gebhart/patrepeval huggingface dataset:
Covalent DNA Damage in Tissues of Cigarette Smokers as Determined by 32P-Postlabeling Assay (1989)

Covalent DNA addition products (adducts) formed by the reaction of chemical carcinogens or their metabolites with DNA are critically involved in the initiation of chemical carcinogenesis and may serve as molecular markers and dosimeters for environmental carcinogen exposures. Using a highly sensitive 32P-postlabeling assay for DNA adduct analysis, we studied DNA damage elicited by cigarette smoke in tissues of smokers. A multitude of characteristic smoking-induced, presumably aromatic DNA adducts were found to occur in a dose- and time-dependent manner in the lung, bronchus, and larynx of smokers with cancer of these organs and to decline only slowly after cessation of smoking. Low levels of adducts appeared to persist for up to 14 years in the lungs of exsmokers with high previous exposures. These results corroborate data of epidemiological studies showing that the lung cancer risk and mortality of smokers increase with the intensity and duration of smoking and decline only slowly after cessation of smoking. Tissue distribution studies in autopsy samples revealed the presence of smoking-associated DNA lesions also in the kidney, bladder, esophagus, heart, ascending aorta, and liver. The most extensive DNA damage was found in lung and heart, i.e., 1 aromatic adduct in about 10(7) DNA nucleotides. Our results suggest that cigarette smoking-induced DNA adduct formation is causally related to cancer in the target organs.
Time-dose-fractionation in radioimmunotherapy: implications for selecting radionuclides. (1993)

As currently practiced, the doses delivered to tumors in radioimmunotherapy are less than desirable primarily because of dose-limiting bone marrow toxicity, thus reducing the therapeutic efficacy of this modality. The biological effectiveness of internal radionuclide therapy depends on the total dose, the rate at which it is delivered, and the fractionation schedule of the radiolabeled antibodies administered. A new approach, based on time-dose-fractionation (TDF), which has been used in conventional radiotherapy, is advanced. This approach incorporates differences in dose rates, biological half-lives of the antibodies, physical half-lives of the radionuclides employed and the total doses needed for a given biological effect. The TDF concept is illustrated with several relevant examples for radioimmunotherapy. Based on the TDF approach, it is proposed that under certain biological conditions radionuclides with physical half-lives that are 1-3 times the biological half-life of the radiolabeled antibodies in the tumor are more likely to deliver sterilization doses to tumors than the shorter-lived nuclides presently in use unless precluded by specific activity considerations. Several radionuclides that meet this criteria are suggested with 32P being the most promising among them. Finally, a practical method for treatment planning in radioimmunotherapy using TDF factors is recommended.
Exploration of Ionic Liquids as Soluble Supports for Organic Synthesis. Demonstration with a Suzuki Coupling Reaction (2003)

The efficiency of ionic liquid supported synthesis was demonstrated by the Suzuki reaction of ionic liquid supported iodobenzoate compounds with arylboronic acids in aqueous media to give, after cleavage with ammonia/methanol, biaryl products in good yields and high purities, without the need for chromatographic purification. [reaction: see text]
Haemodynamics and plasma concentrations following sublingual GTN and intravenous, or inhaled, isosorbide dinitrate. (1984)

We measured plasma nitrate levels and haemodynamics following sublingual glyceryl trinitrate (GTN) (0.5 mg), or isosorbide dinitrate (ISDN) administered intravenously (0.5 mg) or by inhalation (1.25 mg) in 23 patients undergoing cardiac catheterisation for investigation of chest pain. Peak levels were detected at 90 s and 5 min following intravenous and inhaled ISDN respectively and at 3 min following sublingual GTN. Intravenous and inhaled ISDN produced similar plasma levels at 30 s and both were significantly greater than following sublingual GTN. Plasma levels were maintained for longer following inhaled ISDN than intravenous ISDN or sublingual GTN. Haemodynamic responses were qualitatively similar following each treatment; reduction in pulmonary vascular resistance and pressure and left ventricular end diastolic pressure occurred in each group. Heart rate, cardiac output and LV dP/dt.P-1 remained unchanged. Maximal haemodynamic responses were greater following ISDN than GTN, with little difference between the two preparations of ISDN. Haemodynamic responses were more sustained following inhaled ISDN than following sublingual GTN or intravenous ISDN, the latter two being similar in this respect. These findings suggest that inhaled ISDN may provide more rapid and sustained relief from angina than sublingual GTN.
Electro-optic properties of thiol-ene polymer stabilized ferroelectric liquid crystals (2003)

