Miracle-dz/UniFAR-FTUs huggingface dataset:
A Population Pharmacokinetic Analysis of Fimasartan, a Selective Angiotensin II Receptor Antagonist, in Healthy Caucasian Subjects and Korean Patients With Hypertension

A population pharmacokinetic (PK) model of fimasartan, a selective angiotensin II receptor antagonist, was developed and significant covariates for its PK parameters were identified using 1438 plasma concentrations from 69 subjects (aged 19–64 years, weighing 43.5–95.3 kg), enrolled in 2 phase I studies (n = 42, 96.4% Caucasian) and a phase II study (n = 27, Korean hypertensive patients). The nonlinear mixed‐effects analysis method by NONMEM was used, and the final model was qualified using sensitivity analysis, bootstrapping, and visual predictive checks. A two‐compartment open linear PK model with mixed zero‐ and lagged first‐order absorption best described observed plasma fimasartan concentrations. The typical value of the apparent clearance of fimasartan for those weighing 70 kg with total bilirubin of 0.7 mg/dL was 176 L/h (95% confidence interval: 163–189 L/h), and its interindividual and interoccasion variability as coefficient of variation was 26.9% (20.5–31.6%) and 10.5% (6.3–15.5%), respectively. Simulation of steady state concentrations indicated body weight was the most influential covariate on the exposure of fimasartan (i.e., lower level in heavier subjects). The population PK model of fimasartan should be refined as more studies are conducted in various clinical conditions.
SEXUAL SIZE DIMORPHISM AND TRANSITION TO PARASITISM IN COPEPODS

PONS, 0. , AND R. J. PETIT. 1995. Estimation, variance and optimal sampling of gene diversity. I. Haploid locus. Theor. Appl. Genet. 90:462-470. POWELL, W. , M. MORGANTE, R. McDEVITI, G. G. VENDRAMIN, AND J. A. RAFALSKI. 1995. Polymorphic simple sequence repeat regions in chloroplast genomes: Applications to the population genetics of pines. Proc. Nat. Acad. Sci. USA 92:7759-7763. REILLE, M. , AND J. J. LOWE. 1993. A re-evaluation of vegetation history of eastern Pyrenees (France) from the end of the last glacial to the present. Q. Sci. Rev. 12:47-77. SCHAFFALISTZKY DE MUCKADELL, M. 1955. A development stage in Fagus sylvatica L. characterized by abundant flowering. Physiol. Plant. 8:370-373.
Fault-Tolerant Control design using a virtual sensor for LPV systems

In this paper, a Fault Tolerant Control (FTC) strategy using a virtual sensor for Linear Parameter Varying (LPV) systems is proposed. The main idea of this FTC method is to reconfigure the control loop such such that the nominal controller could be still used without need of retuning it. That is, the plant with the sensor fault is modified adding the virtual sensor block that masks this fault and allows the controller to see the same plant as before the fault. This virtual sensor is designed using polytopic LPV techniques and Linear Matrix Inequalities (LMIs). The LPV state feedback controller is designed for quadratic H2/H∞ performance using a polytopic representation of the system that leads to solve a finite number of algebraic LMIs. To assess the performance of the proposed approach a two degree of freedom helicopter is used.
Woronin bodies, their impact on stress resistance and virulence of the pathogenic mould Aspergillus fumigatus and their anchoring at the septal pore of filamentous Ascomycota

Hyphae of filamentous Ascomycota consist of compartments that are connected via septal pores. To avoid a dramatic loss of cellular content after wounding, fungi developed mechanisms to occlude their septal pores. In most Pezizomycotina, so‐called Woronin bodies are anchored in proximity to the pore. This is a prominent example for precise spatial positioning of organelles, but so far the underlying molecular organization has remained largely unknown. Using the pathogenic mould Aspergillus fumigatus, we provide evidence that Woronin bodies are important for stress resistance and virulence. Furthermore the molecular machinery anchoring them at the septum is described. Namely, we have identified Lah as the tethering protein and provide evidence that the Woronin body protein HexA binds to the septal pore in a Lah‐dependent manner. Moreover, we demonstrate that a striking poly‐histidine motif targets HexA to the septal cell wall. Thus, the axis HexA‐Lah is an excellent candidate for the tether linking Woronin bodies to the septum. This model applies to A. fumigatus, but most likely also to the vast majority of the Pezizomycotina. Our findings shed light on the evolution of Woronin body anchoring and provide a basis for the development of novel strategies to combat fungal pathogens like A. fumigatus.
The Boskin Commission Report After a Decade: After-life or Requiem?

