gebhart/patrepeval huggingface dataset:
Do older people who self-harm receive the hospital care they need? (2004)

Although self-harm is most common in younger people in Britain, the risk of suicide subsequent to an initial act of self-harm is considerably greater in older age groups. Four characteristics have been shown to be associated with increased vulnerability in older people who self-harm: increased suicidal intent, physical illness, mental illness and social isolation. This paper is part of a broader analysis of all self-harm presentations to a British hospital accident and emergency department over a five-year period. It examines the prevalence of these vulnerability indicators in patients aged 65 or over, and considers whether greater vulnerability in older patients is reflected in their clinical management within the hospital and in community support planning on discharge.At the first presentation older patients (n=91) exhibited greater vulnerability than did younger patients (n=2,326). Despite this, we found no evidence that older self-harm patients were any more likely than younger patients to routinely receive either a psychosocial assessment from a member of staff with specialist mental health training, or community aftercare planning on discharge from the hospital. This study lends weight to recently published national guidelines recommending that all acts of self-harm in older people be regarded as evidence of serious suicidal intent at the outset.
Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2 (2021)

Following the emergence of SARS-CoV-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. Previous reports described the antiviral activity of certain tyrosine kinase inhibitors (TKIs) targeting the Abelson kinase 2 against pathogenic coronaviruses. Imatinib, one of them, has more than twenty years of safe utilization for the treatment of hematological malignancies. In this context, Imatinib was rapidly evaluated in clinical trials against Covid-19. Here, we present the pre-clinical evaluation of imatinib in multiple models. Our results indicated that imatinib and another TKI, the masitinib, exhibit an antiviral activity in VeroE6 cells. However, imatinib was inactive in a reconstructed bronchial human airway epithelium model. In vivo, imatinib therapy failed to impair SARS-CoV-2 replication in a golden Syrian hamster model despite high concentrations in plasma and in the lung. Overall, these results do not support the use of imatinib and similar TKIs as antivirals in the treatment of Covid-19.
OligoCalc: an online oligonucleotide properties calculator (2007)

We developed OligoCalc as a web-accessible, client-based computational engine for reporting DNA and RNA single-stranded and double-stranded properties, including molecular weight, solution concentration, melting temperature, estimated absorbance coefficients, inter-molecular self-complementarity estimation and intra-molecular hairpin loop formation. OligoCalc has a familiar 'calculator' look and feel, making it readily understandable and usable. OligoCalc incorporates three common methods for calculating oligonucleotide-melting temperatures, including a nearest-neighbor thermodynamic model for melting temperature. Since it first came online in 1997, there have been more than 900,000 accesses of OligoCalc from nearly 200,000 distinct hosts, excluding search engines. OligoCalc is available at http://basic.northwestern.edu/biotools/OligoCalc.html, with links to the full source code, usage patterns and statistics at that link as well.
In Vitro Folding of Escherichia Coli Outer‐Membrane Phospholipase A (1995)

Recombinant outer-membrane phospholipase A (OMPLA) of Escherichia coli was expressed without its signal sequence from the T7 phi 10 promoter. As a result of the cloning strategy the protein had an N-terminal extension of six amino acid residues. The protein accumulated in the cytosol in inclusion bodies. Conditions were established for the efficient folding of OMPLA in vitro in the presence of Triton X-100. After in vitro folding, the protein was present as a mixture of folded and unfolded forms. Ion-exchange chromatography was used for the purification of OMPLA and the separation of correctly folded, enzymically active enzyme from unfolded inactive protein. The final protein preparation was pure and fully heat-modifiable based on SDS/PAGE. The recombinant enzyme had a specific activity of 71 U/mg, which is similar to the value of the wild-type enzyme, purified from the membrane. The final yield of active enzyme was 35 mg protein/l culture of an A600 of 6. Circular dichroism spectroscopy revealed a high content of beta strand, in good agreement with a predicted beta-barrel structure of this outer-membrane protein.
Beta-adrenergic and Muscarinic Modulation of Human Embryonic Stem Cell-derived Cardio-myocytes (2004)

