julilili42/papers huggingface dataset:
S4‐03‐04: The Opposing Roles of Fractalkine Signaling in Alzheimer's Disease Pathogenesis
2010-07-01

The primary neuropathological characteristics of AD include intracellular, filamentous inclusions of hyperphosphorylated microtubule associated protein tau (MAPT) in neurons (neurofibrillary tangles, NFTs) and extracellular deposits of the beta-amyloid peptide in senile plaques. Microglia, the primary immune effector cells in the brain, continually monitor the tissue parenchyma for pathological alterations and become activated in AD. Increasing evidence suggests that microglia contribute to the pathopysiology of AD including; correlational studies in human AD and mouse models, retrospective epidemiological studies demonstrating that use of nonsteroidal anti-inflammatory drugs (NSAIDs) substantially reduces AD risk, and studies utilizing genetically modified mouse models. Neuronal-microglial communication through the chemokine fractalkine (CX3CL1) and its cognate receptor, CX3CR1, plays a critical role in neuroinflammation and neuroprotection. First, CX3CL1 is highly expressed by neurons while CX3CR1 is only expressed by microglia within the CNS. Second, CX3CL1 is neuroprotective in models of neuroinflammation. Finally, studies of Cx3cr1 knockout mice revealed enhanced neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD). To examine the role of CX3CL1-CX3CR1 signaling in Alzheimer's disease, we examined the effects of CX3CR1 deficiency on both beta-amyloid and MAPT pathologies in the APPPS1 (and R1.40) and hTau mouse models of AD, respectively. CX3CR1 deficiency resulted in a gene dose-dependent reduction in beta-amyloid deposition in both the APPPS1 and R1.40 transgenic mouse models of AD that was associated with altered microglial activation, reduced numbers of plaque associated microglia and yet enhanced removal of beta-amyloid. By contrast, CX3CR1 deficiency in the hTau mouse model of MAPT pathology resulted in enhanced microglial activation, phosphorylation and aggregation of MAPT and behavioral impairments. Additional in vitro experiments demonstrate that microglial activation and CX3CR1 deficiency elevates the level of active p38 MAPK and enhances MAPT hyperphosphorylation within neurons that can be blocked by administration of a specific p38 MAPK inhibitor. Our results suggest that CX3CR1 deficiency has opposing effects on the development of the two primary pathologies observed in AD and suggests that “anti-inflammatory” therapies may have opposite effects on AD pathologies at different stages of disease progression.
LONG TERM FOLLOW-UP AND OUTCOME OF LIVER TRANSPLANTATION FROM HCV POSITIVE DONORS: A EUROPEAN MULTICENTRIC CASE-CONTROL STUDY
2010-07-01

BALLARIN, R.1; CUCCHETTI, A.2; SPAGGIARI, M.1; MONTALTI, R.1; DI BENEDETTO, F.1; VALMASONI, M.3; LONGO, C.4; DE RUVO, N.1; CAUTERO, N.1; GUERRINI, G. P.1; NADALIN, S.5; TROISI, R.6; CILLO, U.3; PINNA, A. D.2; BURRA, P.7; GERUNDA, G. E.1 Author Information
IS ZOOM-ENDOSCOPIC SUBAQUAL MUCOSA EVALUATION ABLE TO REPLACE BIOPSY IN THE DIAGNOSTICS OF ACUTE TISSUE REJECTION IN PATIENTS WITH SMALL INTESTINE TRANSPLANTATION?
2010-07-01

Kratt, T.1; Minkley, L.2; Stueker, D.2; Steurer, W.3; Ladurner, R.2; Küper, M.2; Thiel, C.2; Lamprecht, H. G.4; Fend, F.5; von Weyhern, Hann C.5; Schröppel, K.6; Königsrainer, A.1; Nadalin, S.1 Author Information
Pruning population size in XCS for complex problems
2010-07-01

In this paper, we show how to prune the population size of the Learning Classifier System XCS for complex problems. We say a problem is complex, when the number of specified bits of the optimal start classifiers (the problem dimension) is not constant. First, we derive how to estimate an equivalent problem dimension for complex problems based on the optimal start classifiers. With the equivalent problem dimension, we calculate the optimal maximum population size just like for regular problems, which has already been done. We empirically validate our results. Furthermore, we introduce a subsumption method to reduce the number of classifiers. In contrast to existing methods, we subsume the classifiers after the learning process, so subsuming does not hinder the evolution of optimal classifiers, which has been reported previously. After subsumption, the number of classifiers drops to about the order of magnitude of the optimal classifiers while the correctness rate nearly stays constant.
ChemInform Abstract: Rare Earth Carbodiimide Silicates: RE2(CN2)(SiO4).
2010-07-01

