gebhart/patrepeval huggingface dataset:
Construction of a recombinant human parvovirus B19: adeno-associated virus 2 (AAV) DNA inverted terminal repeats are functional in an AAV-B19 hybrid virus. (1989)

To facilitate genetic analysis of the human pathogenic parvovirus B19, we constructed a hybrid B19 viral genome in which the defective B19 inverted terminal repeats were replaced with the full-length inverted terminal repeats from a nonpathogenic human parvovirus, the adeno-associated virus 2 (AAV). The hybrid AAV-B19 genome was rescued from a recombinant plasmid and then the DNA was replicated upon transfection into adenovirus 2-infected human KB cells in the presence of AAV genes coding for proteins required for AAV DNA replication (AAV-Rep proteins). In addition, in the presence of AAV genes coding for the viral capsid proteins (AAV-Cap proteins), the rescued/replicated hybrid AAV-B19 genomes were packed into mature AAV progeny virions, which were subsequently released into culture supernatants. The recombinant AAV-B19 progeny virions were infectious for normal human bone marrow cells and strongly suppressed erythropoiesis in vitro. The availability of an infectious recombinant B19 virus should facilitate the mutational analysis of the viral genome, which, in turn, may yield information on individual viral gene functions in B19-induced pathogenesis. The hybrid AAV-B19 genome may also prove to be a useful vector for gene transfer in human bone marrow cells.
Groucho running (1987)

An important determinant of the mechanics of running is the effective vertical stiffness of the body. This stiffness increases with running speed. At any one speed, the stiffness may be reduced in a controlled fashion by running with the knees bent more than usual. In a series of experiments, subjects ran in both normal and flexed postures on a treadmill. In other experiments, they ran down a runway and over a force platform. Results show that running with the knees bent reduces the effective vertical stiffness and diminishes the transmission of mechanical shock from the foot to the skull but requires an increase of as much as 50% in the rate of O2 consumption. A new dimensionless parameter (u omega 0/g) is introduced to distinguish between hard and soft running modes. Here, omega 0 is the natural frequency of a mass-spring system representing the body, g is gravity, and u is the vertical landing velocity. In normal running, this parameter is near unity, but in deep-flexed running, where the aerial phase of the stride cycle almost disappears, u omega 0/g approaches zero.
The Origin of the Haitian Cholera Outbreak Strain (2010)

The Haitian epidemic is probably the result of the introduction, through human activity, of a V. cholerae strain from a distant geographic source. (Funded by the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute.).
β(1,2)-Xylose and α(1,3)-Fucose Residues Have a Strong Contribution in IgE Binding to Plant Glycoallergens (2000)

Primary structures of the N-glycans of two major pollen allergens (Lol p 11 and Ole e 1) and a major peanut allergen (Ara h 1) were determined. Ole e 1 and Ara h 1 carried high mannose and complex N-glycans, whereas Lol p 11 carried only the complex. The complex structures all had a beta(1,2)-xylose linked to the core mannose. Substitution of the proximal N-acetylglucosamine with an alpha(1, 3)-fucose was observed on Lol p 11 and a minor fraction of Ole e 1 but not on Ara h 1. To elucidate the structural basis for IgE recognition of plant N-glycans, radioallergosorbent test analysis with protease digests of the three allergens and a panel of glycoproteins with known N-glycan structures was performed. It was demonstrated that both alpha(1,3)-fucose and beta(1,2)-xylose are involved in IgE binding. Surprisingly, xylose-specific IgE antibodies that bound to Lol p 11 and bromelain did not recognize closely related xylose-containing structures on horseradish peroxidase, phytohemeagglutinin, Ole e 1, and Ara h 1. On Lol p 11 and bromelain, the core beta-mannose is substituted with just an alpha(1,6)-mannose. On the other xylose-containing N-glycans, an additional alpha(1,3)-mannose is present. These observations indicate that IgE binding to xylose is sterically hampered by the presence of an alpha(1,3)-antenna.
Improved nucleotide selectivity and termination of 3′-OH unblocked reversible terminators by molecular tuning of 2-nitrobenzyl alkylated HOMedU triphosphates (2011)

