Miracle-dz/UniFAR-FTUs huggingface dataset:
On the Nature of Neoplasia in Man: W. Smithers: E. & S. Livingstone Ltd., Edinburgh and London: Pp. 176. Price 25s.

The achievements of antibiotics in the management of bacterial diseases have greatly stimulated research into the chemotherapy of malignant disease. Hormones, antimetabolites and the alkylating agents have so far proved to be the most useful of the many classes of compounds which have been investigated. The authors of this book, working at Moscow University, have examined the anti-tumour effects of various bacterial and protozoa! preparations. Of the latter group, extracts obtained from Trypanosoma cruzi were found to the most active. The results which they have obtained from the use of these extracts in experimentally induced tumours in animals and in clinical trials in human cancers form the basis of the book, which was first published in 1957 in Russia. This edition, translated into English, possesses an additional section summarizing the results of several independent clinical trials carried out in France. The writing is verbose and repetitive. The international literature is well covered by the references, but the index is sparse and inadequate. The subject matter is presented poorly. Preparation of the Trypanosomal extracts is not described in detail. The extracts were unstable and varied in potency. It appears that they were more effective in the animal trials than in human diseases, and that results were improved by excision of the tumour after an initial response had been obtained. Nevertheless, the effects which are claimed cannot be dismissed lightly, and it would seem that fractionation of T. cruzi extracts by modem methods and investigation of concentrates so obtained might be worthy of further trial by organizations such as the National Cancer Institutes in the U.S.A. or by the Medical Research Council in Britain. The book ought to be available for reference in specialist libraries, but is unlikely to be of value to general readers. n'A. KOK
Al2O3 films (ALD) elemental composition study by ToF-SIMS at different thermal processing

Integration of materials with a high dielectric constant into storage or gate capacitor applications requires a detailed understanding of the elemental and the phase composition behavior during calcination processes. In this work the elemental and the phase composition of Al2O3 films on silicon substrates obtained technology atomic layer deposition were studied. The investigations were performed before and after samples heat at different temperatures by TOF secondary ion mass spectrometry. Comparative analysis of the elemental composition and its distribution changes at Al2O3/Si interface was carried out.
Incentivos para la actividad distrital de los diputados: el caso del sistema electoral mixto en Bolivia*

In this paper we analyze the incentives created by the electoral system to encourage dis - trict activity of legislators. We analyze the case of Bolivia, a country that, since 1994, has employed a mixed electoral system where legislators are elected in single-member and mul - ti-member districts simultaneously . We work with the hypothesis that the elected legislators in these two types of constituencies need to show efficiency in their work as representatives, either for their own benefit or for the benefit of their party . In this paper we argue that the significant differences between Bolivian legislators elected in single-member constituencies and those elected in multi-member constituencies are related to the strategies used to reach out to voters, to social sectors and to parties .
Infertility improved by etanercept in ankylosing spondylitis

The effect of TNF-α and TNF-α antagonists on semen quality in men is controversial. TNF-α levels are usually low in seminal plasma, but they tend to increase in inflammatory and infectious diseases. Etanercept is a highly-specific antagonist of TNF-α. In this report, we describe the development of pregnancy in a couple with a previously infertile husband, who received etanercept for ankylosing spondylitis.
Analysis of user behavior with multimodal virtual customer service agents

We investigate the occurrence of user restatement when there is no apparent error in Intelligent Virtual Assistant (IVA) understanding in a multimodal customer service environment. We define several classes of response medium combinations and use various statistical measures to determine how the combination of medium and linguistic complexity impacts the user's apparent willingness to accept their query result. Through analysis on 3; 000 sessions with a live customer service IVA deployed on an airline company website and mobile application, we discover that as more media are involved in a response, user restatements increase. We also determine which linguistic complexity measures should be minimized for every response class in order to improve user comprehension.
Pathophysiology and Clinical Implications of Cardiac Memory