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Structure−Activity Study of Dihydrocinnamic Acids and Discovery of the Potent FFA1 (GPR40) Agonist TUG-469
2010-07-02

The free fatty acid 1 receptor (FFA1 or GPR40), which is highly expressed on pancreatic β-cells and amplifies glucose-stimulated insulin secretion, has emerged as an attractive target for the treatment of type 2 diabetes. Several FFA1 agonists containing the para-substituted dihydrocinnamic acid moiety are known. We here present a structure-activity relationship study of this compound family suggesting that the central methyleneoxy linker is preferable for the smaller compounds, whereas the central methyleneamine linker gives higher potency to the larger compounds. The study resulted in the discovery of the potent and selective full FFA1 agonist TUG-469 (29).
Differential Effects of Chromosome 9p21 Variation on Subphenotypes of Intracranial Aneurysm
2010-07-02

Background and Purpose— Recently, a genome-wide association study identified associations between single nucleotide polymorphisms on chromosome 9p21 and risk of harboring intracranial aneurysm (IA). Aneurysm characteristics or subphenotypes of IAs, such as history of subarachnoid hemorrhage, presence of multiple IAs and location of IAs, are clinically important. We investigated whether the association between 9p21 variation and risk of IA varied among these subphenotypes. Methods— We conducted a case-control study of 981 cases and 699 controls in Japanese. Four single nucleotide polymorphisms tagging the 9p21 risk locus were genotyped. The OR and 95% CI were estimated using logistic regression analyses. Results— Among the 4 single nucleotide polymorphisms, rs1333040 showed the strongest evidence of association with IA ( P =1.5×10 −6 ; per allele OR, 1.43; 95% CI, 1.24–1.66). None of the patient characteristics (gender, age, smoking, and hypertension) was a significant confounder or effect modifier of the association. Subgroup analyses of IA subphenotypes showed that among the most common sites of IAs, the association was strongest for IAs of the posterior communicating artery (OR, 1.69; 95% CI, 1.26–2.26) and not significant for IAs in the anterior communicating artery (OR, 1.22; 95% CI, 0.96–1.57). When dichotomizing IA sites, the association was stronger for IAs of the posterior circulation–posterior communicating artery group (OR, 1.73; 95% CI, 1.32–2.26) vs the anterior circulation group (OR, 1.28; 95% CI, 1.07–1.53). Heterogeneity in these ORs was significant ( P =0.032). The associations did not vary when stratifying by history of subarachnoid hemorrhage (OR, 1.42; 95% CI, 1.18–1.71 for ruptured IA; OR, 1.27; 95% CI, 1.00–1.62 for unruptured IA) or by multiplicity of IA (OR, 1.57; 95% CI, 1.21–2.03 for multiple IAs; OR, 1.36; 95% CI, 1.15–1.61 for single IA). Conclusions— Our results suggest that genetic influence on formation may vary between IA subphenotypes.
To carry or not to carry — Is this the question? Disentangling the carry effect in multi-digit addition
2010-07-03

Recent research has suggested addition performance to be determined by both the need for a carry operation and problem size. Nevertheless, it has remained debatable, how these two factors are interrelated. In the current study, this question was pursued by orthogonally manipulating carry and problem size in two-digit addition verification. As the two factors interacted reliably, our results indicate that the carry effect is moderated by number magnitude processing rather than representing a purely procedural, asemantic sequence of processing steps. Moreover, it was found that the carry effect may not be a purely categorical effect but may be driven by continuous characteristics of the sum of the unit digits as well. Since the correct result of a carry problem can only be derived by integrating and updating the magnitudes of tens and units within the place-value structure of the Arabic number system, the present study provides evidence for the idea that decomposed processing of tens and units also transfers to mental arithmetic.
The Pedicled Serratus Anterior Muscle Wrap-around Flap
2010-07-03