We describe a novel 3'-OH unblocked reversible terminator with the potential to improve accuracy and read-lengths in next-generation sequencing (NGS) technologies. This terminator is based on 5-hydroxymethyl-2'-deoxyuridine triphosphate (HOMedUTP), a hypermodified nucleotide found naturally in the genomes of numerous bacteriophages and lower eukaryotes. A series of 5-(2-nitrobenzyloxy)methyl-dUTP analogs (dU.I-dU.V) were synthesized based on our previous work with photochemically cleavable terminators. These 2-nitrobenzyl alkylated HOMedUTP analogs were characterized with respect to incorporation, single-base termination, nucleotide selectivity and photochemical cleavage properties. Substitution at the α-methylene carbon of 2-nitrobenzyl with alkyl groups of increasing size was discovered as a key structural feature that provided for the molecular tuning of enzymatic properties such as single-base termination and improved nucleotide selectivity over that of natural nucleotides. 5-[(S)-α-tert-Butyl-2-nitrobenzyloxy]methyl-dUTP (dU.V) was identified as an efficient reversible terminator, whereby, sequencing feasibility was demonstrated in a cyclic reversible termination (CRT) experiment using a homopolymer repeat of ten complementary template bases without detectable UV damage during photochemical cleavage steps. These results validate our overall strategy of creating 3'-OH unblocked reversible terminator reagents that, upon photochemical cleavage, transform back into a natural state. Modified nucleotides based on 5-hydroxymethyl-pyrimidines and 7-deaza-7-hydroxymethyl-purines lay the foundation for development of a complete set of four reversible terminators for application in NGS technologies.
Spectral mapping of the electrocardiogram with Fourier transform for identification of patients with sustained ventricular tachycardia and coronary artery disease (1989)

In time domain analysis, detection of late potentials is limited by high pass filtering, noise interference and the necessity to exclude patients with bundle branch block. We therefore used frequency analysis with Fourier transform of multiple segments of the surface electrocardiogram (25 segments, size 80 ms, time shift 3 ms) during sinus rhythm after signal averaging. Thirty-two post-myocardial infarction patients with sustained ventricular tachycardia (VT), 19 post-myocardial infarction patients without VT and 17 healthy subjects were studied. A total of 18 patients had bundle branch block. In 24 out of 32 patients with VT, three-dimensional spectral plots were characterized by spectral peaks greater than 10 dB in the range of 40-200 Hz in segments only at the end of QRS and the early ST wave, but not far outside the QRS. In only 2 out of 19 patients without VT and in 1 out of 17 healthy subjects could such peaks be observed. Noise caused spectral peaks throughout all segments. Sixteen out of 18 patients with bundle branch block were correctly classified with spectral mapping. With the Simson method, patients with bundle branch block had to be excluded, abnormal results were found in 10 out of 19 patients with VT, but also in 5 out of 15 patients without VT and in 3 out of 16 healthy subjects. Thus, spectral mapping of the electrocardiogram offers promise for better identification of patients prone to sustained VT in the presence of coronary artery disease.
Can we measure wave aberration in patients with diffractive IOLs? (2007)

Journal of Cataract & Refractive Surgery 33(11):p 1997, November 2007. | DOI: 10.1016/j.jcrs.2007.06.052
Biodegradable Thermoresponsive Hydrogels for Aqueous Encapsulation and Controlled Release of Hydrophilic Model Drugs (2005)

A series of hydrogels with both thermoresponsive and completely biodegradable properties was developed for aqueous encapsulation and controlled release of hydrophilic drugs in response to temperature change. The hydrogels were prepared in phosphate-buffered saline (pH 7.4) through free radical polymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-2-hydroxyethyl methacrylate units (Dex-lactateHEMA). Swelling measurement results demonstrated that four gels with feeding weight ratios of NIPAAm:Dex-lactateHEMA = 7:2, 6:3, 5:4, and 4:5 (w/w) were thermoresponsive by showing a lower critical solution temperature at approximately 32 degrees C. The swelling and degradation of the hydrogels strongly depended on temperature and hydrogel composition. An empirical mathematical model was established to describe the fast water absorption at the early stage and deswelling at the late stage of the hydrogels at 37 degrees C. Two hydrophilic model drugs, methylene blue and bovine serum albumin, were loaded into the hydrogels during the synthesis process. The molecular size of the drugs, the hydrophilicity and degradation of the hydrogels, and temperature played important roles in controlling the drug release.
Glucose, but not glutamine, protects against spontaneous and anti-Fas antibody-induced apoptosis in human neutrophils (2002)

