Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for more than one type of non‐NMDA receptor in outside‐out patches from cerebellar granule cells of the rat.

1. Application of non‐NMDA (non‐N‐methyl‐D‐aspartate) receptor agonists onto outside‐out patches of cerebellar granule cells gave two characteristic types of response (in different patches) which we have referred to as ‘high conductance’ and ‘low conductance’ responses. At a qualitative level these patches could be readily distinguished by the size of the noise increase accompanying their membrane currents. 2. In high conductance patches both AMPA (alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid) and kainate gave discrete single‐channel conductances (10‐30 pS), while in low conductance patches, AMPA produced small discrete events (6‐10 pS), and kainate opened channels with conductances too small to be directly resolved. All patches examined contained NMDA receptor channels with characteristic 50 and 40 pS conductance levels. 3. Despite the marked differences in single‐channel conductances, kainate dose‐response curves constructed for high and low conductance patches had similar EC50 values of approximately 150 microM. 4. Spectral analysis of low conductance kainate responses gave an estimated channel conductance of approximately 1.5 pS. In these same low conductance patches AMPA produced discrete openings with two conductance levels; their mean conductances (and relative proportions) were 6 (87%) and 10 pS (13%). 5. In high conductance patches, glutamate (10‐30 microM), AMPA (3‐10 microM), and kainate (10‐30 microM), each activated non‐NMDA channels with three multiple conductance levels. The amplitudes of these conductance levels (approximately 10, 20 and 30 pS) were similar for each of the agonists, and their relative proportions (i.e. areas in the amplitude histograms) were constant for all three agonists. In addition, the relative proportion of levels was constant between patches, and all three levels were invariably present. These observations are all consistent with the idea that the three multiple conductances originate from a single receptor channel, activated by AMPA, kainate and glutamate. 6. Non‐NMDA single‐channel current‐voltage (I‐V) plots showed outward rectification in high conductance patches. For all three multiple conductance levels the ratio of outward to inward single‐channel slope conductance was 1.8 +/‐ 0.1 and this rectification remained present in symmetrical Na+ solutions. 7. In high conductance patches, the events produced by a rapid application of 20‐50 microM glutamate were compared with those activated during steady‐state application. (ABSTRACT TRUNCATED AT 400 WORDS)
Studies on the Cherenkov Effect for Improved Time Resolution of TOF-PET

With the newly gained interest in the time-of-flight method for positron emission tomography (TOF-PET), many options for pushing the time resolution to its borders have been investigated. As one of these options, the exploitation of the Cherenkov effect has been proposed, since it allows to bypass the scintillation process and therefore provides almost instantaneous response to incident 511 keV annihilation photons. Our simulation studies on the yield of Cherenkov photons, their arrival rate at the photon detector, and their angular distribution reveal a significant influence by Cherenkov photons on the rise time of inorganic scintillators - a key-parameter for TOF in PET. A measurement shows the feasibility to detect Cherenkov photons in this low energy range.
Determination of vertical characteristics with different cephalometric measurements

Objective: To analyze a possible correlation between different measures in the definition of vertical facial types. Materials and Methods: This is an analytical observational study about 95 lateral teleradiographs of Caucasian individuals with normal occlusion, of which 54 were male (56.84%) and 41 female (43.16%), aged between 15 years and 2 months old and 21 years and 4 months old. Facial types were divided into dolichofacial, mesofacial, and brachyfacial, according to the standards established by different authors. A relationship between these measurements was verified using total agreement analysis and the Kappa method, with the interpretation suggested by Landis and Koch. Results: Kappa was considered fair for Jarabak X VERT (0.22 and 60%) and slight for Jarabak X SN.GoGn (0.06 and 36.8%). Conclusions: Cephalometric studies often present different interpretations on the description of vertical facial types. In this study, the lowest agreement was between Jarabak and SN.GoGn. Such difference in interpretation may lead to distinct therapeutic approaches and thus different results.
Chances and limitations of non‐invasive tests in the assessment of liver fibrosis in liver transplant patients

Kamphues C, Lotz K, Röcken C, Berg T, Eurich D, Pratschke J, Neuhaus P, Neumann UP. Chances and limitations of non‐invasive tests in the assessment of liver fibrosis in liver transplant patients. Clin Transplant 2009 DOI:10.1111/j.1399‐0012.2009. 01152.x © 2009 John Wiley & Sons A/S.
Knowledge-based signal processing in the decomposition of myoelectric signals

The mixture of quantitative and qualitative information utilized in decomposition, which suggests that a purely numerical approach to the task would be inefficient, is discussed. The incorporation of symbolic processing methods into the decomposition system to complement the numerical aspects of the task is discussed. The overall philosophy used in the decomposition system is examined, focusing on the principles of detection used. The organization of the software used by the system is described. <<ETX>>
Aspirin induces apoptosis in vitro and inhibits tumor growth of human hepatocellular carcinoma cells in a nude mouse xenograft model