A new field of application of the pedicled serratus anterior muscle flap is presented. Severe axillary neuropathic pain and distress due to neuroma formation were treated by wrapping the pedicled serratus anterior muscle flap around the brachial plexus. Covering the fascicles by well vascularized muscle tissue results in significant postoperative pain relief. We describe a new method in the treatment of severe neuropathic pain syndromes originating from the brachial plexus, with good result.
The face of Noonan syndrome: Does phenotype predict genotype
2010-07-06

Abstract The facial photographs of 81 individuals with Noonan syndrome, from infancy to adulthood, have been evaluated by two dysmorphologists (JA and MZ), each of whom has considerable experience with disorders of the Ras/MAPK pathway. Thirty‐two of this cohort have PTPN11 mutations, 21 SOS1 mutations, 11 RAF1 mutations, and 17 KRAS mutations. The facial appearance of each person was judged to be typical of Noonan syndrome or atypical. In each gene category both typical and unusual faces were found. We determined that some individuals with mutations in the most commonly affected gene, PTPN11 , which is correlated with the cardinal physical features, may have a quite atypical face. Conversely, some individuals with KRAS mutations, which may be associated with a less characteristic intellectual phenotype and a resemblance to Costello and cardio‐facio‐cutaneous syndromes, can have a very typical face. Thus, the facial phenotype, alone, is insufficient to predict the genotype, but certain facial features may facilitate an educated guess in some cases. © 2010 Wiley‐Liss, Inc.
The eastward displacement of a freely falling body on the rotating Earth: Newton and Hooke's debate of 1679
2010-07-06

Abstract In this article I would like to tell the story of the beginning of modern theoretical physics, freed from all kinds of questionable anecdotes which have entered the scientific literature over the centuries. It all began in the seventeenth century when the mathematical theory of astronomy began to take shape. A major step in the history of modern science was taken when a few members of The Royal Society in London realized that the laws ruling the motions of heavenly bodies as manifested in Kepler's three laws are also effective in the dynamics of Earth‐bound particle motion. Everything started, not with I. Newton, but with R. Hooke. Not Newton's falling apple (Voltaire's invention), but a far‐reaching response by R. Hooke to a letter by I. Newton, dated November 28, 1679, ignited Newton's interest in gravity. That letter contained the famous spiral which a falling body would follow when released from a certain height above the surface of the Earth. Hooke's answer, based on Keplerian orbits, expressed the opinion that the body's trajectory would rather follow an elliptical path. In his spiral sketch Newton, however, predicted correctly that the falling body would be found to suffer an eastward deviation from the vertical in consequence of the Earth's rotation. In the course of time, many a researcher, including Hooke himself, was able to verify this conjecture. But it took until 1803 for the first satisfactory calculation of the eastward displacement of a freely falling body to be performed, and was provided by C.F. Gauss.
A putative TRAPPII tethering factor is required for cell plate assembly during cytokinesis in Arabidopsis
2010-07-06

*At the end of the cell cycle, the plant cell wall is deposited within a membrane compartment referred to as the cell plate. Little is known about the biogenesis of this transient membrane compartment. *We have positionally cloned and characterized a novel Arabidopsis gene, CLUB, identified by mutation. *CLUB/AtTRS130 encodes a putative TRAPPII tethering factor. club mutants are seedling-lethal and have a canonical cytokinesis-defective phenotype, characterized by the appearance of bi- or multinucleate cells with cell wall stubs, gaps and floating walls. Confocal microscopy showed that in club mutants, KNOLLE-positive vesicles formed and accumulated at the cell equator throughout cytokinesis, but failed to assemble into a cell plate. Similarly, electron micrographs showed large vesicles loosely connected as patchy, incomplete cell plates in club root tips. Neither the formation of KNOLLE-positive vesicles nor the delivery of these vesicles to the cell equator appeared to be perturbed in club mutants. Thus, the primary defect in club mutants appears to be an impairment in cell plate assembly. *As a putative tethering factor required for cell plate biogenesis, CLUB/AtTRS130 helps to define the identity of this membrane compartment and comprises an important handle on the regulation of cell plate assembly.
A53T-Alpha-Synuclein Overexpression Impairs Dopamine Signaling and Striatal Synaptic Plasticity in Old Mice
2010-07-07

Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches.
Who integrates the networks of knowledge in Wikipedia?
2010-07-07

