Miracle-dz/UniFAR-FTUs huggingface dataset:
Unraveling Mechanisms Underlying Partial Agonism in 5-HT3A Receptors

Partial agonists have emerged as attractive therapeutic molecules. 2-Me-5HT and tryptamine have been defined as partial agonists of 5-HT3 receptors on the basis of macroscopic measurements. Because several mechanisms may limit maximal responses, we took advantage of the high-conductance form of the mouse serotonin type 3A (5-HT3A) receptor to understand their molecular actions. Individual 5-HT-bound receptors activate in long episodes of high open probability, consisting of groups of openings in quick succession. The activation pattern is similar for 2-Me-5HT only at very low concentrations since profound channel blockade takes place within the activating concentration range. In contrast, activation episodes are significantly briefer in the presence of tryptamine. Generation of a full activation scheme reveals that the fully occupied receptor overcomes transitions to closed preopen states (primed states) before opening. Reduced priming explains the partial agonism of tryptamine. In contrast, 2-Me-5HT is not a genuine partial agonist since priming is not dramatically affected and its low apparent efficacy is mainly due to channel blockade. The analysis also shows that the first priming step is the rate-limiting step and partial agonists require an increased number of priming steps for activation. Molecular docking suggests that interactions are similar for 5-HT and 2-Me-5HT but slightly different for tryptamine. Our study contributes to understanding 5-HT3A receptor activation, extends the novel concept of partial agonism within the Cys-loop family, reveals novel aspects of partial agonism, and unmasks molecular actions of classically defined partial agonists. Unraveling mechanisms underlying partial responses has implications in the design of therapeutic compounds.
he effect of complexation of Cu ( II ) with P 6 A peptide and its nalogs on their thrombolytic activities

The complexation of Cu(II) with previously synthesized thrombolytic peptides, Pro-Ala-Lys (6), Arg-ProAla-Lys (7), Ala-Arg-Pro-Ala-Lys (8), Gly-Arg-Pro-Ala-Lys (9) and Gln-Arg-Pro-Ala-Lys (10), resulted in the formation of complexes, Cu(II)-(Pro-Ala-Lys) (6-Cu), Cu(II)-(Arg-Pro-Ala-Lys) (7-Cu), Cu(II)-(Ala-ArgPro-Ala-Lys) (8-Cu), Cu(II)-(Gly-Arg-Pro-Ala-Lys) (9-Cu) and Cu(II)-(Gln-Arg-Pro-Ala-Lys) (10-Cu), which was confirmed by UV-Vis, circular dichroism and ESI-MS analyses. Complexes (6–10)-Cu in normal saline (NS) were found to be able to assemble into aggregates, and the size of the aggregates were measured for the next eight consecutive days. It was found that on the 8th day, the diameters of (6–10)-Cu aggregates ranged from 179.21 ± 38.33 nm to 293.46 ± 51.07 nm. The Zeta potentials of (6–10)-Cu aggregates in NS were also examined and it was found that aggregates of (6, 8, 10)-Cu were negatively charged, and 7-Cu and 9-Cu were positively charged. The powders of (6–10)-Cu were analyzed by transmission electron microscopy and were found to have mean particle sizes of 8–15 nm. The in vitro euglobulin lysis, vasodilation and thrombolytic assays indicated that complexation with Cu(II) resulted in a significant increase in the activities of 6–10. The in vivo thrombolytic assays revealed that complexation with Cu(II) resulted in a significant enhancement in the in vivo thrombolytic activities for 6, 7, 8 and 10 at 10 mol/kg, and 9 at 1 mol/kg and 0.1 mol/kg, respectively. These findings suggested that the self-assembly of the Cu(II)–peptide complexes into nano-scale aggregates was beneficial in improving the thrombolytic activity a i of the peptides.
Judo combat: time-motion analysis and physiology

The understanding of time-motion and physiological responses to judo combat is important to training organization. This review was based on search results using the following terms: “judo and competition”, “judo and physiology”, “judo and randori”, and “judo and time-motion analysis”, “judo and combat”, “judo and match” and “judo and biochemestry”. The effort-pause ratio during judo combats is between 2:1 and 3:1, with 20s and 30s effort periods and 10s of pauses. Thus, judo combats rely on all three metabolisms, with the anaerobic alactic sytem being reponsible by the short duration powerful actions during technique applications, the anaerobic lactic system being responsible for the maintainance of high-intensity actions during longer periods (e.g., grip dispute), while the aerobic system is responsible for the recovery processes between high-intensity actions and matches. Training prescription must consider these demands and a muscle-specific action analysis may help to direct the proper approach to improve judo athletes’ performance. In general, lower-body is involved in short-term high-intensity actions during technique executions, while upper-body muscle groups are involved in both strength-endurance and power actions. As many muscle groups perform different actions during the match, a high cardiovascular demand is also observed in judo.
Horizon-switching Predictive Set-point Tracking under Input-increment Saturations and Persistent Disturbances

