gebhart/patrepeval huggingface dataset:
Enhanced external counterpulsation in the management of patients with cardiovascular disease (1999)

Studies over the past several decades support the hypothesis that enhanced external counterpulsation (EECP) can provide long-term benefits in patients with angina secondary to chronic coronary disease. Numerous non-sham controlled trials have recently been substantiated by a multicenter, randomized trial. Although the mechanism by which this mechanical treatment effects an alteration in cellular processes within the myocardium remains unclear, recent scientific investigations suggest that shear stress induced by chronic exposure to EECP might result in the release of a variety of growth factors and the subsequent stimulation of angiogenesis in the coronary beds. Ongoing clinical trials in patients with significant left ventricular dysfunction, an international registry, and additional clinical trials may help to elucidate further the role of this novel and unique therapy in our clinical armamentarium.
Co‐crystals with Acetylene: Small Is not Simple! (2009)

Acetylene is an amazingly versatile component for the formation of co-crystals. It requires careful handling and special techniques for crystallisation, but the efforts seem to be rewarding when attaining co-crystals with small molecules as partners. Many basic questions such as the dominance of specific heterogeneous intermolecular interactions, their driving force for the formation of multicomponent crystals instead of neat ones are expected to be easily analysed. The underlying packing patterns and resulting stoichiometries based on the known supramolecular synthons seem to be straightforward for such small molecules and crystal engineering, considered as the prototype of supramolecular synthesis, should be a simple task. Nineteen co-crystals with acetylene are presented in this paper, some of which have been previously reported individually. An attempt has been made to find features shared by the groups of co-crystals, including those that could not be co-crystallised. But in spite of clear ideas and experiences from previous experiments, surprisingly almost none of systems reached our expectations. Our intuitive approach was not fulfilled, which demonstrates that multicomponent crystals even of small molecules will remain a great challenge for theoretical methods and the crystal structures shown herein represent good candidates for future testing. On the other hand, we wish to encourage other groups to present their views on the crystal structures with an unbiased approach that may offer a better explanation than we are able to outline in this article.
IVHS TECHNOLOGIES APPLIED TO COLLISION AVOIDANCE: PERSPECTIVES ON SIX TARGET CRASH TYPES AND COUNTERMEASURES (1993)

The NHTSA Office of Crash Avoidance Research (OCAR), in conjunction with the Research and Special Programs Administration (RSPA) Volpe National Transportation Systems Center (VNTSC), has underway a multi-disciplinary program to:identify crash causal factors and applicable countermeasure concepts, model target crash scenarios and Intelligent Vehicle Highway System (IVHS) technological interventions, provide preliminary device effectiveness estimates, and to identify countermeasure research data needs. To date, five major target crash types (representing, in the aggregate, more than half of all crashes) have been examined: l Rear-End l Backing l Single Vehicle Roadway Departure (SVRD) l Lane Change/Merge l Signalized Intersection/Crossing Path Independent work is also underway to address the drowsy/fatigued driver problem, an example of a target crash defmed by its cause as opposed to its configuration. This is the sixth crash type described in this paper. This paper presents ...
FOLFOX versus FOLFIRI: a comparison of regimens in the treatment of colorectal cancer metastases. (2005)

Colorectal adenocarcinoma ranks second as a cause of death due to cancer in the Western world. Already at the time of the primary tumor, 15-25% of the patients present with liver metastases while another 20% will develop metastasis following treatment of the colorectal primary. Without any treatment the median survival after the detection of metastases is approximately 9 months, depending on the extent of the disease at the time of diagnosis. Clinical trials with the "FOLFOX and FOLFIRI families" of drugs, designed for the treatment of metastatic colorectal cancer, their results and the costs of each therapy are examined. For each drug, the cost/mg, the cost/mg/m2 and the cost/therapy (according to its duration) are evaluated according to the prices reported in the Italian Directory of Medicines and Manufacturers, 63rd Edition, November 2003.
Use of the chemical cleavage of mismatch method for prenatal deficiency diagnosis of alpha‐1‐antitrypsin (1992)

The most common mutation in alpha-1-antitrypsin deficiency, conversion of a G to an A at base 9989 (PI-Z), was detected with the chemical cleavage of mismatch method, demonstrating the power of the method for prenatal diagnosis. Exon V of the gene was amplified using the polymerase chain reaction and heteroduplexes were formed to test for the presence of the mutation. The predicted C mismatch was readily detectable with hydroxylamine, and by making the probe from the chorionic villus sample it was possible to determine that the fetus was heterozygous, not homozygous, for the mutation.
Isoimmunization against human chorionic gonadotropin with conjugates of processed beta-subunit of the hormone and tetanus toxoid. (1976)