In the study presented in this article we investigated two related knowledge domains, physiology and pharmacology, from the German version of Wikipedia. Applying the theory of knowledge building to this community, we studied the authors of integrative knowledge.
Role of acidic sphingomyelinase in thymol‐mediated dendritic cell death
2010-07-07

Abstract Scope : Thymol is a component of several plants with antimicrobial activity. Little is known about the effects of thymol on immune cells of the host. This study addressed the effects of thymol on dendritic cells (DCs), regulators of innate and adaptive immunity. Methods and results : Immunohistochemistry, Western blotting and fluorescence‐activated cell sorting analysis were performed in bone marrow‐derived DCs either from wild‐type mice or from mice lacking acid sphingomyelinase (ASM −/− ) treated and untreated for 24 h with thymol (2–100 μg/mL). Thymol treatment resulted in activation of ASM, stimulation of ceramide formation, downregulation of anti‐apoptotic Bcl‐2 and Bcl‐xL proteins, activation of caspase 3 and caspase 8, DNA fragmentation as well as cell membrane scrambling. The effects were dependent on the presence of ASM and were lacking in ASM −/− mice or in wild‐type DCs treated with sphingomyelinase inhibitor amitriptyline. Conclusion : Thymol triggers suicidal DC death, an effect mediated by and requiring activation of ASM.
The Sense and Non-Sense of Holdout Sample Validation in the Presence of Endogeneity
2010-07-07

Market response models that use field-generated data are required to address potential endogeneity in the regressors to obtain consistent parameter estimates. Another requirement is that market response models predict well in a holdout sample. Combining both requirements, it may seem reasonable to subject an endogeneity-corrected model to a holdout prediction task, and this is quite common in the academic marketing literature. One may be inclined to expect that the consistent parameter estimates obtained via instrumental variable (IV) estimation predict better than the biased ordinary least squares (OLS) estimates. This paper shows that this expectation is incorrect. That is, if the holdout sample is similar to the estimation sample so that the regressors are endogenous in both samples, holdout sample validation favors regression estimates that are not corrected for endogeneity (i.e., OLS) over estimates that are corrected for endogeneity (i.e., IV estimation). A key take-away is that if consistent parameter estimates are the primary model objective, the model should be validated with an exogenous (rather than endogenous) holdout sample. If prediction is the primary model objective, we recommend refraining from correcting for endogeneity with IV estimation.
Pallidal and thalamic deep brain stimulation in myoclonus‐dystonia
2010-07-08

Abstract Deep brain stimulation (DBS) of the internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (VIM) are established treatment options in primary dystonia and tremor syndromes and have been reported anecdotally to be efficacious in myoclonus‐dystonia (MD). We investigated short‐ and long‐term effects on motor function, cognition, affective state, and quality of life (QoL) of GPi‐ and VIM‐DBS in MD. Ten MD‐patients (nine ε‐sarcoglycan‐mutation‐positive) were evaluated pre‐ and post‐surgically following continuous bilateral GPi‐ and VIM‐DBS at four time points: presurgical, 6, 12, and as a last follow‐up at a mean of 62.3 months postsurgically, and in OFF‐, GPi‐, VIM‐, and GPi‐VIM‐DBS conditions by validated motor [unified myoclonus rating scale (UMRS), TSUI Score, Burke‐Fahn‐Marsden dystonia rating scale (BFMDRS)], cognitive, affective, and QoL‐scores. MD‐symptoms significantly improved at 6 months post‐surgery (UMRS: 61.5%, TSUI Score: 36.5%, BFMDRS: 47.3%). Beneficial effects were sustained at long‐term evaluation post‐surgery (UMRS: 65.5%, TSUI Score: 35.1%, BFMDRS: 48.2%). QoL was significantly ameliorated; affective status and cognition remained unchanged postsurgically irrespective of the stimulation conditions. No serious long‐lasting stimulation‐related adverse events (AEs) were observed. Both GPi‐ and VIM‐DBS offer equally effective and safe treatment options for MD. With respect to fewer adverse, stimulation‐induced events of GPi‐DBS in comparison with VIM‐DBS, GPi‐DBS seems to be preferable. Combined GPi‐VIM‐DBS can be useful in cases of incapaciting myoclonus, refractory to GPi‐DBS alone. © 2010 Movement Disorder Society
Brain Stimulation: New Vistas for the Exploration and Treatment of Tinnitus
2010-07-08

