julilili42/papers huggingface dataset:
Pathogenic protein seeding in alzheimer disease and other neurodegenerative disorders
2011-09-01

Abstract The misfolding and aggregation of specific proteins is a seminal occurrence in a remarkable variety of neurodegenerative disorders. In Alzheimer disease (the most prevalent cerebral proteopathy), the two principal aggregating proteins are β‐amyloid (Aβ) and tau. The abnormal assemblies formed by conformational variants of these proteins range in size from small oligomers to the characteristic lesions that are visible by optical microscopy, such as senile plaques and neurofibrillary tangles. Pathologic similarities with prion disease suggest that the formation and spread of these proteinaceous lesions might involve a common molecular mechanism—corruptive protein templating. Experimentally, cerebral β‐amyloidosis can be exogenously induced by exposure to dilute brain extracts containing aggregated Aβ seeds. The amyloid‐inducing agent probably is Aβ itself, in a conformation generated most effectively in the living brain. Once initiated, Aβ lesions proliferate within and among brain regions. The induction process is governed by the structural and biochemical nature of the Aβ seed, as well as the attributes of the host, reminiscent of pathogenically variant prion strains. The concept of prionlike induction and spreading of pathogenic proteins recently has been expanded to include aggregates of tau, α‐synuclein, huntingtin, superoxide dismutase‐1, and TDP‐43, which characterize such human neurodegenerative disorders as frontotemporal lobar degeneration, Parkinson/Lewy body disease, Huntington disease, and amyotrophic lateral sclerosis. Our recent finding that the most effective Aβ seeds are small and soluble intensifies the search in bodily fluids for misfolded protein seeds that are upstream in the proteopathic cascade, and thus could serve as predictive diagnostics and the targets of early, mechanism‐based interventions. Establishing the clinical implications of corruptive protein templating will require further mechanistic and epidemiologic investigations. However, the theory that many chronic neurodegenerative diseases can originate and progress via the seeded corruption of misfolded proteins has the potential to unify experimental and translational approaches to these increasingly prevalent disorders. Ann Neurol 2011;70:532–540
Multivesicular Bodies Mature from the Trans-Golgi Network/Early Endosome in Arabidopsis
2011-09-01

Abstract The plant trans-Golgi network/early endosome (TGN/EE) is a major hub for secretory and endocytic trafficking with complex molecular mechanisms controlling sorting and transport of cargo. Vacuolar transport from the TGN/EE to multivesicular bodies/late endosomes (MVBs/LEs) is assumed to occur via clathrin-coated vesicles, although direct proof for their participation is missing. Here, we present evidence that post-TGN transport toward lytic vacuoles occurs independently of clathrin and that MVBs/LEs are derived from the TGN/EE through maturation. We show that the V-ATPase inhibitor concanamycin A significantly reduces the number of MVBs and causes TGN and MVB markers to colocalize in Arabidopsis thaliana roots. Ultrastructural analysis reveals the formation of MVBs from the TGN/EE and their fusion with the vacuole. The localization of the ESCRT components VPS28, VPS22, and VPS2 at the TGN/EE and MVBs/LEs indicates that the formation of intraluminal vesicles starts already at the TGN/EE. Accordingly, a dominant-negative mutant of VPS2 causes TGN and MVB markers to colocalize and blocks vacuolar transport. RNA interference–mediated knockdown of the annexin ANNAT3 also yields the same phenotype. Together, these data indicate that MVBs originate from the TGN/EE in a process that requires the action of ESCRT for the formation of intraluminal vesicles and annexins for the final step of releasing MVBs as a transport carrier to the vacuole.
Chronic Stroke Survivors Benefit From High-Intensity Aerobic Treadmill Exercise
2011-09-01