The immunogenicity of the conjugate prepared from "processed" beta-subunit of human chorionic gonadotropin (choriogonadotropin, HCG) and tetanus toxoid has been studied in animals and a human subject. The conjugate elicited the formation of high-affinity (Ka = 10(9)-10(11) M-1) anti-HCG and anti-tetanus antibodies. On primary immunization, the antibody, response lasted for several months. Repeat injection of the conjugate in the declining phase of antibody titers produced a booster response without a lag period. The antibodies reacted with the beta-subunit of HCG and the complete HCG molecule but were devois of significant crossreactivity with human growth hormone, placental lactogen, follicle-stimulating hormone, thyroid-stimulating hormone, and luteinizing hormone at tonic and surge levels. The antibodies were competent for neutralizing the biological activity of HCG in the mouse uterine weight gain assay, the ventral prostate weight gain assay, and the radioligand assay for binding of 125I-labeled HCG to receptors on corpus luteum. HCG (5000 international units) administered to an immunized subject was completely bound by circulating antibodies. Administration of HCG (in contrast to conjugate) was without booster effect on anti-HCG titers.
A Randomized, Double–Blind Trial Comparing Pegylated Interferon Alfa–2B to Interferon Alfa–2B As Initial Treatment for Chronic Hepatitis C (2001)

This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared peginterferon alfa-2b (PegIntron) to interferon alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon alfa-2b dose (3 MIU) or the once-weekly (QW) peginterferon alfa-2b (0.5, 1.0, or 1.5 microg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 peginterferon alfa-2b doses significantly (P < or =.042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 microg/kg peginterferon alfa-2b because of a higher relapse rate among patients treated with 1.5 microg/kg peginterferon alfa-2b, particularly among patients infected with genotype 1. All 3 peginterferon alfa-2b doses decreased liver inflammation to a greater extent than did interferon alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, peginterferon alfa-2b maintained (0.5 microg/kg) or surpassed (1.0, 1.5 microg/kg) the clinical efficacy of interferon alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 microg/kg peginterferon alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation.
Markers of endothelial damage in organ dysfunction and sepsis (2002)

Endothelial activation and damage occur early during sepsis and play a major role in the pathophysiology of systemic inflammation. Various markers of endothelial activation are increased during sepsis and systemic inflammation, and in most studies, the level of markers such as soluble intercellular adhesion molecule, vascular cell adhesion molecule, and E selectin correlate well with the severity of inflammation and the course of the disease. However, to date, it remains unclear whether adhesion molecules and coagulation parameters are superior in this respect to interleukin-6 and procalcitonin, as direct comparisons are lacking. In addition, it is evident that markers of endothelial activation and coagulation parameters lack specificity for infection-induced endothelial damage and organ dysfunction.
Preliminary evaluation of cerebellar stimulation by double-blind stimulation and biological criteria in the treatment of epilepsy (1978)

✓ This series included five patients who had suffered 8 to 23 years of severe, medically intractable seizures without remission, severe socioeconomic handicaps, and an average of over one seizure a day on hospital observation and by history. All had combinations of partial and general seizures with focal and/or bilaterally synchronous epileptiform activity consistently on multiple electroencephalograms (EEG's). One patient had nearly continuous myoclonic activity. Serum levels of phenytoin, primidone, and phenobarbital were adjusted to therapeutic ranges. Three patients had additional medication (diazepam, ethosuximide). Cerebellar biopsy in three patients showed reduction in Purkinje cells. After implantation of cerebellar stimulators, seizure frequency was evaluated in hospital during three or four admissions for 4- to 6-week periods over the ensuing 15 to 21 months. No slow trends toward improvement or deterioration were noted. No significant differences in seizure frequency were found when comparing intervals of about 7 days of on-and-off stimulation both in the double-blind and unblinded conditions. No changes in EEG or Intelligence or Memory Quotients occurred unaccounted for by variations in serum levels of antiepileptic drugs. Despite the lack of objective improvement, patient and family acceptance of cerebellar stimulation was positive to enthusiastic. A rise in CSF norepinephrine and a fall in gamma aminobutyric acid (GABA) accompanied cerebellar stimulation and may be related to the results.
Microarray techniques in pathology: tool or toy? (2000)

Microarray technology allows the simultaneous analysis of up to thousands of different genes in histological or cytological specimens. Although microarray technology has so far mainly been applied in the research setting, its clinical application in pathology is expected in the foreseeable future. This paper presents an overview of the technical "ins and outs" of microarray technology, and discusses several putative applications in diagnostic pathology, which include tumour classification, the prediction of responses to certain chemotherapeutical or hormonal agents, the biological staging of tumours, the risk assessment of premalignant lesions, and the detection of microorganisms.
HEPATIC STELLATE CELLS (2004)

Laboratorio di Epatologia, Dipartimento di Medicina Interna, Università degli Studi di Firenze, Firenze, ITALY
Efficient Synthesis of Taurine and Structurally Diverse Substituted Taurines from Aziridines (2007)

