Miracle-dz/UniFAR-FTUs huggingface dataset:
43.2 MUSCARINIC M1 RECEPTORS: INVOLVEMENT IN THE PATHOPHYSIOLOGY AND TREATMENT OF SCHIZOPHRENIA

Abstract Background Evidence from postmortem CNS studies and a neuroimaging study suggest that, compared to controls, there are low levels of muscarinic receptors in a number of CNS regions from subjects with schizophrenia. Current data suggests the muscarinic M1 receptor is lower in the cortex of subjects with schizophrenia but other muscarinic receptors may be decreased in sub-cortical regions such as the striatum and hippocampus. In addition, it has been reported that ~25% of subjects with schizophrenia can be divided into a distinct sub-group because they have a marked decrease in cortical muscarinic M1 receptors (muscarinic receptor deficit schizophrenia (MRDS)). These findings have become of clinical significance because proof of principal data shows that treating subjects with schizophrenia with drugs that activate the muscarinic M1 receptor is effective in lessening the symptoms associated with the disorder. Methods Published and unpublished data will be reviewed to challenge the hypothesis that drugs that activate the muscarinic M1 receptor will be useful in treating schizophrenia. Results A proof of clinical trial has shown that treating subjects with treatment resistant schizophrenia with the muscarinic M1 and 4 receptor agonist, xanomeline, improves positive and negative symptoms as well as cognitive deficits. Moreover, it has more recently been reported that giving xanomeline on a transdermal patch with a peripheral muscarinic receptor antagonist can lessen the unwanted side effects of the drug to that of placebo. Relevant to these data is the finding that there is a sub-group of subjects with MRDS as the absence of cortical muscarinic M1 receptors in these receptors may make these subjects resistant to treatment with muscarinic M1 receptor agonists. However, novel studies using postmortem CNS from subjects with MRDS and non-MRDS has shown that whilst subjects with MRDS will likely be resistant to muscarinic M1 receptor orthosteric agonists (oxotremorine-M) they will, at least partially, respond to muscarinic M1 receptor allosteric agonists (AC-42) or positive allosteric modulators (BQCA). Discussion Muscarinic receptor agonism appears to be a promising new treatment for schizophrenia. However, some subjects with MRDS may only respond to activation of the allosteric site on the muscarinic M1 receptor. Evidence from a neuroimaging study suggests subjects with MRDS can be identified whilst living. Hence, establishing the muscarinic receptor status of subjects involved in trials of muscarinic M1 receptor agonists may help in explaining varying levels of treatment responsiveness in subjects with schizophrenia. These conclusions, being directed by data from studies using postmortem CNS, reflect the need for drug discovery and delivery to be based on a growing understanding of the pathophysiology(ies) of schizophrenia.
MHC structure and function – antigen presentation. Part 1

The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function.
Ocena wpływu poliwinyloaminy na inhibitujące właściwości płuczki wiertniczej

Podczas przewiercania skał ilasto-łupkowych bardzo ważną kwestią jest zapobieganie ich hydratacji przy użyciu płuczek wiertniczych o działaniu inhibitującym. Podstawowym składnikiem takich płuczek są środki chemiczne pełniące funkcję inhibitorów hydratacji skał ilasto-łupkowych, jak KCl, PHPA, poliglikole oraz krzemiany: sodowy lub potasowy. Jak wykazały przeprowadzone w INiG – PIB badania laboratoryjne, rolę inhibitorów mogą pełnić również polimery zawierające pierwszorzędowe grupy aminowe (–NH2) bezpośrednio związane z atomami węgla w łańcuchu głównym. Przedstawicielem tych polimerów jest poliwinyloamina (PVAm), której syntezę przeprowadzono w warunkach laboratoryjnych przy użyciu N-winyloformamidu (NVF). Otrzymana PVAm o niskiej i wysokiej średniej masie molowej wykorzystana została do opracowania nowej odmiany płuczki inhibitowanej aminowo-glikolowej. Właściwości inhibitujące uzyskanej płuczki określono na podstawie badań dyspersji oraz pęcznienia wybranych skał ilasto-łupkowych. Otrzymane wyniki badań dowodziły wyższej efektywności jej inhibitującego oddziaływania na skały ilasto-łupkowe w porównaniu z płuczką stosowaną w warunkach otworowych zawierającą w składzie jonowo-polimerowy zestaw inhibitorów, tj. KCl-PHPA-PEG.
Blood–Brain Barrier Transport of Kynurenines: Implications for Brain Synthesis and Metabolism