Abstract Electro-optic properties of polymer stabilized ferroelectric liquid crystal (PSFLC) systems are examined as a function of varying concentrations of either a linear or crosslinked thiol-ene polymer. The thiol-ene method of polymer stabilization is a drastic change from previous studies designed to avert the problem of polymer phase separation. FLC rise time and tilt angle measurements were used to determine the effects of the polymer network on the optical properties of the system. The addition of monomer impurities to both systems demonstrated a reduction in tilt angle, which translated into decreased switching speeds in both systems prior to polymerization. The crosslinked thiol-ene system showed increased switching times due to the creation of polymer in the interlayer spacing of the FLC, but exhibited minimal increase in the rotational viscosity of the system. In addition, the crosslinked polymer systems resulted in an increase in the liquid crystalline order, which produced an increase in the contrast ratio of the system. The linear polymer system showed drastically different results as compared with the crosslinked system. The rise time and tilt angle measurements decreased upon polymerization of the linear thiol-ene and the rotational viscosity and contrast ratio values also decreased. We suggest that the linear thiol-ene polymer phase separation from the interlayer spacing leads to a microscopic misalignment of the FLC molecules, causing a decrease in the optical properties of the LC.
Intratumoral distribution of radiolabeled antibody and radioimmunotherapy in experimental liver metastases model of nude mouse. (1999)

Liver metastases had easy accessibility to the antibody. Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral distribution of injected antibody and were successfully treated with 131I-labeled antibody. Very high uptake and satisfactory metastasis-to-liver ratios with 111In-labeled antibody suggest that the use of a radiometal with high beta-energy, such as 90Y or 188Re, is preferable for the successful radioimmunotherapy of metastases larger than 1 mm.
Entropy Estimates from Insufficient Samplings (2003)

We present a detailed derivation of some estimators of Shannon entropy for discrete distributions. They hold for finite samples of N points distributed into M "boxes", with N and M -&gt; oo, but N/M &lt; oo. In the high sampling regime (&lt;&lt; 1 points in each box) they have exponentially small biases. In the low sampling regime the errors increase but are still much smaller than for most other estimators. One advantage is that our main estimators are given analytically, with explicitly known analytical formulas for the biases.
Transition-metal catalyzed synthesis of Ketoprofen (2000)

Transition metal-catalyzed reactions including carbonylations, hydrovinylations and hydrogenations have been applied in the synthesis of alpha-(3-benzoylphenyl)propanoic acid (Ketoprofen). 3-Vinylbenzophenone was obtained from 3-bromobenzophenone by a Pd-catalyzed Heck coupling reaction. Pd-catalyzed carbonylation of this olefin gave the isopropyl alpha-(3-benzoylphenyl) propionate in high yield (95%) and with high regioselectivity (>99.5%). Ketoprofen was obtained in 90% yield by hydrolysis of the isopropyl ester. It was also obtained in two steps from 3-vinylbenzophenone by a Ni-catalyzed hydrovinylation selectively affording 3-(3'-benzoylphenyl)-1-butene, followed by an oxidation. 3-Ethynylbenzophenone was obtained from 3-bromobenzophenone by Pd-catalyzed coupling reaction. By means of a Pd-catalyzed carbonylation, this alkyne was converted regioselectively (97%) into methyl alpha-(3-benzoylphenyl) acrylate (93% yield). Hydrolysis of the ester afforded the alpha-(3-benzoylphenyl)acrylic acid. Asymmetric hydrogenation of this acid to give (S)-ketoprofen in 95% optical yield was achieved using a chiral Ru-(S)-BINAP catalyst.
Imaging of lipid species by MALDI mass spectrometry (2008)

