julilili42/papers huggingface dataset:
Reassessing optimal neural population codes with neurometric functions
2011-02-28

Cortical circuits perform the computations underlying rapid perceptual decisions within a few dozen milliseconds with each neuron emitting only a few spikes. Under these conditions, the theoretical analysis of neural population codes is challenging, as the most commonly used theoretical tool—Fisher information—can lead to erroneous conclusions about the optimality of different coding schemes. Here we revisit the effect of tuning function width and correlation structure on neural population codes based on ideal observer analysis in both a discrimination and a reconstruction task. We show that the optimal tuning function width and the optimal correlation structure in both paradigms strongly depend on the available decoding time in a very similar way. In contrast, population codes optimized for Fisher information do not depend on decoding time and are severely suboptimal when only few spikes are available. In addition, we use the neurometric functions of the ideal observer in the classification task to investigate the differential coding properties of these Fisher-optimal codes for fine and coarse discrimination. We find that the discrimination error for these codes does not decrease to zero with increasing population size, even in simple coarse discrimination tasks. Our results suggest that quite different population codes may be optimal for rapid decoding in cortical computations than those inferred from the optimization of Fisher information.
The patients' perception of prodromal symptoms before the initial diagnosis of Parkinson's disease
2011-03-01

Abstract Background: Before the occurrence of motor symptoms permits the clinical diagnosis of Parkinson's disease (PD), about or even more than 50% of the dopaminergic neurons of the substantia nigra have degenerated. This time be called the prodromal phase of PD. Objective: To evaluate the time span from onset of first prodromal symptoms to the initial diagnosis of PD as well as the order of symptom occurrence. Methods: Retrospective study of 93 consecutively interviewed PD patients without dementia and 93 sex and age matched controls free of neurodegenerative disorders. A standardized in‐house telephone worksheet assessing 19 nonmotor and six early motor signs was used. Results: A total of 98.8% of all patients interviewed reported to have experienced prodromal symptoms prior to receiving the initial diagnosis of PD. Patients noticed an average of 7.6 different symptoms during this time interval. The mean time span between the recalled onset of any one symptom and PD diagnosis was 10.2 years. In both groups, the course of prodromal sign onset was associated with early neuropathological disease stages proposed by Braak. Outlook: These retrospectively gathered data confirm the existence of a long prodromal phase for PD that is consistent with neuropathological staging. A standardized questionnaire assessing such early symptoms may be helpful in identifying subjects at high risk for PD while they are still in the prodromal phase of the disorder. © 2011 Movement Disorder Society
Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis
2011-03-01