Altering the pattern of activation of the ventricle causes remodeling of the mechanical and electrical properties of the myocardium. The electrical remodeling is evident on the surface electrocardiogram as significant change in T‐wave polarity following altered activation; this phenomenon is ascribed to as “T‐wave memory” or “cardiac memory. ” The electrophysiological remodeling following altered activation is characterized by distinct changes in regions proximal (early‐activated) versus distal (late‐activated) to the site of altered activation. The early‐activated region exhibits marked attenuation of epicardial phase 1 notch due to reduced expression of the transient outward potassium current (Ito). This is attributed to electrotonic changes during altered activation, and angiotensin‐mediated regulation of Kv4.3 (the pore‐forming α subunit responsible for Ito). The late‐activated region exhibits the most significant action potential prolongation due to markedly increased mechanical strain through a mechano‐electrical feedback mechanism. Consequently, regionally heterogeneous action potential remodeling occurs following altered activation. This enhances regional repolarization gradients that underlie the electrophysiological basis for T‐wave memory. Further, recent clinical studies highlight detrimental consequences of altered activation including worsening mechanical function and increased susceptibility to arrhythmias. Future studies to identify molecular mechanisms that link electrotonic and mechanical strain‐induced changes to cellular electrophysiology will provide important insights into the role of altered activation in regulating cardiac repolarization and arrhythmogenesis. (PACE 2010; 33:346–352)
DEPOSITION OF PYRETHRINS AND PIPERONYL BUTOXIDE FOLLOWING AERIAL ULTRA-LOW VOLUME APPLICATIONS IN THE COACHELLA VALLEY, CALIFORNIA

ABSTRACT Data on adulticide deposition were collected during studies optimizing aerial ultra-low volume applications and droplet size in the desert environment of the Coachella Valley, Riverside County, California. Pyrenone 25-5® and BVA Spray 13® oil were applied by a single-engine, fixed wing aircraft equipped with 2 Micronair® AU5000 atomizers. Data recorded by a portable weather station documented that weather conditions were suitable for application. Adulticide residue was collected using 24-cm-diameter filter papers positioned along 2–3 transects, with 3 positive controls held outside of the treated zone. The trace amounts of 2 major insecticidal components (pyrethrin I and II) and the synergist piperonyl butoxide (PBO) were detected from samples near the center of the spray zone by high-performance liquid chromatography (HPLC); pyrethrin deposition was highest at the center, 156 µg/m2, and it was not detectable 60 m beyond the center of the transect, whereas PBO deposition was 5,000 µg/m2 at the center but was not detectable beyond 150 m. Droplet diameters on spinning Teflon® slides were larger than expected for the rated output of the atomizers. For these single swath trials, the lack of swath overlap due to drift resulted in low mortality in sentinel mosquitoes. Detection of residues was limited to the centroid of droplet densities on spinning glass slides and with mortality among sentinel mosquitoes, indicating HPLC may be useful in detecting postspray residues.
Phage-Displayed T-Cell Epitope Grafted into Immunoglobulin Heavy-Chain Complementarity-Determining Regions: an Effective Vaccine Design Tested in Murine Cysticercosis

ABSTRACT A new type of immunogenic molecule was engineered by replacing all three complementarity-determining-region (CDR) loops of the human immunoglobulin (Ig) heavy-chain variable (VH) domain with the Taenia crassiceps epitope PT1 (PPPVDYLYQT) and by displaying this construct on the surfaces of M13 bacteriophage. When BALB/c mice were immunized with such phage particles (PIgphage), a strong protection against challenge infection in very susceptible female hosts was obtained. When specifically stimulated, the in vivo-primed CD4+ and CD8+ T cells isolated from mice immunized with PT1, both as a free peptide and as the PIgphage construct, proliferated in vitro, indicating efficient epitope presentation by both major histocompatibility complex class II and class I molecules in the specifically antigen-pulsed macrophages used as antigen-presenting cells. These data demonstrate the immunogenic potential of recombinant phage particles displaying CDR epitope-grafted Ig VH domains and establish an alternative approach to the design of an effective subunit vaccine for prevention of cysticercosis. The key advantage of this type of immunogen is that no adjuvant is required for its application. The proposed strategy for immunogen construction is potentially suitable for use in any host-pathogen interaction.
Changes in the host lymphocyte subsets during chemical carcinogenesis.