Neutrophils are phagocytic cells of the innate immune system that use a combination of reactive oxygen species and anti-microbial toxins to kill and destroy ingested micro-organisms. Once they have performed their function, neutrophils die by apoptosis, which is important for the effective resolution of the inflammatory response. Both glucose and glutamine are important fuels for neutrophils, yet little has been done to investigate the comparative effects of glucose and glutamine on neutrophil apoptosis. We hypothesized that glucose and/or glutamine significantly alter rates of spontaneous and anti-Fas antibody-induced apoptosis of human neutrophils cultured ex vivo. Neutrophil apoptosis was reduced by increasing the extracellular concentration of glucose, but was unaffected by glutamine concentration. The protective effect of glucose appeared to correlate with the rate of glucose utilization. The addition of a competitive inhibitor of glycolysis, 2-deoxy-D-glucose (10 mM), attenuated the protective effect of 5.5 mM glucose, indicating that glucose metabolism is essential for its protective effect against apoptosis. There was a significant (P<0.05) reduction in the intracellular ATP concentration of neutrophils incubated in the absence of extracellular glucose compared with cells incubated in the presence of 5.5 mM glucose. The protective effect of glucose against apoptosis may be mediated by maintenance of the intracellular ATP concentration.
Defensin‐6 mRNA in human Paneth cells: implications for antimicrobia peptides in host defense of the human bowel (1993)

The epithelial surface of the human small intestine is a barrier between the host and the microbial environment of the lumen. A human small intestine cDNA clone was found to encode a new member of the defensin family of antimicrobial peptides, named human defensin-6. Tissue expression of this mRNA is specific for the small intestine as determined by Northern blot analysis and polymerase chain reaction analysis. In situ hybridization demonstrated that human defensin-6 mRNA localizes to Paneth cells in the crypts of Lieberkühn. The finding of an abundant defensin mRNA in human Paneth cells supports the notion that these epithelial cells may play a key role in host defense of the human bowel. The results also strengthen the hypothesis that peptide-based host defenses are prevalent at mucosal surfaces in mammals.
A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer (2006)

The development of acquired resistance to ErbB2 tyrosine kinase inhibitors limits the clinical efficacy of this class of cancer therapeutics. Little is known about the mechanism(s) of acquired resistance to these agents. Here we establish a model of acquired resistance to N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2 (methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (lapatinib), an inhibitor of ErbB2 and ErbB1 tyrosine kinases by chronically exposing lapatinib-sensitive ErbB2-overexpressing breast cancer cells to lapatinib, simulating the clinic where lapatinib is administered on a daily chronic basis. Analysis of baseline gene expression in acquired lapatinib-resistant and parental cells indicates estrogen receptor (ER) signaling involvement in the development of resistance. Using gene interference, we confirm that acquired resistance to lapatinib is mediated by a switch in cell survival dependence and regulation of a key antiapoptotic mediator from ErbB2 alone to codependence upon ER and ErbB2 rather than loss of ErbB2 expression or insensitivity of ErbB2 signaling to lapatinib. Increased ER signaling in response to lapatinib is enhanced by the activation of factors facilitating the transcriptional activity of ER, notably FOXO3a and caveolin-1. Importantly, we confirm that lapatinib induces ER signaling in tumor biopsies from patients with ErbB2-overexpressing breast cancers receiving lapatinib therapy. These findings provided the rationale for preventing the development of acquired resistance by simultaneously inhibiting both ER and ErbB2 signaling pathways. Establishing clinically relevant models of acquired resistance to ErbB2 kinase inhibitors will enhance therapeutic strategies to improve clinical outcomes for patients with ErbB2-overexpressing breast cancers.
Touchalytics: On the Applicability of Touchscreen Input as a Behavioral Biometric for Continuous Authentication (2012)