Abstract: To evaluate the potential contribution of circulating kynurenines to brain kynurenine pools, the rates of cerebral uptake and mechanisms of blood–brain barrier transport were determined for several kynurenine metabolites of tryptophan, including L‐kynurenine (L‐KYN), 3‐hydroxykynurenine (3‐HKYN), 3‐hydroxyanthranilic acid (3‐HANA), anthranilic acid (ANA), kynurenic acid (KYNA), and quinolinic acid (QUIN), in pentobarbital‐anesthetized rats using an in situ brain perfusion technique. L‐KYN was found to be taken up into brain at a significant rate [permeability—surface area product (PA) = 2–3 × 10−3 ml/s/g] by the large neutral amino acid carrier (L‐system) of the blood–brain barrier. Best‐fit estimates of the Vmax and Km of saturable L‐KYN transfer equalled 4.5 × 10−4μmol/s/g and 0.16 μmol/ml, respectively. The same carrier may also mediate the brain uptake of 3‐HKYN as D,L‐3‐HKYN competitively inhibited the brain transfer of the large neutral amino acid L‐leucine. For the other metabolites, uptake appeared mediated by passive diffusion. This occurred at a significant rate for ANA (PA, 0.7–1.6 × 10−3 ml/s/g), and at far lower rates (PA, 2–7 × 10−5 ml/s/g) for 3‐HANA, KYNA, and QUIN. Transfer for KYNA, 3‐HANA, and ANA also appeared to be limited by plasma protein binding. The results demonstrate the saturable transfer of L‐KYN across the blood–brain barrier and suggest that circulating L‐KYN, 3‐HKYN, and ANA may each contribute significantly to respective cerebral pools. In contrast, QUIN, KYNA, and 3‐HANA cross the blood–brain barrier poorly, and therefore are not expected to contribute significantly to brain pools under normal conditions.
Different roles of flowering time genes in the activation of floral initiation genes in Arabidopsis.

We have analyzed double mutants that combine late-flowering mutations at four flowering-time loci (f E, FPA, F WA, and FT) with mutations at the LEAFY ( L N ) , APETALA7 (AP7), and TERMlNAL FLOWER7 (TFL7) loci involved in the floral initiation process (FLIP). Double mutants between f t -7 or fwa-7 and lfy-6 completely lack flowerlike structures, indicating that both F WA and F T act redundantly with LF Y to control AP7. Moreover, the phenotypes of f t 7 ap7-7 and fwa-7 ap7-7 double mutants are reminiscent of the phenotype of ap7-7 cal-7 double mutants, suggesting that FWA and F T could also be involved in the control of other FLlP genes. Such extreme phenotypes were not observed in double mutants between f v e d or fpa-7 and lfy-6 or ap7-7. Each of these showed a phenotype similar to that of ap7-7 or lfy-6 mutants grown under noninductive photoperiods, suggesting a redundant interaction with FLlP genes. Finally, the phenotype of double mutants combining the late-flowering mutations with tfH-2 were also consistent with the different roles of flowering-time genes.
Clocked CMOS adiabatic logic with integrated single-phase power-clock supply