Abstract Introduction Sepsis has been identified as a risk factor for human cytomegalovirus (CMV) reactivation in critically ill patients. However, the contribution of CMV reactivation on morbidity and mortality is still controversial. Therefore, we analyzed the incidence and impact of CMV reactivation on outcome in patients with severe sepsis. Methods In a prospective longitudinal double-blinded observational study, 97 adult nonimmunosuppressed CMV-seropositive patients with new onset of severe sepsis were included. Leukocytes, plasma and tracheal secretions were examined weekly for CMV-DNA by PCR. Tracheal secretions were additionally tested for HSV (Herpes Simplex Virus)-DNA. The influence of CMV-reactivation on the endpoints was analysed by Cox proportional-hazard regression analysis. Time-dependency was evaluated by landmark analysis. Results Six out 97 died and five were discharged from the hospital within 72 hours and were excluded of the analysis. CMV reactivation occurred in 35 of the 86 (40.69%) analysed patients. HSV infection occurred in 23 of the 35 (65.7%) CMV reactivators. In 10 patients CMV-plasma-DNAemia appeared with a DNA-content below 600 copies/ml in four cases and a peak amount of 2,830 copies/ml on average. In patients with and without CMV reactivation mortality rates were similar (37.1% vs. 35.3%, P = 0.861), respectively. However, in the multivariate COX regression analyses CMV reactivation was independently associated with increased length of stay in the ICU (30.0, interquartile range 14 to 48 vs. 12.0, interquartile range 7 to 19 days; HR (hazard ratio) 3.365; 95% CI (confidence interval) 1.233 to 9.183, P = 0.018) and in the hospital (33.0, interquartile range 24 to 62 vs. 16.0, interquartile range 10 to 24 days, HR 3.3, 95% CI 1.78 to 6.25, P &lt; 0.001) as well as prolonged mechanical ventilation (22.0, interquartile range 6 to 36 vs. 7.5, interquartile range 5 to 15.5 days; HR 2.6,CI 95% 1.39 to 4.94; P &lt; 0.001) and impaired pulmonary gas exchange (six days, interquartile range 1 to 17, vs. three, interquartile range 1 to 7, days in reactivators vs. non-reactivators, P = 0.038). HSV reactivation proved not to be a risk factor for these adverse effects. Conclusions These data indicate an independent correlation between CMV reactivation and increased morbidity in the well-defined group of nonimmunosuppressed patients with severe sepsis, but CMV reactivation had no impact on mortality in this group with low CMV-DNA plasma levels. Thus, the potential harms and benefits of antiviral treatment have to be weighed cautiously in patients with severe sepsis or septic shock.
Hypoxia-Inducible Factor-1α–Dependent Protection from Intestinal Ischemia/Reperfusion Injury Involves Ecto-5′-Nucleotidase (CD73) and the A2B Adenosine Receptor
2011-03-01

Abstract Intestinal ischemia/reperfusion injury (IR) is characterized by intermittent loss of perfusion to the gut, resulting in dramatic increases in morbidity and mortality. Based on previous studies indicating an anti-inflammatory role for hypoxia-inducible factor (HIF)-1–elicited enhancement of extracellular adenosine production via ecto-5′-nucleotidase (CD73) and signaling through the A2B adenosine receptor (A2BAR), we targeted HIF-1 during IR using pharmacological or genetic approaches. Initial studies with pharmacological HIF activation indicated attenuation of intestinal injury with dimethyloxallyl glycine (DMOG) treatment during murine IR. Although DMOG treatment was associated with induction of CD73 transcript and protein, DMOG protection was abolished in cd73−/− mice. Similarly, DMOG treatment enhanced A2BAR transcript and protein levels, whereas DMOG protection was abolished in A2BAR−/− mice. Finally, studies of mice with conditional HIF-1α deletion in intestinal epithelia or pharmacological inhibition of HIF-1 with 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin revealed enhanced tissue injury during IR. These studies indicated a tissue-protective role of HIF-dependent enhancement of intestinal adenosine generation and signaling during intestinal IR.
The Mechanisms of HAMP-Mediated Signaling in Transmembrane Receptors
2011-03-01

HAMP domains mediate signal transduction in over 7500 enzyme-coupled receptors represented in all kingdoms of life. The HAMP domain of the putative archaeal receptor Af1503 has a parallel, dimeric, four-helical coiled coil structure, but with unusual core packing, related to canonical packing by concerted axial rotation of the helices. This has led to the gearbox model for signal transduction, whereby the alternate packing modes correspond to signaling states. Here we present structures of a series of Af1503 HAMP variants. We show that substitution of a conserved small side chain within the domain core (A291) for larger residues induces a gradual transition in packing mode, involving both changes in helix rotation and bundle shape, which are most prominent at the C-terminal, output end of the domain. These are correlated with activity and ligand response in vitro and in vivo by incorporating Af1503 HAMP into mycobacterial adenylyl cyclase assay systems.
Root plasticity buffers competition among plants: theory meets experimental data
2011-03-01

