltA mutants. The results of our study suggest that, as in many other low-G+C gram-positive bacteria, teichoic acids of S. pneumoniae contain d-alanine residues in order to protect this human pathogen against the actions of cationic antimicrobial peptides.
Quasi-phase-matched second-harmonic generation of blue light in periodically poled LiNbO3 (1990)

LiNbO3 crystals with periodically alternating ferroelectric domains have been produced using laser-heated pedestal growth. Domain thicknesses as small as 1 μm have been achieved. This material was applied to room-temperature, quasi-phase-matched frequency doubling to generate light at wavelengths as short as 407 nm, using the d33 and d22 nonlinear coefficients. The measured conversion efficiencies and wavelength and temperature tuning bandwidths are consistent with an effective interaction length of ≊320 μm (&amp;gt;230 domains). An initial test with high-intensity focused blue beams showed that the periodically poled material exhibits no discernible photorefractive damage effect.
Downregulation of HER3: A potential surrogate for activation of HER2 through heterodimerization may predict clinical benefit in ovarian cancer from pertuzumab, a HER dimerization inhibiting antibody (2007)

C141 Pertuzumab is a humanized monoclonal antibody designed to block HER2’s ability to dimerize with ligand activated HER receptors like HER3. Pre-clinical studies indicated that pertuzumab may have activity in a subset of tumors where HER2 is activated through ligand-induced heterodimerization. Furthermore, these studies indicate that mRNA expression levels of HER2 and/or HER3 might serve as surrogate markers for HER2 pathway activity. To avoid an invasive tumor biopsy, a qRT-PCR assay was developed for mRNA expression analysis of HER pathway genes using archival formalin fixed paraffin embedded tissue (FFPET).  To explore the activity of pertuzumab, particularly in patient subsets defined by potential diagnostic biomarkers, a randomized phase II trial in platinum-resistant ovarian cancer, comparing gemcitabine + placebo to gemcitabine + pertuzumab was conducted (N=130) (ASCO 2007, abstract #5507). The overall treatment benefit from adding pertuzumab to gemcitabine was modest, with a PFS hazard ratio (HR) of 0.66 (95% CI: 0.43-1.03, p=0.07) and a median duration PFS of 2.6 vs. 2.9 months. mRNA expression data from archival tumor tissues, analyzing EGFR, HER2, HER3 and several HER ligands was generated from 122/130 patients’ tumors and compared to clinical outcomes. The PFS hazard ratio of 0.13 (95% CI: 0.04-0.41, p=
Discovery of 2-Hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5- methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123):  A Potent, Orally Bioavailable CXCR2/CXCR1 Receptor Antagonist (2006)

Structure-activity studies on lead cyclobutenedione 3 led to the discovery of 4 (SCH 527123), a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist with excellent cell-based activity. Compound 4 displayed good oral bioavailability in rat and may be a potential therapeutic agent for the treatment of various inflammatory diseases.
The safety of treatment with recombinant human erythropoietin in clinical use: a review of controlled studies. (1998)

Recombinant human erythropoietin (rhEPO) has now been approved for the treatment of renal anemia, anemia of prematurity, cancer-associated anemia, AIDS-associated anemia and as concomitant treatment for patients with or without autologous blood donation awaiting elective surgery. The purpose of this review is to provide an overview, based on the results of controlled studies, of the anticipated safety profile of rhEPO in various indications and to assess whether treatment with rhEPO influences the incidences of certain adverse events in these indications. The anticipated adverse events differ from indication to indication and generally reflect the corresponding underlying illness. With most indications, no relevant differences in the incidences of adverse events are observed between rhEPO and placebo-control/patients. Only in the rhEPO therapy of renal anemia is an increased incidence of hypertensive events observed in the rhEPO groups, a finding that is not reproduced with the other indications. The controlled studies forming the basis of this review provide no evidence of a relevant increase in the risk of thromboembolic events during rhEPO therapy. Overall, it may be stated that rhEPO treatment, where strictly indicated, is a safe form of therapy. As with any other treatment, the risk of side effects in certain predisposed patients must also be weighed against the desired clinical benefits.
Appearance-based object recognition using multiple views (2005)