Recent developments in MALDI have enabled direct detection of lipids as intact molecular species present within cellular membranes. Abundant lipid-related ions are produced from the direct analysis of thin tissue slices when sequential spectra are acquired across a tissue surface that has been coated with a MALDI matrix. The lipid-derived ions can often be distinguished from other biomolecules because of the significant mass defect that these ions present due to the large number of covalently bound hydrogen atoms in hydrophobic molecules such as lipids. Collisional activation of the molecular ions can be used to determine the lipid family and often structurally define the molecular species. Specific examples in the detection of phospholipids, sphingolipids, and glycerolipids are presented with images of mouse brain and kidney tissue slices. Regional distribution of many different lipid molecular species and Na+ and K+ attachment ions often define anatomical regions within the tissues.
Close to the Edge: Neutralizing the HIV-1 Envelope (2005)

Haynes
 et al.
 discuss recent findings in
 Science
 and
 Nature Medicine
 about antibodies directed to the membrane-proximal region (MPR) of the HIV-1 envelope (ENV) glycoprotein and their possible therapeutic utility. Although these antibodies have the desirable trait of neutralizing the virus in vitro, they occur only rarely in patients, possibly because they also react with self-antigens such as the lipid cardiolipin, and so are eliminated. In addition, the MPR region of HIV-1 may not be accessible to this antibody in patients, limiting its usefulness. Nevertheless, Haynes
 et al.
 indicate that further work on neutralizing antibodies that target the conserved Env protein of HIV-1 is warranted.
LONG-TERM SECOND-LINE TREATMENT: A PROSPECTIVE DRUG SURVIVAL STUDY (1992)

The long-term use of second-line antirheumatic drugs was prospectively studied in a consecutive sample of 245 patients with recently diagnosed rheumatoid arthritis. A survival analysis was done in which treatment termination due to side-effects and to insufficient therapeutic effect were used as index causes. Cumulative drug 'survival' of aurothioglucose with treatment termination due to toxicity was significantly less compared with hydroxychloroquine. With regard to lack of efficacy as index cause, the administration time of hydroxychloroquine was significantly less than that of either aurothioglucose or sulphasalazine. Treatment termination due to lack of efficacy or combined insufficient therapeutic response and toxicity proved to be influenced by the initial disease activity and by the rank order of prescription.
The role of nitric oxide in experimental murine sepsis due to pyrogenic exotoxin A-producing Streptococcus pyogenes (1997)

Nitric oxide (NO) produced by inducible NO synthase (iNOS) mediates hypotension in endotoxemia. In this study, NO induction by a toxin-producing Streptococcus pyogenes isolate, H250, and by recombinant streptococcal pyrogenic exotoxin A (rSPEA) has been examined, both in vitro and in vivo. Streptococcal supernatants, but not rSPEA, induce production of nitrite by murine macrophages when both are coincubated with gamma interferon. Intraperitoneal injection of rSPEA did not cause significant production of NO. However, an elevated level of nitrate in serum was detected in a model of streptococcal fasciitis due to live H250. iNOS was localized to Kupffer cells, hepatocytes, and renal tubular cells by immunostaining. Administration of a NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), reduced peak concentrations of nitrate in serum but did not affect survival. NO is induced by H250, both in vitro and in vivo, mainly via SPEA-independent mechanisms. In this model, iNOS is expressed predominantly in the liver. Furthermore, in this model L-NMMA is not protective.
Overexpression of HOXA10 perturbs human lymphomyelopoiesis in vitro and in vivo (2001)

Several studies point to multiple members of the Hox transcription factor family as playing key roles in normal hematopoietic development, and they link the imbalanced expression of these transcription factors, in particular of the Abd-like A cluster HOX genes HOXA9 and HOXA10, to leukemogenesis. To test directly the hypothesis that HOXA10 is involved in human hematopoietic development, the gene was retrovirally overexpressed in human highly purified CD34(+)/GFP(+) hematopoietic progenitor cells derived from cord blood or fetal liver sources, and the impact of aberrant gene expression was analyzed on differentiation and proliferation in vitro and in vivo. HOXA10 misexpression profoundly impaired myeloid differentiation with a higher yield of blast cells in liquid culture and a greater than 100-fold increased generation of blast colonies after in vitro expansion or after replating of primary colonies first plated in methylcellulose directly after transduction (P < .01). Furthermore, aberrant HOXA10 expression almost completely blocked erythroid differentiation in methylcellulose (P < .02). HOXA10 deregulation also severely perturbed the differentiation of human progenitors in vivo, reducing B-cell development by 70% in repopulated NOD/SCID mice and enhancing myelopoiesis in the transduced compartment. The data provide evidence that the balanced expression of HOXA10 is pivotal for normal human hematopoietic development and that aberrant expression of the gene contributes to impaired differentiation and increased proliferation of human hematopoietic progenitor cells. These results also provide a framework to initiate more detailed analyses of HOX regulatory domains and HOX cofactors in the human system in vitro and in vivo.
Shale Gas Characteristics of Permian Black Shales in South Africa: Results from Recent Drilling in the Ecca Group (Eastern Cape) (2013)