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to induce apoptosis in a variety of cancer cells, including colon, prostate, breast and leukemia. Among them, aspirin, a classical NSAID, shows promise in cancer therapy in certain types of cancers. We hypothesized that aspirin might affect the growth of liver cancer cells since liver is the principal site for aspirin metabolism. Therefore, we investigated the effects of aspirin on the HepG2 human hepatocellular carcinoma cell line in vitro and the HepG2 cell xenograft model in BALB/c nude mice. We found that treatment with aspirin inhibited cell growth and induced apoptosis involving both extrinsic and intrinsic pathways as measured by DNA ladder formation, alteration in the Bax/Bcl-2 ratio, activation of the caspase activities and related protein expressions. In vivo antitumor activity assay also showed that aspirin resulted in significant tumor growth inhibition compared to the control. Oral administration of aspirin (100 mg/kg/day) caused a significant reduction in the growth of HepG2 tumors in nude mice. These findings suggest that aspirin may be used as a promising anticancer agent against liver cancer.
Automatic, template-based run-time specialization: implementation and experimental study

Specializing programs with respect to run time values has been shown to drastically improve code performance on realistic programs ranging from operating systems to graphics. Recently, various approaches to specializing code at run time have been proposed. However, these approaches still suffer from shortcomings that limit their applicability: they are manual, too expensive, or require programs to be written in a dedicated language. We solve these problems by introducing new techniques to implement run time specialization. The key to our approach is the use of code templates. Templates are automatically generated from ordinary programs and are optimized before run time, allowing high quality code to be quickly generated at run time. Experimental results obtained on scientific and graphics code indicate that our approach is highly effective. Little run time overhead is introduced, since code generation primarily consists of copying instructions. Run time specialized programs run up to 10 times faster, and are nearly as fast as fully optimized programs (80% on average). The combination of low run time overhead and high code quality enables specialization to be amortized in as few as 3 runs. Although this approach is highly effective, its implementation is relatively simple since it exploits existing partial evaluation and compiler technologies.
Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10) Receptor-1 Mimetics

Tackling protein interfaces with small molecules capable of modulating protein-protein interactions remains a challenge in structure-based ligand design. Particularly arduous are cases in which the epitopes involved in molecular recognition have a non-structured and discontinuous nature. Here, the basic strategy of translating continuous binding epitopes into mimetic scaffolds cannot be applied, and other innovative approaches are therefore required. We present a structure-based rational approach involving the use of a regular expression syntax inspired in the well established PROSITE to define minimal descriptors of geometric and functional constraints signifying relevant functionalities for recognition in protein interfaces of non-continuous and unstructured nature. These descriptors feed a search engine that explores the currently available three-dimensional chemical space of the Protein Data Bank (PDB) in order to identify in a straightforward manner regular architectures containing the desired functionalities, which could be used as templates to guide the rational design of small natural-like scaffolds mimicking the targeted recognition site. The application of this rescaffolding strategy to the discovery of natural scaffolds incorporating a selection of functionalities of interleukin-10 receptor-1 (IL-10R1), which are relevant for its interaction with interleukin-10 (IL-10) has resulted in the de novo design of a new class of potent IL-10 peptidomimetic ligands.
[The proportional mortality ratios of specific-cause mortality by occupation and education among men aged 20-64 in Korea (1993-2004)].

OBJECTIVES This study investigated the relationship of occupational class and educational background with proportional mortality ratios in Korea. METHODS Mortality was investigated using the entire registered death data from 1993 to 2004, obtained from the Korean National Statistics Office. Proportional mortality ratios (PMRs) for specific diseases were calculated according to the occupational class and educational background of men aged 20-64. RESULTS Manual workers were found to have higher PMRs for liver disease and traffic accidents, as did the lower educated group. Especially, this study showed trends of an increasing of the wide gap between lower and higher socioeconomic stati for liver disease, traffic accidents, diabetes mellitus and cerebral vascular disease. The mortality for cerebrovascular disease, diabetes mellitus, heart disease, traffic accident and liver disease showed increasing trends according to the calendar year for the lower than the higher social class. CONCLUSIONS The specific conditions that had higher PMRs in the Korean lower social class were liver disease and traffic accidents. Especially, there was an increasing trend for a widening of the gap between manual and non-manual groups in relation to mortality from liver disease, diabetes mellitus and traffic accidents.
A Controlled Phase Ii Trial Assessing Three Doses of Enfuvirtide (T-20) in Combination with Abacavir, Amprenavir, Ritonavir and Efavirenz in Non-Nucleoside Reverse Transcriptase Inhibitor-Naive HIV-Infected Adults