The design and experimental evaluation of a clocked adiabatic logic (GAL) is described in this paper. CAL is a dual-rail logic that operates from a single-phase AC power-clock supply. This new low-energy logic makes it possible to integrate all power control circuitry on the chip, resulting in better system efficiency, lower cost, and simpler power distribution. CAL can also be operated from a DC power supply in a nonenergy-recovery mode compatible with standard CMOS logic. In the adiabatic mode, the power-clock supply waveform is generated using an on-chip switching transistor and a small external inductor between the chip and a low-voltage DC supply. Circuit operation and performance are evaluated using a chain of inverters realized in a 1.2 /spl mu/m CMOS technology. Experimental results show that energy savings are achieved at clock frequencies up to about 40 MHz as compared to the nonadiabatic mode. Since CAL can operate both in adiabatic and nonadiabatic modes, power management strategies may be based upon switching between modes when necessary.
Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology.

tools and the implementation programmes for the recommendations. The loop between clinical research, writing of guidelines, and implementing them into clinical practice can only be completed if surveys and registries are organized to verify that actual clinical practice is in keeping with what is recommended in the guidelines. Such surveys and registries also make it possible to check the impact of strict implementation of the guidelines on patient outcome. are suggested as a ﬁrst line anti-anginal therapy in patients without contraindications.
Book Review: Interpreting Motion: Grounded Representations for Spatial Language by Inderjeet Mani and James Pustejovsky

Inderjeet Mani and James Pustejovsky present a documentation of the state of the art with respect to the formal and computational representation of motion concepts expressed in language (mostly English). Starting from the conceptual properties rep- resented in the linguistic repertory of motion, they provide an overview of existing for- malisms and annotation approaches, ultimately moving towards automatic approaches and computational applications. The book is timely in its representation of the current understanding of motion concepts in language, and will therefore be of great interest in the computational and cognitive linguistics communities. Why, one may ask, do we need a better understanding of motion? It might seem that motion is just one of many human concepts expressed by a number of linguistic terms, which are adequately described by their lexical entries in anybody's dictionary. Mani and Pustejovsky's analysis of the linguistic representation of motion suggests a very different idea, however. Far from representing just one marginal aspect of human language, the conceptualization and verbalization of motion turns out to be central to human life—and, as a consequence, central to communication. Motion combines the two fundamental human concepts of space and time. Space without time is, for humans, as meaningless as time without space. Both are inextricably linked—and this link is most notably and systematically represented in language via expressions of motion. Motion is represented whenever aspects of life are described, reflecting its deep relevance for human thinking. Any computational approach towards interpreting natural language representation will, sooner or later, need to deal with motion concepts. Interpreting motion, therefore, turns out to be one of the most fundamental research issues for a variety of purposes both in basic (or cognitive) and applied (or computational) research.
Tight bounds on the redundancy of Huffman codes

A method for deriving optimal upper bounds on the redundancy of binary Huffman codes in terms of the probability p/sub 1/ of the most likely source letter is presented. This method will be used to compute bounds for all p/sub 1/>or=1/127, which were previously known only for a few special cases. Furthermore, the known optimal lower bound for binary Huffman codes is generalized to arbitrary code alphabets and some upper bounds for D-ary Huffman codes, 2 or=1/2. >
Pathology Working Group review of selected upper respiratory tract lesions in rats and mice.

The collected comments and pathologic diagnoses of several pathologists are summarized for 18 cases in which lesions were induced in the upper respiratory tract of rats and mice. Specific neoplastic and nonneoplastic lesions of the nose and trachea are described and discussed, and opinions regarding pathogenesis and biologic significance of the lesions are presented. The anatomic and pathophysiologic complexities of the rodent nose in relation to lesion development following inhalation or systemic exposure to xenobiotics are important considerations in the genesis of pathologic changes in this organ. ImagesPLATE 1.PLATE 2.PLATE 3.PLATE 4.PLATE 5.PLATE 6.PLATE 7.PLATE 8.PLATE 9.PLATE 10.PLATE 11.PLATE 12.PLATE 13.PLATE 14.PLATE 15.PLATE 16.PLATE 17PLATE 18PLATE 19PLATE 20.PLATE 21.PLATE 22.PLATE 23.PLATE 24.PLATE 25.PLATE 26.PLATE 27.PLATE 28.PLATE 29.PLATE 30.PLATE 31.PLATE 32.PLATE 33.PLATE 34.PLATE 35.PLATE 36.PLATE 37.PLATE 38.PLATE 39.PLATE 40.PLATE 41.PLATE 42.PLATE 43.PLATE 44.PLATE 45.PLATE 46.PLATE 47.PLATE 48.PLATE 49.PLATE 50.PLATE 51.PLATE 52.PLATE 53.
Write barrier removal by static analysis