Changes in small lymphocyte subsets in the lymphoid organs of young C3H mice were studied following i.m. injection of a carcinogenic dose of 3-methylcholanthrene in trioctanoin oil. Using monoclonal anti-Lyt antibodies and a sandwich radiolabeling method with 125I-labeled rabbit anti-mouse Immunoglobulin, the lymphocyte subpopulations in the thymus, spleen, and draining lymph node were examined by radioautography. During the fifth week following the administration of the carcinogen and prior to the appearance of histologically evident tumor cells, a sharp decrease in the level of Ly-1,2+ small lymphocyte population in the thymus was noted which coincided with a considerable increase (10-fold) in the Ly-2+ and a small increase (1.7-fold) in the Ly-1+ population. During the same period, a similar increase in the Ly-2+ population was also observed in the draining but not in the contralateral lymph node. The high levels of Ly-2+ cells lasted for more than 4 weeks in the thymus while, in the draining node, they lasted for 2 weeks and dropped to normal levels (0 to 2%) simultaneously with the appearance of tumor cells identified in histological preparations. Smaller increases (3-fold) in the Ly-2+ subset were also noted in the spleen and contralateral node, but they were seen later (7 to 8 weeks) and were shorter in duration. These systemic increases coincided with the appearance of macroscopic tumor nodules. The relative incidence of immunoglobulin+ cells did not change significantly in any of the organs tested during the entire tumor induction phase, while the level of null cells underwent a slight increase (approximately 2-fold) in all organs tested immediately prior to and following the appearance of macroscopic tumors. None of these changes was observed in trioctanoin oil-injected control animals. The mixed lymphocyte reaction response of the draining node cells, but not of the spleen, was suppressed during the period of increased level of Ly-2+ cells. Furthermore, during this period, s.c. transplantation of a syngeneic mammary tumor in the same leg resulted in enhanced local growth as well as metastatic spread of the tumor to the lungs in 3-methylcholanthrene-treated mice. These findings suggest that a localized immunosuppression associated with the rise in the Ly-2+ cells may be of functional significance during carcinogen-induced tumor development.
Opening of connexin 43 hemichannels is increased by lowering intracellular redox potential

Nonjunctional membrane in many cells contains connexin gap junction hemichannels (or connexons) that can open to allow permeation of small molecules. Opening of Cx43 hemichannels is infrequent in normal extracellular Ca2+ and enhanced by low Ca2+, positive membrane potentials, and dephosphorylation of critical residues. Here we report that lowering intracellular redox potential increases Cx43 hemichannel open probability under otherwise normal conditions. We studied dye uptake and single-channel activity in HeLa cells transfected with wild-type Cx43, Cx43 with enhanced GFP attached to its C terminus (Cx43-EGFP), and Cx43 with enhanced GFP attached to its N terminus (EGFP-Cx43). Dithiothreitol [(DTT) 10 mM], a membrane permeant-reducing agent, increased the rate of dye uptake by cells expressing Cx43 and Cx43-EGFP, but not by parental cells or cells expressing EGFP-Cx43. Induced dye uptake was blocked by La3+, by a peptide gap junction and hemichannel blocker (gap 26), and by flufenamic acid. DTT increased Cx43-EGFP hemichannel opening at positive voltages. Bath application of reduced glutathione, a membrane impermeant-reducing agent, did not increase dye uptake, but glutathione in the recording pipette increased hemichannel opening at positive voltages, suggesting that it acted intracellularly. DTT caused little change in levels of surface Cx43 or Cx43-EGFP, or in intracellular pH. These findings suggest that lowering intracellular redox potential increases the opening of Cx43 and Cx43-EGFP hemichannels, possibly by action on cytoplasmic cysteine residues in the connexin C terminus.
Development and Characterization of a Human In Vitro Resorption Assay: Demonstration of Utility Using Novel Antiresorptive Agents