The Micro-Electrode system allows measurement of ionic channel modulation and chronotropic responsiveness in a pharmacological screening setup. Moreover, all our data indicate that cardiomyocytes derived from human embryonic stem cells exhibit a physiological response to the major hormones of the vegetative nervous system and might therefore serve as an ideal candidate for the use in cell replacement strategies.
Mycoplasma fermentans Lipoprotein M161Ag-Induced Cell Activation Is Mediated by Toll-Like Receptor 2: Role of N-Terminal Hydrophobic Portion in its Multiple Functions (2001)

M161Ag is a 43-kDa surface lipoprotein of Mycoplasma fermentans, serving as a potent cytokine inducer for monocytes/macrophages, maturing dendritic cells (DCs), and activating host complement on affected cells. It possesses a unique N-terminal lipo-amino acid, S:-diacylglyceryl cysteine. The 2-kDa macrophage-activating lipopeptide-2 (MALP-2), recently identified as a ligand for Toll-like receptor 2 (TLR2), is derived from M161Ag. In this study, we identified structural motifs sustaining the functions of M161Ag using wild-type and unlipidated rM161Ag with (SP(+)) or without signal peptides (SP(-)). Because the SP(+) rM161Ag formed dimers via 25Cys, we obtained a monomeric form by mutagenesis (SP(+)C25S). Only wild type accelerated maturation of human DCs as determined by the CD83/86 criteria, suggesting the importance of the N-terminal fatty acids for this function. Wild-type and the SP(+) form of monomer induced secretion of TNF-alpha and IL-12 p40 by human monocytes and DCs. Either lipid or signal peptide at the N-terminal portion of monomer was required for expression of this function. In contrast, murine macrophages produced TNF-alpha in response to wild type, but not to any recombinant form of M161Ag, suggesting the species-dependent response to rM161Ag. Wild-type and both monomeric and dimeric SP(+) forms possessed the ability to activate complement via the alternative pathway. Again, the hydrophobic portion was associated with this function. These results, together with the finding that macrophages from TLR2-deficient mice did not produce TNF-alpha in response to M161Ag, infer that the N-terminal hydrophobic structure of M161Ag is important for TLR2-mediated cell activation and complement activation.
Evaluation of "HemoCue," a new device for determining hemoglobin. (1986)

Hemoglobinometry according to the International Committee of Standardization in Hematology (ICSH) suffers from imprecision related to high sample dilution and from potential errors owing to sample turbidity. We have evaluated a new instrument, "HemoCue," that measures hemoglobin at two wavelengths as azide methemoglobin, without dilution. The HemoCue method is superior to the ICSH method: by correction for turbidity, it avoids false hemoglobin readings that may arise from hyperlipemia or some large M-component of the immunoglobulin M class. We find the equipment suitable for use in outpatient units.
Improving robustness to compressed speech in speaker recognition (2013)

The goal of this paper is to analyze the impact of codecdegraded speech on a state-of-the-art speaker recognition system and propose mitigation techniques. Several acoustic features are analyzed, including the standard Mel filterbank cepstral coefficients (MFCC), as well as the noise-robust medium duration modulation cepstrum (MDMC) and power normalized cepstral coefficients (PNCC), to determine whether robustness to noise generalizes to audio compression. Using a speaker recognition system based on i-vectors and probabilistic linear discriminant analysis (PLDA), we compared four PLDA training scenarios. The first involves training PLDA on clean data, the second included additional noisy and reverberant speech, a third introduces transcoded data matched to the evaluation conditions and the fourth, using codec-degraded speech mismatched to the evaluation conditions. We found that robustness to compressed speech was marginally improved by exposing PLDA to noisy and reverberant speech, with little improvement using trancoded speech in PLDA based on codecs mismatched to the evaluation conditions. Noise-robust features offered a degree of robustness to compressed speech while more significant improvements occurred when PLDA had observed the codec matching the evaluation conditions. Finally, we tested i-vector fusion from the different features, which increased overall system performance but did not improve robustness to codec-degraded speech. Index Terms: speaker recognition, speech coding, codec degradation, speaker verification.
The movement of IGF-I into the brain parenchyma after hypoxic-ischaemic injury (1996)