Detailed lithological, sedimentological, petrographic and geochemical analyses of the lower three formations of the Ecca Group in the Greystone area, Eastern Cape, South Africa, close to the tectonic front of the Cape Fold Belt, are described with a particular focus on the black shales of the Whitehill Formation. Fresh core samples from a 300m deep borehole were analysed as follows: petrography, XRD and XRF, open system pyrolysis and thermovaporization, TOC/Rock Eval, SEM microscopy, vitrinite reflectance, stable isotopes and porosity using mercury intrusion. This ongoing investigation gives insight into the gas potential of the Karoo black shales.
Meta-structure transformation model for statistical machine translation (2007)

We propose a novel syntax-based model for statistical machine translation in which meta-structure (MS) and meta-structure sequence (SMS) of a parse tree are defined. In this framework, a parse tree is decomposed into SMS to deal with the structure divergence and the alignment can be reconstructed at different levels of recombination of MS (RM). RM pairs extracted can perform the mapping between the sub-structures across languages. As a result, we have got not only the translation for the target language, but an SMS of its parse tree at the same time. Experiments with BLEU metric show that the model significantly outperforms Pharaoh, a state-art-the-art phrase-based system.
Quantitative studies on the bactericidal actions of serum and complement. II. Some implications for the mechanism of the bactericidal reaction. (1956)

Summary The bactericidal reaction, as studied with a new photometric growth assay, has been shown to parallel the hemolytic reaction in a number of respects: a stimulation by, if not an absolute requirement for, Mg ion and antibody-complement relations which can be expressed by identical equations. In a typical experiment 700–860 molecules of antibody and 1.5 × 10 7 molecules of complement were necessary to kill one organism, Salmonella typhosa , at the 50% end point. This amount of antibody is calculated to cover 0.03–0.7% of the bacterial cell surface. Heating at 56°C for a few minutes has been shown to decrease the bactericidal activity, particularly of weak sera, by partial destruction of antibody. Rabbit serum has an activating effect on guinea pig complement, human serum a depressing effect in the bactericidal although not in the hemolytic reaction. The relative titer of two sera is shown to vary with heating, and the species of complement used. Additional observations are presented on the Neisser-Wechsberg inhibition, and the mechanism of the bactericidal effect.
Frequent latent Epstein-Barr virus infection of neoplastic T cells and bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas (1993)

We investigated 81 cases of peripheral pleomorphic T-cell lymphoma (PMTCL) occurring in human immunodeficiency virus-negative Europeans for the presence of Epstein-Barr virus (EBV)-DNA through polymerase chain reaction (PCR) for the presence of EBV-encoded small nuclear RNAs (EBER) and immediate early mRNAs (Bam H-fragment, lower strand frame [BHLF]) by in situ hybridization (ISH) and for EBV-encoded latent membrane protein (LMP) and nuclear antigen 2 (EBNA2) by immunohistology (IH). EBER-ISH, which could be applied on all cases, showed an overall incidence of EBV-infected cells in 38 of 81 cases (47%) of PMTCL. These data could be confirmed by PCR, which produced congruent results in the cases with amplifiable DNA. By EBER-ISH, the virus was located in the tumor cells in 30 of the 38 EBV-positive cases, with the proportion of the infected cells ranging from 1% to 100%. In 18 of these cases and in the 8 cases without EBV-infected tumor cells, the virus was, respectively, either additionally or exclusively detectable in occasional nonmalignant lymphoid bystander cells. An LMP expression was observed in several of the EBER-expressing tumor cells in 18 cases, whereas EBNA2 was detectable only in one case, which also displayed signs of viral replication. Some nonmalignant EBV-infected B immunoblasts also expressed LMP in several cases. Primary cutaneous and enteropathy-associated PMTCL displayed less frequent EBV infection when compared with other extranodal or nodal manifestations.
Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. (1986)