Background and objective. Ambulatory subjects after stroke may benefit from gait-oriented cardiovascular fitness training, but trials to date have not primarily assessed older persons. Methods. Thirty-eight subjects (age &gt;60 years) with residual hemiparetic gait were enrolled &gt;6 months after stroke. Participants were randomized to receive 3 months (3×/week) progressive graded, high-intensity aerobic treadmill exercise (TAEX) or conventional care physiotherapy. Primary outcome measures were peak exercise capacity (Vo 2peak ) and sustained walking capacity in 6-minute walks (6MW). Secondary measures were gait velocity in 10-m walks, Berg Balance Scale, functional leg strength (5 chair-rise), self-rated mobility (Rivermead Mobility Index), and quality of life (SF-12). Results. Thirty-six participants completed the study (18 TAEX, 18 controls). TAEX but not conventional care improved Vo 2peak (difference 6.4 mL/kg/min, P &lt; .001) and 6MW (53 m, P &lt; .001). Likewise, maximum walking speed (0.13 m/s, P = .01), balance ( P &lt; .05), and the mental subscore of the SF-12 ( P &lt; .01) improved more after TAEX. Gains in Vo 2peak correlated with the degree at which training intensity could be progressed in the individual participant ( P &lt; .01). Better walking was related to progression in treadmill velocity and training duration ( P &lt; .001). Vo 2peak and 6MW performances were still higher 1 year after the end of training when compared with the baseline, although endurance walking (6MW) at 1 year was lower than immediately after training ( P &lt; .01). Conclusion. This trial demonstrates that TAEX effectively improves cardiovascular fitness and gait in persons with chronic stroke.
Making environmental sensors on plastic foil
2011-09-01

The driving forces for organic and printed electronics are the display and lightning, solar cell, battery and electronics (e.g., RFID) industries1. The complete technology chain is being established in the fields of materials preparation, processing and characterization equipment, and production. Over the last decade, there has been a significant increase in the efforts dedicated to the development and implementation of electronic components on flexible and stretchable substrates for other types of application, such assensing, and notable results have been obtained by different research groups2-8. This technology could result in sensors being introduced to new settings, by significantly reducing their production cost and by adding new functionalities.
Dengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells
2011-09-01

Dengue virus (DENV) is a member of the Flaviviridae and a globally (re)emerging pathogen that causes serious human disease. There is no specific antiviral or vaccine for dengue virus infection. Flavivirus capsid (C) is a structural protein responsible for gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. Flaviviral replication is known to occur in the cytoplasm yet a large portion of capsid protein localizes to the nucleus during infection. The reasons for the nuclear presences of capsid are not completely understood. Here, we expressed mature DENV C in a tandem affinity purification assay to identify potential binding partners in human liver cells. DENV C targeted the four core histones, H2A, H2B, H3 and H4. DENV C bound recombinant histones in solution and colocalized with histones in the nucleus and cytoplasm of liver cells during DENV infection. We show that DENV C acts as a histone mimic, forming heterodimers with core histones, binding DNA and disrupting nucleosome formation. We also demonstrate that DENV infection increases the amounts of core histones in livers cells, which may be a cellular response to C binding away the histone proteins. Infection with DENV additionally alters levels of H2A phosphorylation in a time-dependent manner. The interactions of C and histones add an interesting new role for the presence of C in the nucleus during DENV infection.
Impairment of Immunoproteasome Function by β5i/LMP7 Subunit Deficiency Results in Severe Enterovirus Myocarditis
2011-09-01