The movement of peptides from CSF into the parenchyma is thought to be slow and diffusion limited. However IGF-I can reduce neuronal loss at distal sites when given centrally 2 h after hypoxic-ischaemic (HI) injury. The present study determined the distribution of [3H]IGF-I given into the lateral ventricle after unilateral HI injury in adult rats. Radioactivity in the injured cortex peaked immediately after administration then rapidly declined. Autoradiography demonstrated radioactivity in the perivascular spaces and in the corpus callosum and external capsule of the injured hemisphere. HPLC and radioimmunoassay confirmed a rise in intracerebral IGF-I levels (from 159 +/- 9 to 401 +/- 88 ng g-1). These data suggest that injury can enhance the movement of IGF-I into the cerebrum via the white matter tracts and perivascular spaces.
Retroviral nucleocapsid proteins possess potent nucleic acid strand renaturation activity (1993)

The nucleocapsid protein (NC) is the major genomic RNA binding protein that plays integral roles in the structure and replication of all animal retroviruses. In this report, select biochemical properties of recombinant Mason-Pfizer monkey virus (MPMV) and HIV-1 NCs are compared. Evidence is presented that two types of saturated Zn2 NC-polynucleotide complexes can be formed under conditions of low [NaCl] that differ in apparent site-size (n = 8 vs. n = 14). The formation of one or the other complex appears dependent on the molar ratio of NC to RNA nucleotide with the putative low site-size mode apparently predominating under conditions of protein excess. Both MPMV and HIV-1 NCs kinetically facilitate the renaturation of two complementary DNA strands, suggesting that this is a general property of retroviral NCs. NC proteins increase the second-order rate constant for renaturation of a 149-bp DNA fragment by more than four orders of magnitude over that obtained in the absence of protein at 37 degrees C. The protein-assisted rate is 100-200-fold faster than that obtained at 68 degrees C, 1 M NaCl, solution conditions considered to be optimal for strand renaturation. Provided that sufficient NC is present to coat all strands, the presence of 400-1,000-fold excess nonhomologous DNA does not greatly affect the reaction rate. The HIV-1 NC-mediated renaturation reaction functions stoichiometrically, requiring a saturated strand of DNA nucleotide:NC ratio of about 7-8, rather than 14. Under conditions of less protein, the rate acceleration is not realized. The finding of significant nucleic acid strand renaturation activity may have important implications for various events of reverse transcription particularly in initiation and cDNA strand transfer.
Optical second-harmonic generation from adsorbate layers in total-reflection geometry (1993)

We study optical second-harmonic generation by a layer of molecules adsorbed on the hypotenuse face of a glass prism, excited from the glass side. We show that second-harmonic generation is particularly effective when the angle of incidence exceeds the critical angle for total reflection. The second-harmonic intensity is calculated as a function of angle of incidence and polarization of the fundamental wave. In total reflection the necessary linear and nonlinear Fresnel factors turn out to be complex valued. We show that rotational intensity patterns, obtained by plotting the second-harmonic intensity as a function of incident polarization angle at fixed angle of incidence, may be used to determine second-order susceptibility components of isotropic adsorbate layers. We verify the theoretical predictions for experimental samples prepared as thin organic films of highly nonlinear hemicyanine dyes by the Langmuir–Blodgett technique.
Effects of elevated temperatures and drugs on the viability of L1210 leukemia cells. (1970)