Taurine and substituted taurines were synthesized efficiently from aziridines via ring-opening reaction with thioacetic acid, oxidation with performic acid, and hydrolysis in hydrochloric acid. The current method shows more benefit in purification and efficiency in the preparation of taurine and structurally diverse 2-substituted, 2,2-disubstituted, and 1,2-, 2,2-, and 2,N-alkylene taurines.
Map matching algorithm using interval analysis and Dempster-Shafer theory (2009)

The goal of map matching methods is to compute an accurate position of a vehicle from an initial estimated position using a digital road network data. In this paper, a new map matching method based on Dempster-Shafer theory and interval analysis is presented. The core idea of this method is the use of Dempster-Shafer theory for modeling partial information on model and measurement uncertainties and for managing multiple hypothesis situations. This technique proves to be relevant to treat junction roads situations or parallel roads. The results on simulated data show the usefulness of the proposed method.
MHV-A59 Fusion Mutants Are Attenuated and Display Altered Hepatotropism (1994)

Mouse hepatitis virus strain A59 causes a persistent productive, but nonlytic, infection of cultured glial cells. We have mutants isolated from persistently infected glial cell cultures which have been shown to be fusion-defective due to a histidine to aspartic acid mutation (H716D) near the cleavage site of the peplomer protein, S. Here, we examine the pathogenicity of these mutants and show differences in hepatotropism and virulence compared to wild-type virus (WT). Two mutants chosen for detailed study, B11 and C12, were impaired in their abilities to cause hepatitis and/or replicate in the liver of susceptible mice. Furthermore, B11 and C12 display two separate hepatotropic phenotypes. The ability of B11 to replicate in the liver was dependent on infectious dose and route of inoculation, while C12 consistently displayed decreased hepatotropism regardless of dose and route of inoculation. However, B11 and C12 were shown to replicate in the CNS of infected animals similarly to WT. Like WT, the mutants produced meningoencephalitis during acute infection, with viral antigen exhibiting a similar distribution in the brain, and demyelination during chronic infection. Sequence analysis of wild-type, mutant, and revertant S proteins indicates that (1) a mutation in the N terminal subunit of S (S1), resulting in a glutamine to leucine amino acid substitution (Q159L), may affect hepatotropism and (2) a cleavage site mutation which determines fusogenicity is not responsible for altered hepatotropism. Furthermore, since B11, C12, and a nonattenuated fusion mutant (B12) have identical S protein sequences, there must be additional mutations outside of S which influence both virulence and hepatotropism.
SOME ASPECTS OF ELECTRICAL PROSPECTING APPLIED IN LOCATING OIL STRUCTURES (1932)

Electrical prospecting is defined as the science and the art of determining the variations of the electrical constants (resistivity, magnetic permeability and the dielectric constant) of the earth's crust and of interpreting these variations in terms of geological structure. The most successful systems of prospecting are based on the study of resistivity variations. The basic assumption made is that in general changes of resistivity follow the bedding planes. Electrical methods of exploration may be divided into two classes, direct current methods and alternating current methods. In part II the fundamental theory of direct current method is discussed and a typical survey is described. Part III deals with the theory of alternating current methods, with particular reference to the optimum frequency to be used. It is shown that in general very low frequencies are desirable. Two alternating current surveys made by the Swedish American Prospecting Corporation are briefly described. In the conclusion (part IV) some of the difficulties of electrical prospecting are discussed. The depth to which investigations may be carried is limited. In the present stage of the art, it would take exceptionally favorable conditions to obtain reliable information much in excess of 2,000 feet. However, it is stated that improvements in methods of interpretation and in field technique should give electrical methods a definite field of usefulness in prospecting for oil.
Identification and Characterization of Small Molecule Inhibitors of the Calcium-Dependent S100B−p53 Tumor Suppressor Interaction (2004)

The binding of S100B to p53 down-regulates wild-type p53 tumor suppressor activity in cancer cells such as malignant melanoma, so a search for small molecules that bind S100B and prevent S100B−p53 complex formation was undertaken. Chemical databases were computationally searched for potential inhibitors of S100B, and 60 compounds were selected for testing on the basis of energy scoring, commercial availability, and chemical similarity clustering. Seven of these compounds bound to S100B as determined by steady state fluorescence spectroscopy (1.0 μM ≤ KD ≤ 120 μM) and five inhibited the growth of primary malignant melanoma cells (C8146A) at comparable concentrations (1.0 μM ≤ IC50 ≤ 50 μM). Additionally, saturation transfer difference (STD) NMR experiments confirmed binding and qualitatively identified protons from the small molecule at the small molecule−S100B interface. Heteronuclear single quantum coherence (HSQC) NMR titrations indicate that these compounds interact with the p53 binding site on S100B. An NMR-docked model of one such inhibitor, pentamidine, bound to Ca2+-loaded S100B was calculated using intermolecular NOE data between S100B and the drug, and indicates that pentamidine binds into the p53 binding site on S100B defined by helices 3 and 4 and loop 2 (termed the hinge region).
A Simplified Procedure for Purification of Human Prothrombin, Factor IX and Factor X (1981)