Object recognition from a single view fails when the available features are not sufficient to determine the identity of a single object, either because of similarity with another object or because of feature corruption due to clutter and occlusion. Active object recognition systems have addressed this problem successfully, but they require complicated systems with adjustable viewpoints that are not always available. In this paper we investigate the performance gain available by combining the results of a single view object recognition system applied to imagery obtained from multiple fixed cameras. In particular, we address performance in cluttered scenes with varying degrees of information about relative camera pose. We argue that a property common to many computer vision recognition systems, which we term a weak target error, is responsible for two interesting limitations of multi-view performance enhancement: the lack of significant improvement in systems whose single-view performance is weak, and the plateauing of performance improvement as additional multi-view constraints are added.
TCR‐induced T cell activation leads to simultaneous phosphorylation at Y505 and Y394 of p56lck residues (2012)

Biochemical studies have demonstrated that phosphorylation of lymphocyte cell kinase (p56(lck) ) is crucial for activation of signaling cascades following T cell receptor (TCR) stimulation. However, whether phosphorylation/dephosphorylation of the activating or inhibitory tyrosine residues occurs upon activation is controversial. Recent advances in intracellular staining of phospho-epitopes and cytometric analysis, requiring few cells, have opened up novel avenues for the field of immunological signaling. Here, we assessed p56(lck) phosphorylation, using a multiparameter flow-cytometric based detection method following T cell stimulation. Fixation and permeabilization in conjunction with zenon labeling technology and/or fluorescently labeled antibodies against total p56(lck) or cognate phospho-tyrosine (pY) residues or surface receptors were used for detection purposes. Our observations showed that activation of Jurkat or primary human T cells using H(2) O(2) or TCR-induced stimulation led to simultaneous phosphorylation of the activating tyrosine residue, Y394 and the inhibitory tyrosine residue, Y505 of p56(lck) . This was followed by downstream calcium flux and expression of T cell activation markers; CD69 and CD40 ligand (CD40L). However, the extent of measurable activation readouts depended on the optimal stimulatory conditions (temperature and/or stimuli combinations). Treatment of cells with a p56(lck) -specific inhibitor, PP2, abolished phosphorylation at either residue in a dose-dependent manner. Taken together, these observations show that TCR-induced stimulation of T cells led to simultaneous phosphorylation of p56(lck) residues. This implies that dephosphorylation of Y505 is not crucial for p56(lck) activity. Also, it is clear that cytometric analysis provides for a rapid, sensitive, and quantitative method to supplement biochemical studies on p56(lck) signaling pathways in T cells at single cell level.
Helix-Inducing α-Aminoisobutyric Acid in Opioid Mimetic Deltorphin C Analogues (1997)

The achiral symmetric alpha-aminoisobutyric acid (Aib) replaced the critical N-terminal residues of the amphibian skin opioid deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) without detriment to the physicochemical requirements for delta opioid receptor recognition. Substitutions by the alpha, alpha-dialkyl amino acid in place of D-Ala2 or Phe3, or both, exhibited high delta receptor affinity (Ki delta = 0.12-3.6 nM) and 5-9-fold greater selectivity (Ki mu/Ki delta = 5000-8500) than the parent compound. This is the first definitive demonstration that the D-chirality of alanine and the aromaticity of phenylalanine are replaceable by an achiral alpha, alpha-dialkylated residue without detrimental effects on ligand binding. Incorporation of the mono-alpha-alkyl amino acid L- or D-Ala at the third position also produced highly selective delta ligands (Ki mu/Ki delta = 2000-3500), albeit with reduced delta affinities (Ki delta = 6-15 nM). Replacement of the anionic residue Asp4 by Aib yielded an opioid peptide that fit two-site binding models for the delta receptor (eta = 0.763; P < 0.0001) and displayed dual high affinity for both delta and mu receptors, emphasizing the repulsive effect by a negative charge at mu receptor sites and the insignificance of Asp for delta affinity. Molecular dynamics conformation analyses suggested that Aib residues caused distinct changes in deltorphin C secondary structure when substituted for D-Ala2, Asp4, and simultaneously D-Ala2 and Phe3 but not when substituted for Phe3. These conformational changes might be critical factors for the proper orientation of reactive constituents of residues in the N-terminal region of deltorphin C. Disparities between binding data and functional bioassays of [Aib3] indicated that Phe3 was required for bioactivity in mouse vas deferens but not for interaction with delta opioid receptors in rat brain membranes.
CONFAC: automated application of comparative genomic promoter analysis to DNA microarray datasets (2004)