We investigate whether a classifier can continuously authenticate users based on the way they interact with the touchscreen of a smart phone. We propose a set of 30 behavioral touch features that can be extracted from raw touchscreen logs and demonstrate that different users populate distinct subspaces of this feature space. In a systematic experiment designed to test how this behavioral pattern exhibits consistency over time, we collected touch data from users interacting with a smart phone using basic navigation maneuvers, i.e., up–down and left–right scrolling. We propose a classification framework that learns the touch behavior of a user during an enrollment phase and is able to accept or reject the current user by monitoring interaction with the touch screen. The classifier achieves a median equal error rate of 0% for intrasession authentication, 2%–3% for intersession authentication, and below 4% when the authentication test was carried out one week after the enrollment phase. While our experimental findings disqualify this method as a standalone authentication mechanism for long-term authentication, it could be implemented as a means to extend screen-lock time or as a part of a multimodal biometric authentication system.
Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes. (1995)

We have used differential display PCR to search for mRNAs induced by delta Raf-1:ER, an estradiol-dependent form of Raf-1 kinase. Through this approach the gene encoding heparin-binding epidermal growth factor (HB-EGF) was identified as an immediate-early transcriptional target of oncogenic Raf kinases. Activation of delta Raf-1:ER and a conditional oncogenic form of B-Raf, delta B-RAF:ER, resulted in rapid and sustained induction of HB-EGF mRNA expression and secretion of mature HB-EGF from cells. Neutralizing anti-HB-EGF antisera prevented the delayed activation of the c-Jun amino-terminal kinases that is observed in cells transformed by delta Raf-1:ER. These results demonstrate that distinct signaling pathways can cross talk via the secretion of polypeptide growth factors. Furthermore, cells transformed by oncogenic Ras, which also induced HB-EGF expression, demonstrated a marked increase in sensitivity to the cytotoxic action of diphtheria toxin, for which the membrane anchored HB-EGF precursor acts as a cell-surface receptor.
Organ Shortage: The Greatest Challenge Facing Transplant Medicine (2014)

The success of organ transplantation as a treatment for end-stage organ disease has yielded a series of ethical quandaries originating from the issue of organ shortage. Scarcity of organs for transplantation necessitates formulation of just and fair allocation policies as well as ethically viable solutions to bridging the vast gap between organ supply and demand. The concept of "triage" provides a useful paradigm in which to contextualize the organ shortage issue. This entails subjugating the welfare of the individual patient for the benefit of the wider community as an ethically justified response to the challenge of scarcity.
Spontaneously organized molecular assemblies. 1. Formation, dynamics, and physical properties of n-alkanoic acids adsorbed from solution on an oxidized aluminum surface (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpontaneously organized molecular assemblies. 1. Formation, dynamics, and physical properties of n-alkanoic acids adsorbed from solution on an oxidized aluminum surfaceDavid L. Allara and Ralph G. NuzzoCite this: Langmuir 1985, 1, 1, 45–52Publication Date (Print):January 1, 1985Publication History Published online1 May 2002Published inissue 1 January 1985https://pubs.acs.org/doi/10.1021/la00061a007https://doi.org/10.1021/la00061a007research-articleACS PublicationsRequest reuse permissionsArticle Views3715Altmetric-Citations590LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
EFFECTS OF THE BRADYKININ B2 RECEPTOR ANTAGONIST ICATIBANT ON MICROVASCULAR PERMEABILITY AFTER THERMAL INJURY IN SHEEP (2007)