SUMMARY Aims : Tinnitus, the perception of sounds or noise in the absence of auditory stimuli, is a frequent and often severely disabling symptom of different disorders of the auditory system. Attempts to develop evidence‐based therapies have been thwarted by a poor understanding of the underlying pathophysiology. However, recent work points toward a pivotal role of maladaptive cortical reorganization in the generation and perpetuation of tinnitus. Changes in the representation of sounds, abnormalities of oscillatory activity, and hyperactivity in higher order areas of auditory processing have been linked with the perception of tinnitus. Brain stimulation techniques have entered the field and have opened exciting new perspectives for the modulation of dysfunctional brain activity. In this review, a comprehensive overview on the use of brain‐stimulation techniques in the exploration and experimental treatment of tinnitus is provided. Discussions : Noninvasive and invasive brain stimulation techniques, for example, transcranial magnetic stimulation (TMS), direct current stimulation (tDCS), and direct electrical cortical stimulation gave rise to a new line of investigation in tinnitus research. First, it has been shown that focal interference with presumably pathological cortical function can reduce tinnitus at least transiently. Second, the reduction of tinnitus‐associated enhancement of cortical activity by neuronavigated TMS has been demonstrated to ameliorate tinnitus. Third, preliminary data suggest that repeated application of TMS or continuous cortical stimulation may lead to a longer lasting suppression of tinnitus. Conclusions : These proof of principle studies point toward a new option for the investigation and neurophysiology based treatment of tinnitus. Based on these findings, larger scale randomized clinical trials are needed to explore the efficacy of different brain stimulation techniques and parameters as well as the optimal target sites and treatment schedules. Particularly, a careful evaluation of clinical relevance under consideration of an adequate sham control and attention to possible unwanted side effects of these new interventions are indispensable.
Interacting trapped bosons yield fragmented condensate states in low dimensions
2010-07-09

We investigate the level population statistics and degree of coherence encoded in the single-particle density matrix of harmonically trapped low-dimensional [quasi-one-dimensional (quasi-1D) or quasi-two-dimensional (quasi-2D)] Bose gases with repulsive contact interactions. Using a variational analysis, we derive fragmentation of the condensate in the weakly confining directions into two (quasi-1D) respectively three (quasi-2D) mutually incoherent macroscopic pieces, upon increasing a dimensionless interaction measure beyond a critical value. Fragmented condensate many-body states in low-dimensional systems therefore occur well before the thermodynamic limit of infinite extension is reached, in which phase fluctuations of the matter wave field create an infinite number of nonmacroscopic fragments.
Medium Chain Acylcarnitines Dominate the Metabolite Pattern in Humans under Moderate Intensity Exercise and Support Lipid Oxidation
2010-07-12

Medium chain acylcarnitines were identified and characterized by a functional metabolomics approach as the dominating biomarkers during a moderately intense exercise bout possessing the power to support fat oxidation. This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.
Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation
2010-07-13

Abstract Cytomegalovirus (CMV) disease and infection refractory to antiviral treatment after allogeneic stem cell transplantation (allo-SCT) is associated with a high mortality. Adoptive transfer of CMV-specific T cells could reconstitute viral im-munity after SCT and could protect from CMV-related complications. However, logistics of producing virus-specific T-cell grafts limited the clinical application. We treated 18 patients after allo-SCT from human leukocyte antigen–mismatched/haploidentical or human leukocyte antigen–matched unrelated donors with polyclonal CMV-specific T cells generated by ex vivo stimulation with pp65, followed by isolation of interferon-γ–producing cells. Patients with CMV disease or viremia refractory to antiviral chemotherapy or both were eligible for adoptive T-cell transfer and received a mean of 21 × 103/kg pp65-specific T cells. In 83% of cases CMV infection was cleared or viral burden was significantly reduced, even in cases of CMV encephalitis (n = 2). Viral control was associated with in vivo expansion of CMV-specific T lymphocytes in 12 of 16 evaluable cases, resulting in reconstitution of antiviral T-cell responses, without graft-versus-host disease induction or acute side effects. Our findings indicate that the infusion of low numbers of CMV-specific T cells is safe, feasible, and effective as a treatment on demand for refractory CMV infection and CMV disease after allo-SCT.