The author provides a political economy interpretation of the rise and fall of public interest in price measurement, placing these developments in the context of the attempt by Congress and the White House to deal with growing deficits in the early to mid-1990s. He provides a detailed discussion of initiatives since the Boskin Commission, such as the National Academy of Sciences panel, to improve CPI measurement. The author examines the thorny issue of the CPI for health care, with particular reference to the Boskin Commission recommendation that BLS move from pricing health care inputs to pricing health care outcomes. He concludes that the BLS has responded constructively to the recommendations from the various price measurement initiatives. By implementing many of the methodological changes suggested, the BLS has reduced net CPI inaccuracy and increased professional confidence in the reliability of the CPI.
Frequency, Causes, and New Challenges of Indeterminate Results in Western Blot Confirmatory Testing for Antibodies to Human Immunodeficiency Virus

More than 2 decades of developments in the field have led to a wide variety of test kits available for addressing the different needs of surveillance, diagnosis, and monitoring of human immunodeficiency virus (HIV) infection and antiretroviral therapy ([20][1], [23][2]). These test kits are based on
Native human neocortex release‐regulating dopamine D2 type autoreceptors are dopamine D2 subtype

Dopamine (DA) autoreceptors expressed at DA nerve terminals regulate DA release. Considerable evidence has indicated that, in rodents, these autoreceptors belong to the D2 type of the DA receptor family, which, in turn, comprises the D2, D3 and D4 subtypes. We investigated here, for the first time, the subclassification of native human DA autoreceptors by studying the release of [3H]DA evoked by electrical stimulation in fresh human neocortical slices. The results have been compared with those obtained in three animal systems: rat neocortical and striatal slices and rat mesencephalic neuronal cultures. In human neocortical slices, the D2/D3 receptor agonist quinpirole (1 n m–10 μm) inhibited tritium release with a calculated EC50 of 17 n m and a maximal inhibition of ≈ 75% reached at 1 μm. In the presence of the D2/D3 receptor antagonist (–)‐sulpiride (0.1 and 1 μm), the concentration–response curve of quinpirole was shifted to the right, and the apparent pA2 mean value was 8.5 (8.14–8.77); on the other hand, the inhibitory effects of quinpirole were not affected by the D3 receptor‐selective antagonist [7‐N,N‐dipropylamino‐5,6,7,8‐tetrahydro‐naphtho(2,3b) dihydro,2,3‐furane] (S 14297) and the D4 receptor‐selective antagonist 3‐(4‐[4‐chlorophenyl]piperazin‐1‐yl)‐methyl‐1H‐pyrrolo [2,3‐b]pyridine (L‐745,870) (0.01–1 μm in each case). Superimposable results have been obtained when the release was elicited from rat striatal slices or dopamine mesencephalic neurons in culture, whereas quantitative differences emerged in the case of rat cortical slices. It is concluded that in human brain, as well as in rat brain, the release of DA in the terminal region of midbrain dopaminergic neurons is regulated through autoreceptors of the D2 subtype.
Spatial response properties of contralateral inhibited lobula plate tangential cells in the fly visual system

This study describes the spatial response properties of a particular group of motion‐sensitive and directionally selective neurons located in the lobula plate of the fly visual system. Their preferred motion direction is front‐to‐back (depolarization), and their null direction is back‐to‐front (hyperpolarization). They receive inhibitory input from the contralateral eye during pattern motion from back to front (regressive). In this study, we call these neurons regressive contralateral inhibited lobula plate tangential cells (rCI‐LPTCs). Three physiologic groups of rCI‐neurons (rCI‐I, rCI‐IIa, and rCI‐IIb) can be distinguished on the basis of their ipsilateral pattern size dependence and their inhibitory contralateral input. rCI‐I neurons depolarize during the motion of small ipsilateral patterns from front to back, but they become hyperpolarized by large ipsilateral patterns moving in the same direction. rCI‐IIa and rCI‐IIb neurons receive bidirectional inhibitory input from the contralateral eye. rCI‐IIa neurons respond best to small ipsilateral pattern sizes, but unlike rCI‐I neurons, their net response to large patterns is positive. rCI‐IIb neurons respond best to large ipsilateral patterns. The anatomical and physiologic variability of the rCI‐neurons suggests that more than three types of rCI‐neurons exist. The suggested physiologic groups might be preliminary. We recorded one neuron that could mediate the bidirectional inhibitory input that rCI‐IIa and rCI‐IIb neurons receive from the contralateral eye. In the case of the rCI‐IIa neurons at least one further contralateral inhibitory element has to be assumed. The tuning of rCI‐IIa neurons to small ipsilateral pattern sizes is likely to be based on an on‐center/off‐surround organization of their synaptic input. J. Comp. Neurol. 406:51–71, 1999. © 1999 Wiley‐Liss, Inc.
Switching to quetiapine in patients with acute mania who were intolerant to risperidone