A human in vitro resorption assay has been developed using osteoclastoma‐derived osteoclasts and used to evaluate novel antiresorptive agents including antagonists of the αvβ3 integrin, and inhibitors of cathepsin K and the osteoclast ATPase. The potency of novel compounds in the in vitro resorption assay correlates with functional assays for each class of inhibitor: the human αvβ3‐mediated cell adhesion assay for the vitronectin receptor antagonists (r2 = 0.82), the chick osteoclast vacuolar ATPase enzyme assay for the H+‐ATPase inhibitors (r2 = 0.77) and the recombinant human cathepsin K enzyme assay for the cathepsin K inhibitors (r2 = 0.80). Cell suspensions, rich in osteoclasts, are prepared by collagenase digestion of the tumor tissue. These cells can be stored long‐term in liquid nitrogen and upon thawing maintain their bone‐resorbing phenotype. The cryopreserved cells can be cultured on bovine cortical bone for 24–48 h and resorption can be measured by either confocal microscopy or biochemical assays. The resorptive activity of osteoclasts derived from a number of tumors can be inhibited reproducibly using a number of mechanistically unique antiresorptive compounds. In addition, the measurement of resorption pits by laser confocal microscopy correlates with the release of type I collagen C‐telopeptides or N‐telopeptides, as measured by enzyme‐linked immunosorbent assay. Resorption can be measured reproducibly using a 48‐h incubation of osteoclasts on bone slices, or a 24‐h incubation with bone particles. This in vitro human osteoclast resorption assay provides a robust system for the evaluation of inhibitors of osteoclastic function that may be developed for the treatment of metabolic bone diseases such as osteoporosis.
Unrealistic optimism: a behavioural sciences classroom demonstration project

Summary: Unrealistic optimism may contribute to risky health practices and to a delay in seeking treatment for medical conditions, as most individuals perceive themselves to be at little risk for various disorders. It is thus an important concept to present to medical students as part of their behavioural sciences training. Social psychological concepts such as unrealistic optimism may appear, on initial presentation to students, to be a misjudgement based on faulty understanding of risk estimates by the general population. This project aimed to teach the principle of unrealistic optimism by having students document their own beliefs about health risks. Students rated their own risk, relative to other classmates, of experiencing a range of 17 health problems. Questionnaires were completed by two classes of medical students (n= 257). Class results showed varying levels of unrealistic optimism for all 17 conditions. Males and females differed significantly on three of the 17 conditions. Student data were obtained rapidly in a large didactic setting and served to illustrate the concept of unrealistic optimism which was subsequently taught in class. Such exercises may be a useful teaching aid to students providing them with feedback on their own cognitive processes and illustrating that they display cognitive distortions similar to those of patients.
Cloning and Biochemical Characterization of TAF-172, a Human Homolog of Yeast Mot1

ABSTRACT The TATA binding protein (TBP) is a central component of the eukaryotic transcriptional machinery and is the target of positive and negative transcriptional regulators. Here we describe the cloning and biochemical characterization of an abundant human TBP-associated factor (TAF-172) which is homologous to the yeast Mot1 protein and a member of the larger Snf2/Swi2 family of DNA-targeted ATPases. Like Mot1, TAF-172 binds to the conserved core of TBP and uses the energy of ATP hydrolysis to dissociate TBP from DNA (ADI activity). Interestingly, ATP also causes TAF-172 to dissociate from TBP, which has not been previously observed with Mot1. Unlike Mot1, TAF-172 requires both TBP and DNA for maximal (∼100-fold) ATPase activation. TAF-172 inhibits TBP-driven RNA polymerase II and III transcription but does not appear to affect transcription driven by TBP-TAF complexes. As it does with Mot1, TFIIA reverses TAF-172-mediated repression of TBP. Together, these findings suggest that human TAF-172 is the functional homolog of yeast Mot1 and uses the energy of ATP hydrolysis to remove TBP (but apparently not TBP-TAF complexes) from DNA.
A common mechanism for posttranslational activation of plasma membrane receptors?