Peptide kinins are potent vasoactive agents in the microcirculation that might be released after burn injury. The present study was designed to test the hypothesis that Icatibant (JE 049), a potent, selective peptidomimetic bradykinin-B2 receptor antagonist, would reduce the cardiovascular pathology occurring in sheep exposed to 40% total body surface area (TBSA), third-degree burn. Female sheep were surgically prepared for chronic study. After 5 to 7 days' recovery from the operative procedure, they were randomized to five groups: sham (n = 6, noninjured, nontreated), medicated sham (n = 4, noninjured, treated with 20 microg kg h Icatibant), control (n = 7, 40% TBSA third-degree burn, nontreated), Icatibant-4 (n = 6, 40% TBSA third-degree burn, treated with 4 microg kg h Icatibant [low dose]), Icatibant-20 (n = 8, 40% TBSA third-degree burn, treated with 20 microg kg h Icatibant [high dose]). Prefemoral lymph flow (milliliters per hour) remained constant in the sham and medicated sham groups but increased after injury: control (0 h, 3.9 +/- 0.5; 24 h, 28 +/- 4.2; 48 h, 33.0 +/- 8.1). The increased fluid flux was associated with enhanced protein flux. Both low and high doses of Icatibant significantly reduced the microvascular fluid flux: Icatibant-4 (0 h, 5.3 +/- 0.6; 24 h, 17.5 +/- 3.5; 48 h, 20.3 +/- 3.4); Icatibant-20 (0 h, 5.3 +/- 1.1; 24 h, 15.2 +/- 2; 48 h, 17.6 +/- 4.1). Total prefemoral protein leak was reduced in all treatment groups. The low dose of Icatibant significantly reduced prefemoral lymph flow without adversely affecting the hemodynamic changes observed after burn injury in sheep, suggesting that the bradykinin antagonist would reduce edema formation and improve fluid management of thermally injured patients.
TFAP2A Regulates Nasopharyngeal Carcinoma Growth and Survival by Targeting HIF-1α Signaling Pathway (2013)

TFAP2A is a transcription factor that orchestrates a variety of cell processes, including cell growth and tissue differentiation. However, the regulation of TFAP2A in human nasopharyngeal carcinoma tumorigenesis and its precise mechanism of action remain largely unknown. In this study, we investigated the biologic role and clinical significance of TFAP2A in nasopharyngeal carcinoma growth and progression and identified the underlying molecular mechanisms. We found that TFAP2A was highly expressed in various nasopharyngeal carcinoma cell lines and tumor tissue specimens and was significantly correlated with hypoxia-inducible factor-1α (HIF-1α) expression. A positive correlation of TFAP2A overexpression with advanced tumor stage, local invasion, clinical progression, and poor prognosis of patients with nasopharyngeal carcinomas were also observed. Moreover, we found that knockdown of TFAP2A expression by siRNA significantly inhibited tumor cell growth in nasopharyngeal carcinoma cell lines and in a subcutaneous xenograft mouse model by targeting the HIF-1α-mediated VEGF/pigment epithelium-derived factor (PEDF) signaling pathway. Treatment of nasopharyngeal carcinoma cells with TFAP2A siRNA dramatically inhibited the expression and the release of VEGF protein but did not change the level of PEDF protein, resulting in a significant reduction of the ratio of VEGF/PEDF. Pretreatment with a HIF-1α siRNA did not significantly change the TFAP2A siRNA-mediated inhibition in cell viability. Our results indicate that TFAP2A regulates nasopharyngeal carcinoma growth and survival through the modulation of the HIF-1α-mediated VEGF/PEDF signaling pathway, and suggest that TFAP2A could be a potential prognostic biomarker and therapeutic target for nasopharyngeal carcinoma treatment.
Retinoic Acid Inhibits β-Catenin through Suppression of Cox-2 (2007)

Mutations in adenomatous polyposis coli (APC) underlie the earliest stages of colorectal carcinogenesis. Consequences of APC mutation include stabilization of beta-catenin, dysregulation of cyclooxygenase-2 (COX-2) expression, and loss of retinoic acid production, events with poorly defined interactions. Here we showed that treatment of zebrafish expressing a truncated form of Apc with either retinoic acid or a selective COX-2 inhibitor decreased beta-catenin protein levels and downstream signaling events. Interestingly, the destruction of beta-catenin in apc mutant embryos following Cox-2 inhibition required the presence of truncated Apc. These findings support roles for retinoic acid and Cox-2 in regulating the stability of beta-catenin following Apc loss. Furthermore, truncated Apc appears to retain the ability to target beta-catenin for destruction, but only in the absence of Cox-2 activity. This novel function of truncated Apc may provide a molecular basis for the efficacy of COX-2 inhibitors in the treatment of colon cancer.