Proteasomes recognize and degrade poly-ubiquitinylated proteins. In infectious disease, cells activated by interferons (IFNs) express three unique catalytic subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 forming an alternative proteasome isoform, the immunoproteasome (IP). The in vivo function of IPs in pathogen-induced inflammation is still a matter of controversy. IPs were mainly associated with MHC class I antigen processing. However, recent findings pointed to a more general function of IPs in response to cytokine stress. Here, we report on the role of IPs in acute coxsackievirus B3 (CVB3) myocarditis reflecting one of the most common viral disease entities among young people. Despite identical viral load in both control and IP-deficient mice, IP-deficiency was associated with severe acute heart muscle injury reflected by large foci of inflammatory lesions and severe myocardial tissue damage. Exacerbation of acute heart muscle injury in this host was ascribed to disequilibrium in protein homeostasis in viral heart disease as indicated by the detection of increased proteotoxic stress in cytokine-challenged cardiomyocytes and inflammatory cells from IP-deficient mice. In fact, due to IP-dependent removal of poly-ubiquitinylated protein aggregates in the injured myocardium IPs protected CVB3-challenged mice from oxidant-protein damage. Impaired NFκB activation in IP-deficient cardiomyocytes and inflammatory cells and proteotoxic stress in combination with severe inflammation in CVB3-challenged hearts from IP-deficient mice potentiated apoptotic cell death in this host, thus exacerbating acute tissue damage. Adoptive T cell transfer studies in IP-deficient mice are in agreement with data pointing towards an effective CD8 T cell immune. This study therefore demonstrates that IP formation primarily protects the target organ of CVB3 infection from excessive inflammatory tissue damage in a virus-induced proinflammatory cytokine milieu.
Epstein-Barr Virus-positive Diffuse Large B-cell Lymphomas of the Elderly
2011-09-01

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly has been included in the 2008 WHO classification as a new provisional entity and is defined as blastic, clonal B-cell proliferation associated with EBV occurring in patients over 50 years of age, presumably due to senescence of the immune system. Secondary immunodeficiencies must be excluded. Morphologically, the predominant polymorphic subtype shows a mixed proliferation of large transformed cells, plasma cells, plasmablasts, lymphocytes, and commonly Reed-Sternberg (RS)-like cells, whereas the monomorphic subtype reveals sheets of large cells. An additional characteristic feature is large areas of "geographical" necrosis. EBV+ DLBCL of the elderly is positive for pan-B cell markers and often for CD30. EBV infection detected by Epstein Barr early RNA in situ hybridization should be present in the majority of tumor cells. Most cases express LMP1 and up to 32% EBNA2, the latter a sign of an impaired immune system. The most challenging differential diagnosis is EBV+ classical Hodgkin lymphoma in older patients. Strong, homogeneous expression of B-cell markers, including transcription factors OCT2 and BOB.1, and lack of CD15 support a diagnosis of EBV+ DLBCL. EBV+ DLBCL of the elderly accounts for 8% to 10% of DLBCL in Asian countries, but seems to be uncommon in Western populations, indicating an ethnic or geographic predisposition. Clinically, patients may present with nodal or extranodal involvement. B-symptoms and poor performance status are common, and prognosis is significantly inferior compared with EBV- cases. Whether EBV+DLBCL of the elderly represents a true entity or only a DLBCL variant remains to be determined.
Influence of foot positions on the spine and pelvis
2011-09-01

Abstract Objective The management of knee osteoarthritis includes the use of wedged shoe insoles to unload the affected knee compartment. Although the biomechanical effects of shoe insoles on the knee joint are known and described, only little is known about their influence on the pelvis and spine. Therefore, the purpose of this study was to evaluate the effects of different foot positions, such as how they could be achieved by shoe insoles, on pelvic position and spinal posture. Methods A total of 51 test subjects were measured for this study. The different foot positions (inner and outer margin increase, positive and negative heel height) were simulated with a specially designed stand platform. A rasterstereographic device was used to measure the immediate effects of the simulated foot positions on the pelvic position and spinal posture. Results Positive and negative heel heights as well as an increase of the outer margin of the platform led to significant changes of the pelvic tilt. The pelvic torsion also changed significantly during positive heel height changes of 10 and 15 mm and increases of the outer margin of the foot. No significant changes were found between foot position and spinal parameters. Conclusion The results of our study support the existence of a kinematic chain, where changes of foot position also led to significant alterations of the pelvic position. Whether these changes could lead to long‐term pathologic alterations still needs to be evaluated. However, in our setting, no correlation between foot position and spinal posture changes was found.
Recharge estimation using remotely sensed evapotranspiration in an irrigated catchment in southeast Australia
2011-09-01