A simplified procedure is described for the purification of prothrombin, Factor X and Factor IX in overall yields of 35-40% from pooled human plasma. The initial steps, which are common to prior purification techniques, include adsorption onto and elution from barium citrate, ammonium sulfate fractionation, and DEAE-Sephadex chromatography. The procedure differs from previous techniques in that the nest step, heparin-agarose chromatography, is carried out in a (sodium) citrate buffer, pH 7.5. These chromatographic conditions permit the separation of prothrombin, Factor X and Factor IX from each other, yielding fractions with apparent homogeneity in several electrophoretic systems. The additional chromatographic steps of earlier purification procedures are therefore unnecessary. The heaprin-agrarose column chromatographic conditions consistently resulted in the separation of human prothrombin in into two fractions in a ratio of approximately 4:1. Both fractions possess similar specific activity in a one stage prothrombin assay, and also activate at the same rate in a Factor Xa, Ca2+ and phospholipid system. Both fractions of prothrombin also comigrate in sodium dodecyl sulfate gel electrophoresis with an apparent Mr integral of 70,000.
Silver catalysis in the fabrication of silicon nanowire arrays (2006)

A method involving dry deposition plus wet chemical etching was devised to fabricate silicon nanowire (SiNW) arrays and to study silver catalysis during fabrication. Through investigation of the track of catalyst particles, it was shown that Ag really catalyses the etching of silicon underneath Ag, which clarifies doubts about the formation of SiNW arrays during wet chemical etching. The intrinsic properties of Ag and the network structure of Ag clusters during etching facilitate the etching process. The etching product, i.e. vertical SiNW arrays containing an Ag nanocluster mesh, could be considered as a prototype secondary composite nanostructured catalyst with promise for future applications.
Immunotoxins containing Pseudomonas exotoxin that target LeY damage human endothelial cells in an antibody-specific mode: relevance to vascular leak syndrome. (1995)

Vascular leak syndrome (VLS) was originally found to be a major dose-limiting toxicity in humans with cancer treated with several immunotoxins (ITs) containing ricin A chain or blocked ricin. Recently, VLS has also been observed in patients treated with an IT containing the murine monoclonal antibody (MAb) B3 coupled to LysPE38, a recombinant truncated form of Pseudomonas exotoxin (PE) A. Antibody B3 (IgG1k) recognizes LewisY and related carbohydrate epitopes present on many human solid tumors, and B3-LysPE38 showed excellent antitumor activity in nude mice bearing tumors that express the B3 antigen. In the clinical trial, the development of VLS has prevented the administration of the amount of IT necessary to achieve blood levels required for good therapeutic responses. We have now investigated the effects of several PE-based ITs on different human endothelial cell lines to elucidate the mechanism of VLS induced by ITs containing PE. To assess the cytotoxic effect of IT on endothelial cells, various ITs were incubated with cells for 2 or 20 h, and the incorporation of [3H]leucine into protein was measured. The endothelial cells studied were human umbilical vein endothelial cells, human lung-derived microvascular endothelial cells (HUVECs), human adult dermal microvascular endothelial cells, human pulmonary artery endothelial cells, and human aortic endothelial cells. We found that both B3-LysPE38 (LMB-1), a chemical conjugate of MAb B3 with PE38, as well as B3(Fv)-PE38 (LMB-7), a recombinant single chain immunotoxin, inhibited protein synthesis, with 50% inhibitory concentrations between 600 and 1000 ng/ml for 20-h incubation in HUVECs, human lung-derived microvascular endothelial cells, and human adult dermal microvascular endothelial cells but not on human pulmonary artery endothelial cells. The cytotoxic effect was specific since PE38 itself or PE coupled to several other antibodies did not inhibit protein synthesis in these cells even at 10,000 ng/ml. Further evidence that the cytotoxicity of B3-containing ITs is due to specific B3 binding to endothelial cells comes from the fact that the cytotoxicity can be blocked by excess free MAb B3. HUVECs undergo overt morphological changes after treatment with B3-LysPE38 or B3(Fv)PE38. Gaps between the cells are formed after a 20-h exposure but not after 2 h. These studies suggest that VLS in patients is due to capillary damage caused by prolonged exposure to high concentrations of LMB-1.
Design of a Highly Effective Therapeutic HPV16 E6/E7-Specific DNA Vaccine: Optimization by Different Ways of Sequence Rearrangements (Shuffling) (2014)

Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.