Enfuvirtide is a novel antiretroviral that blocks HIV-1 cell fusion and viral entry. This Phase II, controlled, open-label, randomized, multicentre dose-ranging trial explored the safety, antiviral activity and pharmacoki-netics of enfuvirtide, administered by subcutaneous (SC) injection, in 71 HIV-1-infected, protease inhibitor-experienced, non-nucleoside reverse transcriptase inhibitor (NNRTI)-naive adults for 48 weeks. Study participants were randomized to receive enfuvirtide at a deliverable dose of 45, 67.5 or 90 mg twice daily; the 45 mg twice daily dose required 2 injections/day, while the higher doses required 4 injections/day. A background oral antiretroviral (ARV) regimen of abacavir (300 mg twice daily), amprenavir (1200 mg twice daily), ritonavir (200 mg twice daily) and efavirenz (600 mg once daily) was provided with enfuvirtide. A control group received the background ARV regimen alone. All potential participants underwent an HIV genotype at screen to ensure a homogenous population and to exclude patients with evidence of genotypic resistance to NNRTIs. Overall, the tolerability of the combination of abacavir, amprenavir, ritonavir, efavirenz and enfuvirtide was generally comparable to control through 48 weeks. No enfuvirtide dose-dependent adverse events (AEs) were observed across treatment groups. Injection site reactions (ISRs) occurred at least once in 68.5% of the enfuvirtide-treated population, and most ISRs were mild to moderate in severity, with no apparent dose relationship. Excluding ISRs, the most common treatment-emergent AEs were nausea, diarrhoea, dizziness and fatigue; with no clinically significant differences in the incidence of AEs observed between the control and enfuvirtide groups. Each treatment group benefited from ARV therapy, with a trend of increasing antiviral and immunological activity associated with increasing enfuvirtide dose. At 48 weeks, the median HIV-1 RNA change from baseline for the ITT population was –2.24 log10 copies/ml for the combined enfuvirtide groups compared with –1.87 log10 copies/ml for the control group. In addition, 54.9% of patients in the enfuvirtide group achieved HIV-1 RNA ≤400 copies/ml versus 36.8% of patients in the control group. These results indicate that enfuvirtide has a favourable safety profile and is a promising new antiviral agent for HIV-infected patients who have been on previously failing ARV regimens.
Managing emissions of active pharmaceutical ingredients from manufacturing facilities: An environmental quality standard approach

Active pharmaceutical ingredient (API) residues have been found to be widespread in the aquatic environment, albeit in most cases at trace levels, with the route to the environment predominantly being via therapeutic use and subsequent excretion to sewer. Although manufacturing discharges may be a low overall contributor to environmental concentrations, they need to be managed effectively so that they do not adversely affect the local receiving environment. In order to achieve this, a risk‐based approach is proposed that identifies the long‐term and short‐term concentrations, referred to as environmental reference concentrations (ERCs) and maximum tolerable concentrations (MTCs), respectively, of an API which should not be exceeded in the aquatic environment receiving effluent from pharmaceutical manufacturing sites. The ERC approach is based on established environmental quality standard concepts currently used in much national and international legislation. Building on these concepts, the approach takes into account indirect exposure of potential consumers such as fish‐eating mammals and humans, as well as primary producers (e.g., algae) and primary and secondary consumers (e.g., invertebrates and fish). Although chronic toxicity data are preferred for ERC derivation, acute data, with appropriate considerations of uncertainty, may be used when chronic data are not available. This approach takes all available information into account, particularly for older established medicines that may predate current regulatory requirements for environmental data, and consequently helps prioritize resources for environmental testing. The ERC approach has been applied to 30 of AstraZeneca's APIs. Merits of the approach are discussed together with opportunities for potential future refinement. Integr Environ Assess Manag 2012; 8: 320–330. © 2011 SETAC
Electron microscopy of phagocytosis in syphilis and yaws.

In view of the great importance of phagocytosis in protecting the body against infection and in producing antibodies, the authors paid particular attention to phagocytosis in their electron microscope studies of tissues obtained from hard chancres in rabbits with syphilis and from testicular membranes in rabbits with yaws. The nature of the phagocytosis by particular cells is described, as is the fate of the micro-organisms thus trapped. Our previous papers (Ovcinnikov and Delektorskij, 1969, 1970) reported on the interrelationship between treponemes and cellular elements. This paper represents a continuation of these studies. Phagocytosis is one of the most important factors in the body's defences against infection. According to the definition of the founder of the phagocytic theory, Mecnikov (1884), 'the human and animal organism uses phagocytosis for the resorption of tissue elements, blood, and exudates, and also for the destruction of microbes, including those which produce infectious diseases'. Phagocytosis should not be looked upon as the culmination of the struggle between microbe and macro-organism. It represents the beginning of that struggle, the nature of which depends on the immunological activity of the body and on the condition of the Treponema pallidum organism (its viability, the production of L-forms, encystment, etc.). In essence all our drugs prove efficient only when they interact with the protective mechanisms of the host. The subsequent work of destruction is carried out by the cells of the body. In the initial stages of an infection, phagocytosis plays an extremely important role in the transmission of antigenic information and in bringing immunological processes into play against the infection. As the syphilitic process develops, so the role of phagocytosis in the body's fight against the infection becomes more important, making a study of this
Atorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner

Maternal protein restriction in rats leads to endothelial dysfunction and decreased NO bioavailability in the offspring. Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) are recognized to have pleiotropic actions including increasing NO bioavailability and reducing inflammation and oxidative damage. This study assessed statin treatment on vascular function in a model of endothelial dysfunction, which is independent of dyslipidemia. Wistar rats were fed a control (18% casein) or protein-restricted (9% casein) diet throughout pregnancy. At weaning, a subset of the protein-restricted group was given atorvastatin (10 mg/kg per day) in the drinking water. At 145 days of age, offspring were euthanized by CO2 inhalation. Plasma samples were collected for markers of inflammation, vascular reactivity of the thoracic aorta, and small mesenteric arteries were assessed on the wire myograph, and tissues were snap frozen for molecular biology analysis. Thoracic aorta endothelial-dependent vasodilatation was attenuated in the male offspring from both protein-restricted groups compared with controls (P<0.05) but was similar in females (P value not significant). Endothelial-dependent dilatation of mesenteric arteries was attenuated in male and female protein-restricted offspring (P<0.05) and was corrected by atorvastatin. Maternal protein restriction increased plasma inflammatory markers granulocyte chemotactic protein, lipocalin-2, and &bgr;2-microglobulin in male and C-reactive protein in female offspring (P<0.05). Atorvastatin had no effect on inflammatory markers in the males but restored C-reactive protein to control levels in the females (P<0.05). Aortic and mesenteric artery mRNA levels of endothelial NO synthase, superoxide dismutase 1, and tumor necrosis factor-&agr; were unchanged. These data suggest that atorvastatin can restore endothelial function in this model, but its effects are gender specific and dependent on the vascular bed.
A dynamo model for axisymmetric and non-axisymmetric solar magnetic fields

More and more observations are showing a relatively weak, but persistent, non-axisymmetric magnetic field co-existing with the dominant axisymmetric field on the Sun. Its existence indicates that the non-axisymmetric magnetic field plays an important role in the origin of solar activity. A linear non-axisymmetric α 2 ‐ � dynamo model is derived to explore the characteristics of the axisymmetric (m = 0) and the first non-axisymmetric (m = 1) modes and to provide a theoretical basis with which to explain the ‘active longitude’, ‘flip-flop’ and other non-axisymmetric phenomena. The model consists of an updated solar internal differential rotation, a turbulent diffusivity varying with depth, and an α-effect working at the tachocline in a rotating spherical system. The difference between the α 2 ‐� and the α‐� models and
Effect of levosimendan on right ventricular systolic and diastolic functions in patients with ischaemic heart failure

Objectives: Levosimendan is a novel positive inotropic calcium sensitiser agent used in acute left heart failure. In this study, the effect of levosimendan on the right ventricular systolic and diastolic functions was evaluated by tissue Doppler comparing them with dobutamine in patients with ischaemic heart failure.
A Deployable 600-720GHz ALMA-TypeSideband-Separating Receiver Cartridge

We designed, built and tested a new ALMA-type dual polarization, sideband-separating (2SB) receiver cartridge for the 600–720 GHz band (ALMA Band 9). It meets all the major technical specifications, most of them with ample margin. Key performance results: SSB noise temperature typically 200 K or better, with a slight upturn to about 250 K at the upper band edge; image rejection typically better than 15 dB with a few inband excursions to about 13 dB; the IF pass-band ripple over any 2 GHz subband is about 3 dB. The four 4–12 GHz IF outputs provide a total of 32 GHz bandwidth. Two copies are produced initially, one for deployment in the SEPIA front-end at APEX (Chile), the second for the future LLAMA telescope situated in Argentina. Apart from being deployable instruments in their own right, the two receiver cartridges act as prototypes and demonstrators for a future upgrade of the ALMA Band 9 array. In addition, the new cartridges are designed in such a way (including heritage from the ALMA Band 5 receivers built in collaboration with GARD, Chalmers University of technology, Sweden) that other highfrequency bands above, say, 200 GHz could be implemented with relative ease in the existing structure. This would enable, for instance, the production of 230 GHz receivers for various projected observatories that aim to participate in the EventHorizon Telescope consortium.