Abstract Reliable estimates of groundwater recharge are required for the sustainable management of surface and ground water resources in semi‐arid regions particularly in irrigated regions. In this study, groundwater recharge was estimated for an irrigated catchment in southeast Australia using a semi‐distributed hydrological model (SWAT). The model was calibrated under the dry climatic conditions for the period from August 2002 to July 2003 using flow and remotely sensed evapotranspiration (ET). The model was able to simulate observed monthly drain flow and spatially distributed remotely sensed ET. Recharge tended to be higher for irrigated land covers, such as perennial pasture, than for non‐irrigated land. On average, the estimated annual catchment recharge ranged between 147 and 289 mm which represented about 40% of the total rainfall and irrigation inputs. The optimized soil parameters indirectly reflected flow bypassing the soil matrix that could be responsible for this substantial amount of recharge. Overall, the estimated recharge was much more than that previously estimated for the wetter years. Copyright © 2011 John Wiley &amp; Sons, Ltd.
Large deletions of theKCNV2gene are common in patients with cone dystrophy with supernormal rod response
2011-09-01

Cone dystrophy with supernormal rod response (CDSRR) is considered to be a very rare autosomal recessive retinal disorder. CDSRR is associated with mutations in KCNV2, a gene that encodes a modulatory subunit (Kv8.2) of a voltage-gated potassium channel. In this study, we found that KCNV2 mutations are present in a substantial fraction (2.2-4.3%) of a sample of 367 independent patients with a variety of initial clinical diagnoses of cone malfunction, indicating that CDSRR is underdiagnosed and more common than previously thought. In total, we identified 20 different KCNV2 mutations; 15 of them are novel. A new finding of this study is the substantial proportion of large deletions at the KCNV2 locus that accounts for 15.5% of the mutant alleles in our sample. We determined the breakpoints and size of all five different deletions, which ranged between 10.9 and 236.8 kb. Two deletions encompass the entire KCNV2 gene and one also includes the adjacent VLDLR gene. Furthermore, we investigated N-terminal amino acid substitution mutations for its effect on interaction with Kv2.1 using yeast two-hybrid technology. We found that these mutations dramatically reduce or abolish this interaction suggesting a lack of assembly of heteromeric Kv channels as one underlying pathomechanism of CDSRR.
Online counseling via e-mail for breast cancer patients on the German internet: preliminary results of a psychoeducational intervention
2011-09-01

Objectives: The internet offers new possibilities in psychosocial patient care. However, empirical data are lacking for oncological patients. A field-experimental study was conducted to obtain initial data to enable evaluation of the effectiveness of online counseling via e-mail for breast cancer patients. A secondary objective was to explore how patients reached by the service can be characterized on psychosocial status and illness. Methods: On a dedicated German-language website, 235 breast cancer patients registered for psychosocial counseling via e-mail. 133 registrants were randomly assigned to a treatment group to receive immediate counseling or to a waiting list control group. The two-month counseling session took the form of a psychoeducation, individually tailored to each patient. Psychosocial outcome measures including psychological distress (BSI) and quality of life (EORTC QLQ-C30) were assessed at registration and at a two-month follow-up. Descriptive data were recorded at registration. At the conclusion of the program, participants were asked to complete a patient satisfaction questionnaire (ZUF-8). Results: BSI responses showed that 85% of all patients were initially diagnosable with comorbid psychopathology. Despite high severity of distress and attendant large reductions in quality of life, 72% of all patients were not obtaining conventional assistance. Among counseling participants (n=31), no significant improvements in distress or quality of life were found in comparison to the control group (n=34), but patient satisfaction was nonetheless high. Conclusion: The study demonstrates that online counseling via e-mail reaches patients with unmet therapeutic needs, but also indicated its limitations, suggesting that the online setting may be most useful for prompting and supporting a transition to conventional counseling services.
Modeling the eardrum as a string with distributed force
2011-09-01