The advent of DNA microarray technology and the sequencing of multiple vertebrate genomes has provided a unique opportunity for the integration of comparative genomics with high-throughput gene expression analysis. Here we describe the conserved transcription factor binding site (CONFAC) software that enables the high-throughput identification of conserved transcription factor binding sites (TFBSs) in the regulatory regions of hundreds of genes at a time (http://morenolab.whitehead.emory.edu/cgi-bin/confac/login.pl). The CONFAC software compares non-coding regulatory sequences between human and mouse genomes to enable identification of conserved TFBSs that are significantly enriched in promoters of gene clusters from microarray analyses compared to sets of unchanging control genes using a Mann-Whitney U-test. Analysis of random gene sets demonstrated that using our approach, over 98% of TFBSs had false positive rates below 5%. As a proof-of-principle, we have validated the CONFAC software using gene sets from four separate microarray studies and identified TFBSs known to be functionally important for regulation of each of the four gene sets.
Thrombophilia, Clinical Factors, and Recurrent Venous Thrombotic Events (2005)

Prothrombotic abnormalities do not appear to play an important role in the risk of a recurrent thrombotic event. Testing for prothrombotic defects has little consequence with respect to prophylactic strategies. Clinical factors are probably more important than laboratory abnormalities in determining the duration of anticoagulation therapy.
Radio-Frequency-Sputtered Films of β-Tungsten Structure Compounds (1970)

Radio-frequency sputtering has been used to deposit films of intermetallic binary systems (AxBy) in which the composition varies continuously from about 10 at.% to 80 at.% for the B constituent. Within this composition range the following β-tungsten structured compounds were obtained: V3Si, Nb3Sn, Nb3Pt, Nb3Au, Nb3Al, Nb3Ge, and Ta3Ge. For films with thickness ranging from 3000 to 10 000 Å values of Tc were observed which were within 1°K of previously reported best bulk values. In the case of Ta3Ge a new β-W superconductor has been found with a Tc of about 8°K.
Screening. The next century (1995)

New techniques will make it possible to screen high risk, low-income populations for cervical cancer and its precursors and to do so more cost-effectively than is possible using conventional Western approaches. In addition, the latest technology can enhance the screening methods traditionally used in industrialized countries and can increase the positive and negative predictive value of the screening method.
Selvfortolkende dyr (1970)

Oversat af Birgitte Eskildsen
Large orbit magnetic confinement systems for advanced fusion fuels (1992)

The objective of the grant/contract was to illuminate the problem of magnetic confinement for plasmas where the majority of ions have large gyro-orbits and do not obey adiabatic particle dynamics. The electrons are adiabatic. We considered a class of equilibria where large orbit ions dominate; the equilibria are rigorous solutions of the Vlasov/Maxwell equations. For a simple cse -- the infinitely long, low beta, rotating plasma a complete stability analysis was carried out. This problem was the basis of the first paper on finite Larmor radius stabilization. In that paper an expansion in {var epsilon} = {bar {alpha}}{sub i}/r{sub o} was carried out to the first significant order beyond MHD. In this report the same problem is solved to all orders in {var epsilon}. While this case is of limited applicability to experiments it is rigorous and without approximations, so that it can be used to verify approximations to be developed for more complex and useful cases. The application of the results to date to small fusion reactors is described in the second paper which was written after the termination of the contract, but is based in part on material developed during the contract period.
An integrated system for therapy planning of high intensity focused ultrasound (2008)