This study evaluated the overall efficacy and tolerability of quetiapine in the treatment of inpatients with acute mania who are intolerant to risperidone in combination with a mood stabilizer. Eighteen patients completed this 3‐week trial. The efficacy and tolerability was assessed upon admission, at baseline, and 1 and 3 weeks later. The Young mania rating scale (YMRS) and clinical global impression‐severity (CGI‐s) scores from the baseline to the endpoint, decreased by 39.8% and 40.0%, respectively. Fifteen (78.9%) and 18 (94.7%) patients exhibited at least a 50% improvement in the YMRS and CGI‐s scores by the end of the trial. Measurements taken through the Barnes akathisia rating scale (BARS), the Simpson‐Angus rating scale (SARS) and the drug attitude inventory shortened version‐10 (DAI‐10) also showed significant improvement.
Onset of carbon isotope excursion at the Paleocene-Eocene thermal maximum took millennia, not 13 years

The Paleocene-Eocene thermal maximum (PETM) may represent the best paleo-analog for rapid and massive carbon release to the ocean and atmosphere. Thus, constraining the carbon release rate at its onset is critical. Wright and Schaller (1) use records from apparently rhythmically layered shelf sediments to argue that the layering is annual and that the onset of the carbon isotope excursion (CIE, fingerprint for carbon release) in the surface ocean was complete in 13 y. Using basic carbon cycle and climate considerations, we show this is not feasible. In fact, Wright and Schaller’s isotope records indicate that the CIE onset took at least several millennia. This finding rules out a cometary origin of the carbon release.
Rapid method for detection of Coxiella burnetii antibodies using high-density particle agglutination

A high-density particle agglutination test, using erythrocyte-sensitizing substance from phase II Coxiella burnetii adsorbed to high-density composite particles, was developed for rapid serodiagnosis of Q fever. The test was compared with the microimmunofluorescence test for sensitivity and specificity by using 3,036 human serum samples collected in Gifu Prefecture, Japan. An excellent agreement was found between the two tests for the acute-phase group and paired serum samples, but some discordant results were observed in the single-sample group. The sensitivity and specificity of the high-density particle agglutination test were both 100% in the former group and 81.6 and 99.9%, respectively, in the latter group. The test is a very promising tool for routine serodiagnosis of Q fever because of its simplicity, sensitivity, and specificity.
Memory IL‐22‐producing CD4+ T cells specific for Candida albicans are present in humans

Co‐expression of IL‐22 and IL‐17 has been identified and demonstrated to be involved in the immunopathogenesis of some autoimmune diseases as well as the defense against pathogenic infections in animal studies. However, the properties of IL‐22‐producing cells in humans remain largely unclear. In the present study, we showed that IL‐22 could be induced from human PBMC following various polyclonal stimulations. The majority of IL‐22‐producing cells in PBMC were CD4+ T cells with a memory cell phenotype. In addition, we found that a subset of IL‐22+ T cells produced IL‐22 alone, whereas other IL‐22+ T cells co‐expressed cytokines typical of Th1, Th2 and Th17 cells. Importantly, stimulation of PBMC from healthy adults with heat‐inactivated Candida albicans (C. albicans) yeast or hyphae resulted in IL‐22 production by central and effector memory CD4+ T cells. Moreover, CD4+CCR6+ but not CD4+CCR6− T cells produced IL‐22 when stimulated with either C. albicans or PMA and ionomycin. In addition, PBMC from the individuals infected with C. albicans produced a significantly higher amount of IL‐22 compared with healthy controls following stimulation with C. albicans. These data demonstrate that IL‐22‐producing T cells in humans may play an important role in the defense against fungal infections such as C. albicans.
Management of bile duct tumors