In this paper, an analytical model of the tympanic membrane is introduced where the two-dimensional tympanic membrane is reduced to a one-dimensional string. It is intended to bridge the gap between lumped-element models and finite-element models. In contrast to known lumped-element models, the model takes the distributed effect of the sound field on the tympanic membrane into account. Compared to finite-element models, it retains the advantage of a low number of parameters. The model is adjusted to forward and reverse transfer functions of the guinea-pig middle ear. Although the fitting to experimental data is not perfect, important conclusions can be drawn. For instance, the model shows that the delay of surface waves on the tympanic membrane can be different from the signal transmission delay of the tympanic membrane. In a similar vein, the standing wave ratio on the tympanic membrane and within the ear canal can considerably differ. Further, the model shows that even in a low-loss tympanic membrane the effective area, which commonly is associated with the transformer ratio in a lumped-element and some hybrid circuit models, not only is frequency-dependent, but also different for forward and reverse transduction.
Petrography and whole-rock geochemical characteristics of Västervik granitoids to syenitoids, southeast Sweden: constraints on petrogenesis and tectonic setting at the southern margin of the Svecofennian domain
2011-09-01

Granitoid to syenitoid petrogenesis along the Laurentia–Baltica continental margin occurred in two cycles. Within the Fennoscandian Shield, the first cycle is correlated with the 1.95–1.8 Ga Svecofennian domain and the second is correlated with the 1.85–1.65 Ga Transscandinavian Igneous Belt (TIB). Affiliation of Palaeoproterozoic granitoids to syenitoids (∼1.8 Ga) in a transitional zone between the Svecofennian domain to the north and the TIB to the south in the Västervik area in southeast Sweden, is highly debated. In this study, the Västervik granitoids to syenitoids have been studied for major and trace element, whole-rock Sm–Nd and U–Pb single zircon isotopic compositions. Field observations, petrography and geochemical composition allow discrimination into five groups ranging from tonalitic to syenogranitic compositions. Geochemical signatures indicate magnesian, metaluminous cordilleran character for three of them, whereas the two most differentiated groups show a transition into ferroan, peraluminous granites with postorogenic or A-type characters. The former three groups may be correlated with the TIB-1 suite at 1.81–1.77 Ga. The older of the A-type groups may be correlated with the TIB-0 suite that intruded at 1.87–1.84 Ga whereas the younger group possibly is related to the so-called granite–pegmatite suite. An earlier tectonic model implies a migration of the subduction zone system to the present southwest. The defined granitoid to syenitoid groups of the Västervik region fit nicely into the model and support the idea of a new tectonic cycle to the south of the Bergslagen region.
Training Device for Dental Students to Practice Mirror‐Inverted Movements
2011-09-01

The goal of this study was to explore whether the ability of precise mirror‐inverted movements can be learned and improved with the device Mirroprep and whether practice success can be transferred to the clinical situation. Three groups of students at different levels of dental study and different achievement levels were asked to perform a drawing exercise with indirect vision using Mirroprep. Further, the group of most senior students were asked whether the motor skills learned with this device were helpful in clinical tooth preparations by use of the dental mirror. According to the test results, we were able to show that mirror‐inverted motor functions can be learned and improved by practice and that it is also helpful for performing tooth preparations. Because of this, it is deemed reasonable for students to start practicing with the training device during their preclinical studies and to have their skills tested.
Efficient self-adjusting, similarity-based location fingerprinting with passive UHF RFID
2011-09-01

In this paper we present extensive experimental results of location fingerprinting with passive UHF radio-frequency identification (RFID). As recent passive RFID hardware provides information about received signal strength (RSS), we evaluate its usefulness in the context of fingerprinting based on classical vector similarity measures. We analyze the impact of decisive parameters of the applied approach and also select them automatically via cross-validation, including the most appropriate similarity measure. A further novelty is an RSS thresholding mechanism which reduces the computational demands of comparing fingerprints. This technique is especially useful in surroundings which are densely equipped with RFID tags, such as future supermarkets or logistic centers. We conducted real-world experiments with a mobile robot and two different RFID readers. Results are reported both for global localization in each time frame and for time-filtered position tracking. We provide the experimental data of this work for download.