High intensity focused ultrasound (HIFU) has been developed and clinically used as a non-invasive cancer tumor treatment alternative. As compared to more commonly used cancer treatments such as surgery and radiation therapy, HIFU has the advantages of being minimally evasive and resulting in significantly less side-effect[1]. Clinical applications of HIFU have seemed promising success in organs like the prostate[2] and the breasts[3]. Nevertheless, organ-specific and patient-specific therapy planning and precise control of the HIFU lesion remain challenging issues. In this study, we address these issues by an integrated HIFU surgical planning system which is based on pre-surgical imaging, segmentation, HIFU beam and bioheat-transfer equation (BHTE) modeling and monitored exposure. Compared to published similar approaches [4], our system has the potential advantage of being more precise and accurate in delivering HIFU into target area.
HIV Tat Peptide Enhances Cellular Delivery of Antisense Morpholino Oligomers (2003)

Phosphorodiamidate morpholino oligomers (PMO) are uncharged antisense molecules that bind complementary sequences of RNA, inhibiting gene expression by preventing translation or by interfering with pre-mRNA splicing. The techniques used to deliver PMO into cultured cells have been mostly mechanical methods. These delivery methods, although useful, have limitations. We investigated the ability of the HIV Tat peptide (pTat) and other cationic peptides to deliver PMO into cultured cells. Fluorescence was seen in 100% of HeLa cells treated with pTat-PMO-fluorescein conjugate. pTat-PMO conjugate targeted to c-myc mRNA downregulated c-myc reporter gene expression with an IC50 of 25 microM and achieved nearly 100% inhibition. pTat-PMO conjugate targeted to a mutant splice site of beta-globin pre-mRNA dose-dependently corrected splicing and upregulated expression of the functional reporter gene. Neither unconjugated PMO nor unconjugated pTat caused antisense activities. However, compared with mechanically mediated delivery, pTat-mediated PMO delivery required higher concentrations of PMO (>10 microM) to cause antisense activity and caused some toxicity. Most pTat-PMO conjugate was associated with cell membranes, and internalized conjugate was localized in vesicles, cytosol, and nucleus. The other three cationic peptides are much less effective than pTat. pTat significantly enhances delivery of PMO in 100% of cells assayed. pTat-mediated delivery is a much simpler procedure to perform than other delivery methods.
Transcatheter Closure of Right-to-Left Interatrial Shunts to Resolve Hypoxemia (2008)

Transcatheter closure of right-to-left shunts is well-tolerated and a rewarding approach. It should be applied in selected patients following careful morphologic and hemodynamic evaluation. Tolerance of temporary occlusion of the defect is predictive of a favorable procedural outcome.
Complement-mediated adipocyte lysis by nephritic factor sera. (1993)

Recent data indicate a previously unsuspected link between the complement system and adipocyte biology. Murine adipocytes produce key components of the alternative pathway of complement and are able to activate this pathway. This suggested to us an explanation for adipose tissue loss in partial lipodystrophy, a rare human condition usually associated with the immunoglobulin G(IgG) autoantibody nephritic factor (NeF) which leads to enhanced alternative pathway activation in vivo. We hypothesized that in the presence of NeF, there is dysregulated complement activation at the membrane of the adipocyte, leading to adipocyte lysis. Here we show that adipocytes explanted from rat epididymal fat pads are lysed by NeF-containing sera but not by control sera. A similar pattern is seen with IgG fractions of these sera. Adipocyte lysis in the presence of NeF is associated with the generation of fluid-phase terminal complement complexes, the level of which correlates closely with the level of lactate dehydrogenase, a marker of cell lysis. Lysis is abolished by ethylenediaminetetraacetic acid, which chelates divalent cations and prevents complement activation, and reduced by an antibody to factor D, a key component of the alternative pathway. These data provide an explanation for the previously obscure link between NeF and fat cell damage.
Caged RNA: photo-control of a ribozyme reaction (1998)