The process for posttranslational acquisition of ligand binding function is remarkably similar for three receptors with dissimilar structures, namely, the insulin, epidermal growth factor, and acetylcholine receptors. These receptors lack the ability to bind ligand immediately after translation, but slowly (t1/2 = 30‐45 min) acquire this capacity while in the endoplasmic reticulum. This activation step occurs with similar kinetics for all three receptors and, in each case, requires N‐linked glycosylation. Several lines of evidence suggest a common mechanism for the acquisition of ligand binding function that involves the rearrangement of metastable disulfide bonds formed during or immediately after translation. This process precedes subunit assembly of both insulin and acetylcholine receptors, which also occurs in the endoplasmic reticulum. The posttranslational processing steps leading to the acquisition of ligand binding function may be an example of a more general process affecting cell surface proteins. — Olson, T. S. ; Lane, M. D. A common mechanism for posttranslational activation of plasma membrane receptors? FASEB J. 3: 1618‐1624; 1989.
Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein

The adenovirus fiber protein is responsible for attachment of the virion to unidentified cell surface receptors. There are at least two distinct adenovirus fiber receptors which interact with the group B (Ad3) and group C (Ad5) adenoviruses. We have previously shown by using expressed adenovirus fiber proteins that it is possible to change the specificity of the fiber protein by exchanging the head domain with another serotype which recognizes a different receptor (S. C. Stevenson et al., J. Virol. 69:2850-2857, 1995). A chimeric fiber cDNA containing the Ad3 fiber head domain fused to the Ad5 fiber tail and shaft was incorporated into the genome of an adenovirus vector with E1 and E3 deleted encoding beta-galactosidase to generate Av9LacZ4, an adenovirus particle which contains a chimeric fiber protein. Western blot analysis of the chimeric fiber vector confirmed expression of the chimeric fiber protein and its association with the adenovirus capsid. Transduction experiments with fiber protein competitors demonstrated the altered receptor tropism of the chimeric fiber vector compared to that of the parental Av1LacZ4 vector. Transduction of a panel of human cell lines with the chimeric and parental vectors provided evidence for a different cellular distribution of the Ad5 and Ad3 receptors. Three cell lines (THP-1, MRC-5, and FaDu) were more efficiently transduced by the vector containing the Ad3 fiber head than by the Ad5 fiber vector. In contrast, human coronary artery endothelial cells were transduced more readily with the vector containing the Ad5 fiber than with the chimeric fiber vector. HeLa and human umbilical vein endothelial cells were transduced at equivalent levels compared with human diploid fibroblasts, which were refractory to transduction with both vectors. These results provide evidence for the differential expression of the Ad5 and Ad3 receptors on human cell lines derived from clinically relevant target tissues. Furthermore, we show that exchange of the fiber head domain is a viable approach to the production of adenovirus vectors with cell-type-selective transduction properties. It may be possible to extend this approach to the use of ligands for a range of different cellular receptors in order to target gene transfer to specific cell types at the level of transduction.
Cardiovascular risk factor associations in adults with psychosis and adults in a national comparator sample

Objective: Antipsychotic drug treatment alters status on key risk factors for cardiovascular disease. The aim of this study was to test whether cardiovascular risk factor associations differ in adults with psychosis and adults from the general community. Method: Data were analysed for those aged 25–64 years from a nationally representative psychosis sample (n = 1,457) and a national comparator sample (n = 8,866). The Pearson correlation coefficient was used to estimate the association among tobacco use, body mass index, waist circumference, diastolic and systolic blood pressure and fasting total-, LDL- and HDL-cholesterol, triglycerides and plasma glucose. The robust Levene test was used to test for sample differences in variance. Results: Correlations among cardiovascular risk indicators and between cardiovascular risk indicators and age were often significantly weaker in those with psychosis than in those from the national comparator sample. This was not due to a reduction in variance within the psychosis sample. Conclusions: Risk prediction that synthesizes multivariate risk indicator data needs to be connected to verified cardiovascular morbidity and mortality in those with psychosis to determine if standard risk calculators adequately discriminate those at high, medium and low future risk of cardiovascular morbidity and mortality. Until then the clinical implications of low or absent correlations among cardiovascular risk indicators and their low or absent association with increasing age is unclear but may indicate that risk equations commonly used in the general population may not be applicable for those with treated psychosis.