Two human B-cell differentiation antigens, Bp35 and Bp50, apparently play distinct roles as signal receptors in B-cell activation. Monoclonal antibodies (mAbs) to either Bp35 or Bp50 deliver positive signals to B cells that stimulate their transition through the cell cycle. mAb to Bp35, like anti-immunoglobulin antibodies, functions principally to activate resting B cells to become competent to enter the G1 phase of the cell cycle. In contrast, mAb to Bp50, a 50-kDa polypeptide expressed on all B cells, functions to stimulate activated B cells to traverse the cell cycle. mAb to Bp35, like anti-immunoglobulin antibodies, activates tonsillar B cells and induces low levels of B-cell proliferation. In contrast, anti-Bp50 mAb alone neither activates B cells nor induces B cells to proliferate but, together with anti-Bp35 or anti-immunoglobulin, augments B-cell proliferation. In this respect the action of anti-Bp50 antibody resembles the activity of B-cell growth factor(s) (BCGF). As little as 0.05 microgram of anti-Bp50 per ml is needed to augment proliferation and, like BCGF, anti-Bp50 is effective even when added 12-24 hr after B cells are activated with anti-immunoglobulin or anti-Bp35. Without additional exogenous signals, anti-Bp35 and anti-Bp50 together induce strong proliferation of purified resting B cells. These results suggest that the Bp35 and Bp50 surface molecules function in the regulatory control of B-cell activation and progression through the cell cycle.
Differential expression of chemokines in synovial cells exposed to different Borrelia burgdorferi isolates. (2005)

This study suggests that the orchestra of chemokines plays an important role in the immunopathogenesis of early Lyme arthritis.
Gene Therapy of Canavan Disease: AAV-2 Vector for Neurosurgical Delivery of Aspartoacylase Gene ( ASPA ) to the Human Brain (2002)

This clinical protocol describes virus-based gene transfer for Canavan disease, a childhood leukodystrophy. Canavan disease, also known as Van Bogaert-Bertrand disease, is a monogeneic, autosomal recessive disease in which the gene coding for the enzyme aspartoacylase (ASPA) is defective. The lack of functional enzyme leads to an increase in the central nervous system of the substrate molecule, N-acetyl-aspartate (NAA), which impairs normal myelination and results in spongiform degeneration of the brain. No effective treatment currently exists; however, virus-based gene transfer has the potential to arrest or reverse the course of this otherwise fatal condition. This procedure involves neurosurgical administration of approximately 900 billion genomic particles (approximately 10 billion infectious particles) of recombinant adeno-associated virus (AAV) containing the aspartoacylase gene (ASPA) directly to affected regions of the brain in each of 21 patients with Canavan disease. Pre- and post-delivery assessments include a battery of noninvasive biochemical, radiological, and neurological tests. This gene transfer study represents the first clinical use of AAV in the human brain and the first instance of viral gene transfer for a neurodegenerative disease.
Synthesis and biodistribution of neutral lipid-soluble Tc-99m complexes that cross the blood-brain barrier. (1984)

Three Tc-99m-labeled neutral 1,2-dithia-5,8-diazacyclodecane (BAT) chelates that are capable of crossing the blood-brain barrier (BBB) were prepared and evaluated. Biodistribution (i.v.) in rats showed a significant brain uptake (1-3%/whole brain) at 2 min. At 15 min the uptake dropped to about a tenth of the original level, indicating free passage in both directions across the BBB. Gamma camera images of a monkey confirmed the high initial brain uptake. This group of Tc-99m BAT compounds clearly exhibited in vivo stability and the ability to cross the BBB after an i.v. injection. Derivatives containing tertiary amine groups should have prolonged brain retention and might be suitable for SPECT studies of brain perfusion.
Nuclear expression of CDK4 correlates with disease progression and poor prognosis in human nasopharyngeal carcinoma (2013)

Our findings suggest that nuclear expression of CDK4 is a potential marker for the progression and poor prognosis of NPC.