We present a set of static analyses for removing write barriers in programs that use generational garbage collection. To our knowledge, these are the first analyses for this purpose. Our Intraprocedural analysis uses a flow-sensitive pointer analysis to locate variables that must point to the most recently allocated object, then eliminates write barriers on stores to objects accessed via one of these variables. The Callee Type Extension incorporates information about the types of objects allocated in invoked methods, while the Caller Context Extension incorporates information about the most recently allocated object at call sites that invoke the currently analyzed method. Results from our implemented system show that our Full Interprocedural analysis, which incorporates both extensions, can eliminate the majority of the write barriers in most of the programs in our benchmark set, producing modest performance improvements of up to 7% of the overall execution time. Moreover, by dynamically instrumenting the executable, we are able to show that for all but two of our nine benchmark programs, our analysis is close to optimal in the sense that it eliminates the write barriers for almost all store instructions observed not to create a reference from an older object to a younger object.
Support mechanisms to conduct empirical studies in software engineering

Context: Empirical studies are gaining recognition in the Software Engineering (SE) research community. In order to foster empirical research, it is essential understand the environments, guidelines, process, and other mechanisms available to support these studies in SE. Goal: Identifying the mechanisms used to support the empirical strategies adopted by the researches in the major Empirical Software Engineering (ESE) scientific venues. Method: We performed a systematic mapping study that included all full papers published at EASE, ESEM and ESEJ since their first editions. A total of 898 studies were selected. Results: We provide the full list of identified support mechanisms and the strategies that uses them. The most commonly mechanisms used to support the empirical strategies were two sets of guidelines, one to secondary studies and another to experiments. The most reported empirical strategies are experiments and case studies. Conclusions: The use of empirical methods in SE has increased over the years but many studies do not apply these methods nor use mechanisms to guide their research. Therefore, the list of support mechanisms, where and how they were applied is a major asset to the SE community. Such asset can foster empirical studies aiding the choice regarding which strategies and mechanisms to use in a research. Also, we identified new perspectives and gaps that foster the development of resources to aid empirical studies.
Run-time correlation engine for system monitoring and testing

Today's enterprise applications can produce vast amounts of information both during system testing and in production. Correlation of this information can be difficult as it is generally stored in a range of different event logs, the format of which can be application or vendor specific. Furthermore these large logs can be physically distributed across a number of different locations. As a result it can be difficult to form a coherent understanding of the overall system behaviour. This has implications for a number of domains (e.g. autonomic computing, system testers), where an understanding of the system behaviour at run-time is required (e.g. for problem determination, autonomic management etc.) This paper presents an approach and implementation of run-time correlation of large volumes of log data and symptom matching of known issues in the context of large enterprise applications. Our solution provides for automatic data collection, data normalisation into a common format, run-time correlation and analysis of the data to give a coherent view of system behaviour at run-time and a symptom matching mechanism that can identify known errors in the correlated data on the fly.
Pandemic (H1N1) 2009 Cases, Buenos Aires, Argentina

To determine clinical and virologic characteristics of pandemic (H1N1) 2009 in Buenos Aires, Argentina, we conducted real-time reverse transcription–PCR on samples from patients with influenza-like illness, June 11–30, 2009. Of 513 patients tested, 54% were positive for influenza virus subtype H1N1. Infection rate was lowest for patients ≥60 years of age.
Comparison of Growth Factor and Platelet Concentration From Commercial Platelet-Rich Plasma Separation Systems