Summary The lethal action of elevated temperatures on neoplastic cells has been determined quantitatively by means of an in vitro-in vivo system of L1210 leukemia cells. Temperatures from 37° to 40° have little effect on these cells. Prolonged exposure at 41° impairs their viability. Between 41° and 42° the lethal effect increases markedly; in Fischer medium, a 4-log kill is achieved at 42° in 3 hr. The exposure of L1210 leukemia cells to a temperature of 42° for a short time sensitizes them to the action of lower temperatures. A 3-hr exposure at 40° has a highly lethal effect when applied after an initial treatment at 42°. If the sequence of heating is reversed, no such effect is observed. Many drugs have been tested for combined therapy. l-erythro-α,β-Dihydroxybutyraldehyde has been found to act synergistically with heat. dl-Glyceraldehyde, l-phenylalanine mustard, actinomycin D, and sodium oxamate are also active in combination with heat. However, if toxicity to humans is considered, only dl-erythro-α,β-dihydroxybutyraldehyde, dl-glyceraldehyde, and phenylalanine mustard can be considered as suitable for clinical trial in combination with heat.
Characteristics of MuA transposase-catalyzed processing of model transposon end DNA hairpin substrates (2006)

Bacteriophage Mu uses non-replicative transposition for integration into the host's chromosome and replicative transposition for phage propagation. Biochemical and structural comparisons together with evolutionary considerations suggest that the Mu transposition machinery might share functional similarities with machineries of the systems that are known to employ a hairpin intermediate during the catalytic steps of transposition. Model transposon end DNA hairpin substrates were used in a minimal-component in vitro system to study their proficiency to promote Mu transpososome assembly and subsequent MuA-catalyzed chemical reactions leading to the strand transfer product. MuA indeed was able to assemble hairpin substrates into a catalytically competent transpososome, open the hairpin ends and accurately join the opened ends to the target DNA. The hairpin opening and transposon end cleavage reactions had identical metal ion preferences, indicating similar conformations within the catalytic center for these reactions. Hairpin length influenced transpososome assembly as well as catalysis: longer loops were more efficient in these respects. In general, MuA's proficiency to utilize different types of hairpin substrates indicates a certain degree of flexibility within the transposition machinery core. Overall, the results suggest that non-replicative and replicative transposition systems may structurally and evolutionarily be more closely linked than anticipated previously.
Heparin-steroid conjugates: new angiogenesis inhibitors with antitumor activity in mice. (1993)

Inhibitors of angiogenesis hold potential in the treatment of cancer and other diseases where the disease is caused or maintained by the inappropriate growth of blood vessels. In the present study, a novel inhibitor of angiogenesis was synthesized by covalently linking a nonanticoagulating derivative of heparin, heparin adipic hydrazide (HAH), by an acid-labile bond to the antiangiogenic steroid, cortisol. The rationale was that the heparin derivative, which binds to sulfated polyanion receptors on endothelial cells, should concentrate the steroid on the surface of vascular endothelial cells. Endocytosis of the conjugate and decomposition of the acid-labile linkage inside lysosomes and other acidic intracellular compartments should then lead to release of the cortisol and expression of its antiproliferative activity. Analysis of the stability of HAH-cortisol showed that it was stable at pH 7.4 and broke down rapidly (t1/2 15 min) at pH 4.8 at 37 degrees C. Treatment of murine pulmonary capillary endothelial cells with HAH-cortisol at 10(-5) M (with respect to cortisol) suppressed their DNA synthesis by 50% and inhibited their migration into wounded areas of confluent monolayers. HAH-cortisol at 10(-4) M (with respect to cortisol) did not suppress the DNA synthesis of Lewis lung carcinoma cells. Daily i.p. injections of HAH-cortisol into mice bearing s.c. sponge implants retarded vascularization of the sponge, and injections directly into the sponge abolished vascularization for as long as the injections were continued. Daily i.v. injections of HAH-cortisol at doses causing no apparent toxicity retarded the growth of solid s.c. Lewis lung carcinomas in mice by up to 65%. In all of these assays, equivalent treatments with a mixture of the HAH plus cortisol was significantly less effective. The antiproliferative effect of HAH-cortisol on endothelial cells appeared independent of the glucocorticoid activity of the steroid since HAH conjugated to 5 beta-pregnane-3 alpha,17 alpha,21-triol-20-one, a steroid lacking glucocorticoid or mineralocorticoid activity, was even more effective at inhibiting DNA synthesis by murine pulmonary capillary endothelial cells than was HAH-cortisol. In conclusion, HAH-cortisol represents the prototype of a new class of angiogenesis inhibitors for the treatment of cancer and other angiogenic diseases.
Extensive genetic alterations in prostate cancer revealed by dual PCR and FISH analysis (1993)