Morphological plasticity is a striking characteristic of plants in natural communities. In the context of foraging behavior particularly, root plasticity has been documented for numerous species. Root plasticity is known to mitigate competitive interactions by reducing the overlap of the individuals' rhizospheres. But despite its obvious effect on resource acquisition, plasticity has been generally neglected in previous empirical and theoretical studies estimating interaction intensity among plants. In this study, we developed a semi-mechanistic model that addresses this shortcoming by introducing the idea of compensatory growth into the classical-zone-of influence (ZOI) and field-of-neighborhood (FON) approaches. The model parameters describing the belowground plastic sphere of influence (PSI) were parameterized using data from an accompanying field experiment. Measurements of the uptake of a stable nutrient analogue at distinct distances to the neighboring plants showed that the study species responded plastically to belowground competition by avoiding overlap of individuals' rhizospheres. An unexpected finding was that the sphere of influence of the study species Bromus hordeaceus could be best described by a unimodal function of distance to the plant's center and not with a continuously decreasing function as commonly assumed. We employed the parameterized model to investigate the interplay between plasticity and two other important factors determining the intensity of competitive interactions: overall plant density and the distribution of individuals in space. The simulation results confirm that the reduction of competition intensity due to morphological plasticity strongly depends on the spatial structure of the competitive environment. We advocate the use of semi-mechanistic simulations that explicitly consider morphological plasticity to improve our mechanistic understanding of plant interactions.
Changing levels of circulating tumor cells in monitoring chemotherapy response in patients with metastatic breast cancer.
2011-03-01

The observation of changes in CTC level during the course of chemotherapy is useful in monitoring therapy efficacy and is correlated with overall survival. Further prospective trials should investigate the clinical usefulness of determining changes in CTC level during chemotherapy of MBC.
Phase I randomized dose-ascending placebo-controlled trials of ferroquine - a candidate anti-malarial drug - in adults with asymptomatic Plasmodium falciparum infection
2011-03-01

Abstract Background The development and spread of drug resistant Plasmodium falciparum strains is a major concern and novel anti-malarial drugs are, therefore, needed. Ferroquine is a ferrocenic derivative of chloroquine with proven anti-malarial activity against chloroquine-resistant and -sensitive P. falciparum laboratory strains. Methods Adult young male aged 18 to 45 years, asymptomatic carriers of P. falciparum , were included in two-dose escalation, double-blind, randomized, placebo-controlled Phase I trials, a single dose study and a multiple dose study aiming to evaluate oral doses of ferroquine from 400 to 1,600 mg. Results Overall, 54/66 patients (40 and 26 treated in the single and multiple dose studies, respectively) experienced at least one adverse event, 15 were under placebo. Adverse events were mainly gastrointestinal symptoms such as abdominal pain (16), diarrhoea (5), nausea (13), and vomiting (9), but also headache (11), and dizziness (5). A few patients had slightly elevated liver parameters (10/66) including two patients under placebo. Moderate changes in QTc and morphological changes in T waves were observed in the course of the study. However, no adverse cardiac effects with clinical relevance were observed. Conclusions These phase I trials showed that clinically, ferroquine was generally well-tolerated up to 1,600 mg as single dose and up to 800 mg as repeated dose in asymptomatic young male with P. falciparum infection. Further clinical development of ferroquine, either alone or in combination with another anti-malarial, is highly warranted and currently underway.
Spinocerebellar ataxia type 15: diagnostic assessment, frequency, and phenotypic features
2011-03-01