Cholangiocarcinomas are a rare but highly fatal disease. The only curative treatment is radical surgical resection of the tumor and the regional lymph nodes. More than half of patients have irresectable disease, which implicates a median survival of < 1 year. The mainstay of palliative treatment is endoscopic or percutaneous drainage of the biliary system. In patients with good performance status, palliative chemotherapy seems to provide some survival benefit together with an improved quality of life. No standard chemotherapy has been defined but gemcitabine monotherapy or the combination of gemcitabine with platin derivates or capecitabine seems to be more effective than other protocols. Additionally, photodynamic therapy has shown promising results and radiation might be helpful for localized disease. In a very selected population liver transplantation can also be an option.
Coffee, alcohol, smoking and cancer of the pancreas: A case‐control study

A hospital case control study on smoking, alcohol and coffee consumption as risk factors for pancreatic cancer, in which 161 cases were matched to 268 control patients, was conducted in France between 1982 and 1985. The results showed no association between tobacco or alcohol consumption and cancer of the pancreas, whereas coffee consumption was associated with an increased risk [OR of 2 or more cups per day vs. less: 2.27 (1.11–4.64) and 1.45 (0.82–2.55) among females and males respectively]. A dose‐response relationship was observed with coffee consumption in both sexes, stronger among females than among males: the linear increase estimates were 2.00 (1.22–3.29) and 1.32 (0.91–1.92) respectively. No interaction was found between coffee and tobacco, whereas the effect of coffee appeared to be limited to non‐drinkers of alcohol.
Characterization of the effects of the human dura on macro- and micro-electrocorticographic recordings

Objective. Electrocorticography (ECoG) electrodes implanted on the surface of the brain have recently emerged as a potential signal platform for brain–computer interface (BCI) systems. While clinical ECoG electrodes are currently implanted beneath the dura, epidural electrodes could reduce the invasiveness and the potential impact of a surgical site infection. Subdural electrodes, on the other hand, while slightly more invasive, may have better signals for BCI application. Because of this balance between risk and benefit between the two electrode positions, the effect of the dura on signal quality must be determined in order to define the optimal implementation for an ECoG BCI system. Approach. This study utilized simultaneously acquired baseline recordings from epidural and subdural ECoG electrodes while patients rested. Both macro-scale (2 mm diameter electrodes with 1 cm inter-electrode distance, one patient) and micro-scale (75 µm diameter electrodes with 1 mm inter-electrode distance, four patients) ECoG electrodes were tested. Signal characteristics were evaluated to determine differences in the spectral amplitude and noise floor. Furthermore, the experimental results were compared to theoretical effects produced by placing epidural and subdural ECoG contacts of different sizes within a finite element model. Main results. The analysis demonstrated that for micro-scale electrodes, subdural contacts have significantly higher spectral amplitudes and reach the noise floor at a higher frequency than epidural contacts. For macro-scale electrodes, while there are statistical differences, these differences are small in amplitude and likely do not represent differences relevant to the ability of the signals to be used in a BCI system. Conclusions. Our findings demonstrate an important trade-off that should be considered in developing a chronic BCI system. While implanting electrodes under the dura is more invasive, it is associated with increased signal quality when recording from micro-scale electrodes with very small sizes and spacing. If recording from larger electrodes, such as traditionally used clinically, the signal quality of epidural recordings is similar to that of subdural recordings.
A casual semantics for Logic Programming

En esta tesis, extendemos algunas de las principales semanticas de programacion logica, de manera que la informacion causal asociada con un atomo sea incluida en los modelos de cada programa logico. Tecnicamente, nuestra aproximacion consiste en una semantica multivaluada donde cada atomo esta asociado con sus causas en lugar de con un simple valor de verdad, verdadero o falso. Estas causas estan representadas por valores causales: conjuntos de graficos incomparables entre si que forman un reticulo completamente distributivo. Los valores causales pueden ser utiles para proporcionar justificaciones que expliquen por que un atomo dado es cierto en un modelo. Sin embargo, la caracteristica mas interesante es que estos valores puedan ser inspeccionados en el cuerpo de las reglas del programa por un nuevo tipo de literal causal, lo que permite, por ejemplo, razonar con enunciados de la forma "A ha causado B:' En concreto, definimos semanticas causales que son extensiones de la leasl model, la well-founded model, la slable model y la answer sel semanlics y demostramos que, para varios de los problemas causales que investigamos, el razonamiento en estas semanticas no es computacionalmente mas costoso que en sus correspondientes versiones estandar. Tambien proporcionamos metodos y herramientas para el calculo de las soluciones de diversas tareas de razonamiento bajo estas semanticas y mostramos como pueden ser utiles para la representacion de algunos de los ejemplos tradicionales de la literatura. El apendice e contiene un resumen extendido en castellano.
CONSUMPTION OF ULVA LACTUCA (CHLOROPHYTA) BY THE OMNIVOROUS MUD SNAIL ILYANASSA OBSOLETA (SAY)