The genetic alterations that underlie prostate tumorigenesis are assumed to comprise gain or loss of specific chromosomal regions, whole chromosomes, or sequence-specific mutations. Existing data have not demonstrated clear specificity of whole chromosome or regional chromosomal gain or loss that characterizes entire individual malignant lesions, or all malignant lesions, within a cancerous prostate. We have analyzed tissues from 13 patients for target sequences by using PCR and FISH techniques on paired malignant or prostatic intraepithelial neoplastic (PIN) and benign samples (usually from different areas of the same paraffin section). We exercised stringent histologic control over these samples by examining small (< 5 mm2), discrete regions of sectioned benign, malignant, and PIN tissue. The same histologic region was examined on serial sections by FISH and PCR analysis. The tissues were examined for numerical aberrations involving chromosomes 4 (as a control), 7, 8, 10, and the Y by FISH analysis, and for gain or loss of chromosome 7 and chromosomal arms 8p, 10q, and Yp by PCR analysis. The concurrent application of PCR and FISH to microdissected prostatic tissues yielded evidence of higher frequencies of genetic aberration in prostate cancers than those found with either method alone or by other approaches. These results indicate the power of simultaneous genetic assays that are closely linked to specific tumor histology.
Video collections in panoramic contexts (2013)

Video collections of places show contrasts and changes in our world, but current interfaces to video collections make it hard for users to explore these changes. Recent state-of-the-art interfaces attempt to solve this problem for 'outside->in' collections, but cannot connect 'inside->out' collections of the same place which do not visually overlap. We extend the focus+context paradigm to create a video-collections+context interface by embedding videos into a panorama. We build a spatio-temporal index and tools for fast exploration of the space and time of the video collection. We demonstrate the flexibility of our representation with interfaces for desktop and mobile flat displays, and for a spherical display with joypad and tablet controllers. We study with users the effect of our video-collection+context system to spatio-temporal localization tasks, and find significant improvements to accuracy and completion time in visual search tasks compared to existing systems. We measure the usability of our interface with System Usability Scale (SUS) and task-specific questionnaires, and find our system scores higher.
Indications for Heart Transplantation in Pediatric Heart Disease (2007)

This evaluation has led to the development and refinement of indications for heart transplantation for patients with congenital heart disease and pediatric cardiomyopathies in addition to indications for pediatric heart retransplantation.
Cyclopropanation with Diazomethane and Bis(oxazoline)palladium(II) Complexes (1997)

Studies toward the development of an enantioselective diazomethane-based cyclopropanation reagent derived from bis(oxazoline)palladium(II) complexes are reported. Several simple palladium chelates, 2 and 7, in addition to the novel carbon-bound complexes 15 were synthesized and evaluated in the cyclopropanation of various electron-deficient olefins. The X-ray crystal structure of aryl-bis(oxazoline)palladium complex 15c is described. Although all catalysts efficiently affected cyclopropanation, all products were racemic. An intriguing relationship between substitution on the oxazoline ring, particularly the commonly-derivatized 4-position, and catalyst efficiency was discovered. The results are rationalized by either partial or complete bis(oxazoline) decomplexation during the course of the reaction.