We report here the first photo-chemical control of a ribozyme reaction by the site-specific modification of the 2'-hydroxyl nucleophile in the hammerhead system with a caging functionality. Rapid laser photolysis of the O-(2-nitrobenzyl) caging group initiates an efficient and accurate hammerhead-catalyzed cleavage of substrate RNA under native conditions. RNAs in which reactive functionalities or recognition elements are caged in this manner will be useful tools to probe RNA reactivity and dynamics.
An X-Linked Recessive Cardiomyopathy with Abnormal Mitochondria (1979)

A transvascular endomyocardial biopsy from an infant with cardiomyopathy and chronic congestive heart failure showed abnormal mitochondria when examined by electron microscopy. At necropsy, similar abnormal mitochondria were seen in skeletal muscles, liver, and kidney. The patient's family pedigree revealed several male babies who had cardiac disease and died in infancy. Myocardium obtained at necropsy from three cousins contained mitochondria with abnormalities similar to those from the proband. An X-linked recessive cardiomyopathy seems likely in this family.
Inheritance of certain fruit and seed characters in watermelons (1937)

does not appear. First page follows. Introduction With the increased interest being manifested in the development of new varieties of watermelons, Citrullus vulgaris (Schrad.), additional information is needed on the mode of inheritance of certain quantitative and qualitative characters. Many of the newer strains resistant to Fusarium wilt have resulted from hybridization of parents of diverse foliage, fruit, and seed characters. As experience has demonstrated, it is possible to establish and maintain resistance, but more difficult to purify new strains with respect to certain other characters. The plant breeder should not release resistant strains to the trade until they are relatively homozygous for seed characters, fruit type, fruit-skin color, and are uniformly satisfactory in quality. The mode of inheritance has a definite bearing on the problem. The watermelon has not been extensively analyzed genetically or cytologically, probably because of the relatively large area of land necessary to mature fruits in sufficient quantity to provide a population for genetic analysis. The crop is somewhat limited, furthermore, by regional adaptation and by the length of the growing season; and it is not particularly high in food value. Of the many varieties of watermelons known, relatively few are grown extensively. Regional adaptation, market preference, and wilt resistance determine the variety or varieties preferable for a particular district. In the North, where frosts occur early in the fall, quick-maturing varieties are needed. Southern districts favor varieties with a tough (usually thick) rind suited for shipment to the northern markets.
Physiological and cytokine responses in IL-1 beta-deficient mice after zymosan-induced inflammation (1997)

Interleukin (IL)-1 beta-deficient (IL-1 beta -/-) mice exhibited decreased zymosan-induced lethality and reduced production of IL-6 compared with wild-type controls (IL-1 beta +/+). In addition, IL-1 beta -/- mice had a diminished cellular infiltrate (33%) in the peritoneal cavity after zymosan. However, anorexia and hypoglycemia were not affected by the lack of IL-1 beta. The induction of corticosterone was only slightly reduced (14%) in IL-1 beta -/- mice. Peritoneal lavage fluid levels for IL-1 alpha, but not for tumor necrosis factor (TNF)-alpha, were also decreased. To evaluate the role of residual IL-1 alpha production in IL-1 beta -/- mice, we used IL-1-receptor antagonist (IL-1ra). In IL-1 beta +/+ mice, IL-1ra inhibited production of IL-6 after zymosan, without affecting TNF-alpha synthesis. There was no further inhibitory effect of IL-1ra on IL-6 production in IL-1 beta -/- mice, suggesting no role for IL-1 alpha in zymosan-induced IL-6. Our results demonstrate that IL-1 beta plays a significant, although not exclusive, role in the physiological and cytokine responses to zymosan-mediated inflammation.