Marine invertebrate grazing on temperate macroalgae may exert a significant “top‐down” control on macroalgal biomass. We conducted two laboratory experiments to test (1) if consumption by the omnivorous mud snail Ilyanassa obsoleta (Say) on the macroalga Ulva lactuca Linnaeus was a function of food quality (nitrogen content) and (2) if grazing on benthic macroalgae occurred at significant rates in the presence of alternative food sources in the sediment (detritus, larvae, benthic microalgae). Grazing rates were higher for N‐enriched macroalgae; however, all snails lost weight when grazing on macroalgae alone, indicating that U. lactuca was a poor food source. The presence of sediment from two sites, a sandy lagoon and an adjacent organic‐rich muddy tidal creek, did not affect consumption of macroalgae in microcosm experiments, and the grazing snails were capable of significantly reducing macroalgal biomass associated with both sediment types. Grazing rates by this omnivore were as high as 10.83 mg wet weight·individuals−1·d−1 and were similar to those recorded for herbivorous species. In situ loss rates calculated from average grazing rates per individual and snail abundances (up to 3.5 g dry weight·m−2·d−1) also were comparable with those calculated for herbivorous species. This level of grazing could remove up to 88% of new macroalgal growth at the lagoon site where the N supply was relatively low but had a much smaller effect (18% of new growth) at the high‐nutrient creek site. Snails facilitated macroalgal growth at both sites by increasing tissue N content by 40%–80%. Consumption and digestion of macroalgae aided in the recycling of nutrients temporarily bound in the algae and resulted in enrichment of surficial sediments. Increased N sequestration in the sediments also was associated with an interruption of snail burrowing behavior due to persistent anoxia in sediments rich in decaying algal material. Our data suggest that in shallow lagoons where mud snails and benthic macroalgae coexist, grazing may influence N retention in macroalgal biomass.
[Gynecological malignant tumor related multiple primary malignant neoplasms: clinical analysis of 30 cases].

OBJECTIVE To investigate the clinical features of gynecological malignant tumor related multiple primary malignant neoplasms (MPMN). METHODS Apply retrospective and comprehensive analysis to the clinical data of 30 patients with gynecological malignant tumor related MPMN. RESULTS Synchronous MPMN were found in 9 patients. Their average age was 50.2 years old and their median age was 49 years old. The neoplasms were located at ovary, uterus, cervix, breast and intestine. Metachronous MPMN were found in 21 patients. Their average age was 57.7 and their median age was 57 years old. The median interval between the first and the second primary malignant neoplasm was 4.0 years. The neoplasms were located at breast, ovary, uterus, gastrointestinal tract, uterine cervix, lung etc. In 30 cases, 26 of them were treated by surgical operation and further adjunctive treatment of chemotherapy and (or) radiotherapy was conducted as per the neoplasm staging and its pathological results. The rest 4 patients (first primary malignant neoplasms were excised from 3 of them and another one was not treated by surgical operation) received adjunctive treatment of chemotherapy and (or) radiotherapy. Followed ups, which varied from 6 to 60 months, were made to 29 patients and 20 out of the 29 were alive.5-year survival rate of patients with gynecological malignant tumor related MPMN was 47.8%, 2-year survival rate was 73.9%, and 1-year survival rate was 88.6%. CONCLUSION Pay more attention to the patients with gynecological malignant tumor related MPMN, examine the high-risk patients with malignant tumor comprehensively, identify whether it is recurrence, metastasis or new growth of malignant neoplasm, and further ensure early diagnosis and proper treatment, avoiding misdiagnosis and missed diagnosis.