Background To guide time- and cost-efficient analyses of the increasing number of autosomal-dominant spinocerebellar ataxia genes (SCAs), more information about frequency distributions, phenotypic characteristics and optimal diagnostic strategies is warranted. Objective To assess the prevalence and phenotypic spectrum of SCA15 and to confirm multiplex ligation-dependent probe amplification (MLPA) as a robust and efficient strategy for routine molecular diagnosis. Methods Fifty-six German SCA families negative for common repeat expansions were screened for ITPR1 deletions by MLPA. Samples with conspicuous MLPA data were additionally assessed by high-density single nucleotide polymorphism (SNP) array to confirm MLPA results and further determine the size of deletions. The phenotype of patients harbouring ITPR1 deletions was characterised by standardised clinical, electrophysiological and imaging assessment. Results SCA15 accounted for 8.9% (5/56) of SCA families negative for common SCA repeat expansions. All deletions detected by MLPA were confirmed by SNP array. One of the ITPR1 deletions preserved exons 1 and 2 in the 5′ prime UTR of the ITPR1 gene. All patients with SCA15 (n=10) presented with slowly progressive cerebellar ataxia and vermal cerebellar atrophy, while clinical and electrophysiological signs of extracerebellar affection were mild and more variable. Conclusions SCA15 is the most common non-trinucleotide repeat SCA in Central Europe. Screening for ITPR1 deletions should be considered in patients with slowly progressive SCA, vermal cerebellar atrophy and prominent tremor after excluding common SCA repeat expansions. Promoter and exon 2 of ITPR1 may be preserved from the deletion in some cases of SCA15.
The Ties that do not Bind: The Union for the Mediterranean and the Future of Euro-Arab Relations
2011-03-01

What impact does the Union for the Mediterranean (UfM) have on the future evolution of Euro-Arab relations? This contribution first reflects on Arab reactions to the UfM, and subsequently analyses what alterations the UfM brings to existing Euro-Arab relations in terms of actors, institutional arrangements, and policy contents. In sum, the UfM caters well to Arab regimes’ priorities, namely the maintenance of authoritarian rule: The UfM tends to exclude societal voices and leads to a re-governmentalization of relations; the institutional set-up elevates Arab regimes to become formal veto-players, and the prioritized policy areas have – from an Arab regime perspective – the advantage of being de-politicized and stripped of any ambitious macro-political goals such as democratization. The UfM can thus be considered a triple victory for authoritarian Arab rulers in re-shaping their relations with Europe, and casts serious doubts on the hypothesis of the EU acting as a norm entrepreneur.
Sex-related differences in foot shape of adult Caucasians – a follow-up study focusing on long and short feet
2011-03-01

The study's purpose was to substantiate findings on sex-related differences in foot morphology focusing on fringe sizes. Altogether, 287 Caucasian adults with long or short feet were scanned. Data were analysed together with data from 847 subjects from a previous study with comparable inclusion criteria and anthropometric data by: (1)comparing absolute measures within 237-277 mm foot length (FL); (2) comparing averaged measures across sizes in % of foot length for 203-323 mm FL; (3) reclassifying the additional subjects into a previously defined foot type classification. Male feet were wider and higher for the same FL. Averaged across sizes, no relevant differences between sexes were found for widths and heights. Slender or flat-pointed foot types were more common in longer feet, shorter feet tended to be bigger. Definitions for 'long' and 'short' are sex-related with an offset of three shoe sizes (EU). Results of this follow-up study on long and short feet can substantiate previous findings mainly described for the most common sizes. STATEMENT OF RELEVANCE: Improper footwear can cause pain and injury and proper fit is a major criterion for shoe buyers. Knowledge about sex-related differences in foot shape is important for shoe design. This study supplements the field of knowledge for very small and large feet.
Evidence-based practice recommendations for memory rehabilitation.
2011-03-01

Memory impairment is a common consequence of neurological injury or disease, causing significant disability in everyday life, and is therefore a critical target for rehabilitation intervention. Here we report a review of the available evidence on the efficacy of restitution-oriented therapies and compensatory approaches for memory rehabilitation. A total of 110 studies was systematically classified and analyzed in order to generate evidence-based clinical recommendations for treatment providers. Different key aspects, such as types of brain damage, treatments characteristics and outcome measurements guided the evaluation of the literature as to appraise the potential interaction between patients characteristics, interventions and outcomes. The general conclusion is that memory re-training programs and compensatory approaches are probably effective in ameliorating memory disorders in patients with focal brain lesions, with some evidences of changes in memory functioning extending beyond the trained skills. Externally directed assistive devices and specific learning strategies are effective (with a level D and B of evidence, respectively) in retaining information relevant for daily needs also in patients with degenerative diseases. Some methodological concerns, such as the heterogeneity of subjects, interventions and outcomes studied, may limit the generalization of the present recommendations.
Hominin palaeoecology in Late Pliocene Malawi: First insights from isotopes (<sup>13</sup>C, <sup>18</sup>O) in mammal teeth
2011-03-01