Background: Clinical studies claim that platelet-rich plasma (PRP) shortens recovery times because of its high concentration of growth factors that may enhance the tissue repair process. Most of these studies obtained PRP using different separation systems, and few analyzed the content of the PRP used as treatment. Purpose: This study characterized the composition of single-donor PRP produced by 3 commercially available PRP separation systems. Study Design: Controlled laboratory study. Methods: Five healthy humans donated 100 mL of blood, which was processed to produce PRP using 3 PRP concentration systems (MTF Cascade, Arteriocyte Magellan, Biomet GPS III). Platelet, white blood cell (WBC), red blood cell, and fibrinogen concentrations were analyzed by automated systems in a clinical laboratory, whereas ELISA determined the concentrations of platelet-derived growth factor αβ and ββ (PDGF-αβ, PDGF-ββ), transforming growth factor β1 (TGF-β1), and vascular endothelial growth factor (VEGF). Results: There was no significant difference in mean PRP platelet, red blood cell, active TGF-β1, or fibrinogen concentrations among PRP separation systems. There was a significant difference in platelet capture efficiency. The highest platelet capture efficiency was obtained with Cascade, which was comparable with Magellan but significantly higher than GPS III. There was a significant difference among all systems in the concentrations of WBC, PDGF-αβ, PDGF-ββ, and VEGF. The Cascade system concentrated leukocyte-poor PRP, compared with leukocyte-rich PRP from the GPS III and Magellan systems. Conclusion: The GPS III and Magellan concentrate leukocyte-rich PRP, which results in increased concentrations of WBCs, PDGF-αβ, PDGF-ββ, and VEGF as compared with the leukocyte-poor PRP from Cascade. Overall, there was no significant difference among systems in the platelet concentration, red blood cell, active TGF-β1, or fibrinogen levels. Clinical Relevance: Products from commercially available PRP separation systems produce differing concentrations of growth factors and WBCs. Further research is necessary to determine the clinical relevance of these findings.
Modeling and evaluation of cycloconverter-fed, two-stator windings SAG mill drive. Part I: Modeling options

Typical drive configurations of high-capacity SAG mills uses a two-stator windings vector controlled synchronous motor, with 30o shift between the two windings, fed by a two secondary's delta-delta-wye power transformer and two 6-pulse cycloconverters. Paper presents and evaluates three different modeling options for the SAG mill drive. First option considers a complete model in phase and qd0 variables of the two-stator winding synchronous motor fed by two 6-pulse cycloconverters. The second option develops a winding rotation transformation to obtain an equivalent one-stator winding synchronous motor, which is fed by a 12-pulse cycloconverter. The third model considers the equivalent one-stator synchronous motor fed by an ideal converter that produces purely sinusoidal voltage and current waveforms. Each model is evaluated during steady state, and during step speed commands and step load disturbances. Responses are compared to field records of an 8.2 MW SAG mill, confirming the accuracy of the developed models.
Prevalence, Awareness, Treatment, and Control of Hypertension in China

Abstract—The objective of this study was to estimate the prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the general adult population in China. The International Collaborative Study of Cardiovascular Disease in ASIA (InterASIA), conducted in 2000–2001, used a multistage cluster sampling method to select a nationally representative sample. A total of 15 540 adults, age 35 to 74 years, were examined. Three blood pressure measurements were obtained by trained observers by use of a standardized mercury sphygmomanometer after a 5-minute sitting rest. Information on history of hypertension and use of antihypertensive medications was obtained by use of a standard questionnaire. Hypertension was defined as a mean systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, and/or use of antihypertensive medications. Overall, 27.2% of the Chinese adult population age 35 to 74 years, representing 129 824 000 persons, had hypertension. The age-specific prevalence of hypertension was 17.4%, 28.2%, 40.7%, and 47.3% in men and 10.7%, 26.8%, 38.9%, and 50.2% in women age 35 to 44 years, 45 to 54 years, 55 to 64 years, and 65 to 74 years, respectively. Among hypertensive patients, only 44.7% were aware of their high blood pressure, 28.2% were taking antihypertensive medication, and 8.1% achieved blood pressure control (<140/90 mm Hg). Our results indicate that hypertension is highly prevalent in China. The percentages of those with hypertension who are aware, treated, and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of hypertension in China.