Carbon-13 and oxygen-18 abundances were measured in large mammal skeletal remains (tooth enamel, dentine and bone) from the Chiwondo Beds in Malawi, which were dated by biostratigraphic correlation to ca. 2.5 million years ago. The biologic isotopic patterns, in particular the difference in carbon-13 abundances between grazers and browsers and the difference in oxygen-18 abundances between semi-aquatic and terrestrial herbivores, were preserved in enamel, but not in dentine and bone. The isotopic results obtained from the skeletal remains from the Chiwondo Beds indicate a dominance of savannah habitats with some trees and shrubs. This environment was more arid than the contemporaneous Ndolanya Beds in Tanzania. The present study confirms that robust australopithecines were able to live in relatively arid environments and were not confined to more mesic environments elsewhere in southern Africa.
Fast and accurate resource conflict simulation for performance analysis of multi-core systems
2011-03-01

This work presents a SystemC-based simulation approach for fast performance analysis of parallel software components, using source code annotated with low-level timing properties. In contrast to other source-level approaches for performance analysis, timing attributes obtained from binary code can be annotated even if compiler optimizations are used without requiring changes in the compiler. To consider concurrent accesses to shared resources like caches accurately during a source-level simulation, an extension of the SystemC TLM-2.0 standard for reducing the necessary synchronization overhead is proposed as well. This enables the simulation of low-level timing effects without performing a full-fledged instruction set simulation and at speeds close to pure native execution.
Scalable hybrid verification for embedded software
2011-03-01

The verification of embedded software has become an important subject over the last years. However, neither standalone verification approaches, like simulation-based or formal verification, nor state-of-the-art hybrid/semiformal verification approaches are able to verify large and complex embedded software with hardware dependencies. This work presents a new scalable and extendable hybrid verification approach for the verification of temporal properties in embedded software with hardware dependencies using for the first time a new mixed bottom-up/top-down algorithm. Therefore, new algorithms and methodologies like static parameter assignment and counterexample guided simulation are proposed in order to combine simulation-based and formal verification in a new way. We have successfully applied this hybrid approach to embedded software applications: Motorola's Powerstone Benchmark suite and a complex industrial embedded automotive software. The results show that our approach scales better than stand-alone software model checkers to reach deep state spaces. The whole approach is best suited for fast falsification.
Effective silencing of adhesion molecules on venous endothelial cells for protection of venous bypass grafts
2011-03-01

For the first time, a functional protection of HUEC in a model simulating physiologic vascular conditions by using nonviral transfection of the cells in a setup with high relevance for clinical applicability was demonstrated. Therefore, siRNA transfection of bypass material may develop into a new therapeutic option to improve the quality of venous graft material in the future.
A New Species of Rhinolophus (Chiroptera: Rhinolophidae) from China
2011-03-01

A new species of the genus Rhinolophus is described from Yunnan Province, southwestern China. The new taxon belongs to the Rhinolophus "philippinensis-group" and is distinguished by differences in the nose-leaf structures, craniodental characteristics, and bacular features.
A Common Earth Religion: World Religions from an Ecological Perspective
2011-03-01

On the basis of a critical analysis of the place of world religions in an era of globalization, and drawing on the Gaia hypothesis of James Lovelock, this paper argues for the need for a shift in perspective from a world economy to an earth economy, and for world religions to become earth religions. Here the anthropocentrism of the modern world is overcome and humanity is viewed as an integrated element in planet earth as a whole. This view implies that the world religions need to give back to the earth the virtues they have projected onto the world beyond, and abandon their denial of life and their capacity for violence. In secular terms, this means that world religions need to engage with the ecological perspective and start by applying it to themselves. For if the earth can no longer support life, that means the end of the human world, and the end of world religions.