Predictive switching logic schemes are considered whereby a feedback-gain is switched-on at any time from a family of candidate feedback-gains so as to deal with the problem of set-point tracking in Asymptotically Null-controllable with Bounded Input (ANCBI) systems under input-increment saturations and persistent arbitrary bounded disturbances. It is constructively shown that such schemes do exist which ensure, along with good tracking performance, global asymptotic and semi-global exponential stability in the noiseless case, as well as bounded-noise bounded-state l∞-stability, whenever the disturbances enter the system in such a way to make these properties conceptually achievable.
Altered somatosensory processing in trigeminal neuralgia

Trigeminal neuralgia (TN) is a pain state characterized by intermittent unilateral pain attacks in one or several facial areas innervated by the trigeminal nerve. The somatosensory cortex is heavily involved in the perception of sensory features of pain, but it is also the primary target for thalamic input of nonpainful somatosensory information. Thus, pain and somatosensory processing are accomplished in overlapping cortical structures raising the question whether pain states are associated with alteration of somatosensory function itself. To test this hypothesis, we used functional magnetic resonance imaging to assess activation of primary (SI) and secondary (SII) somatosensory cortices upon nonpainful tactile stimulation of lips and fingers in 18 patients with TN and 10 patients with TN relieved from pain after successful neurosurgical intervention in comparison with 13 healthy subjects. We found that SI and SII activations in patients did neither depend on the affected side of TN nor differ between operated and nonoperated patients. However, SI and SII activations, but not thalamic activations, were significantly reduced in patients as compared to controls. These differences were most prominent for finger stimulation, an area not associated with TN. For lip stimulation SI and SII activations were reduced in patients with TN on the contra‐ but not on the ipsilateral side to the stimulus. These findings suggest a general reduction of SI and SII processing in patients with TN, indicating a long‐term modulation of somatosensory function and pointing to an attempt of cortical adaptation to potentially painful stimuli. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Electrical stimulation induces calcium‐dependent release of NGF from cultured Schwann cells

Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the present in vitro study, electrical stimulation (ES) was attempted to stimulate cultured SCs to release NGF. Our data showed that ES was capable of enhancing NGF release from cultured SCs. An electrical field (1 Hz, 5 V/cm) caused a 4.1‐fold increase in NGF release from cultured SCs. The ES‐induced NGF release is calcium dependent. Depletion of extracellular or/and intracellular calcium partially/ completely abolished the ES‐induced NGF release. Further pharmacological interventions showed that ES induces calcium influx through T‐type voltage‐gated calcium channels and mobilizes calcium from 1, 4, 5‐trisphosphate‐sensitive stores and caffeine/ryanodine‐sensitive stores, both of which contributed to the enhanced NGF release induced by ES. In addition, a calcium‐triggered exocytosis mechanism was involved in the ES‐induced NGF release from cultured SCs. These findings show the feasibility of using ES in stimulating SCs to release NGF, which holds great potential in promoting nerve regeneration by enhancing survival and outgrowth of damaged nerves, and is of great significance in nerve injury repair and neuronal tissue engineering. © 2009 Wiley‐Liss, Inc.
Surgical therapy of single peri-implantitis intrabony defects, by means of deproteinized bovine bone mineral with 10% collagen.

AIM To evaluate the efficacy of a reconstructive surgical procedure in single peri-implantitis infrabony defects. METHODS Seventy-five patients with one peri-implantitis crater-like lesion with pocket depth (PD) ≥ 6 mm, were included. Each defect was assigned to one characteristic class, by an independent examiner. After implant decontamination, defects were filled with deproteinized bovine bone mineral with 10% collagen. RESULTS At 1-year follow-up, four patients were lost and six implants removed. Treatment success, PD ≤ 5 mm and absence of suppuration/bleeding on probing (BOP), was obtained in 37 (52.1%) of the 71 implants examined. PD was significantly reduced by 2.92 ± 1.73 mm (p < 0.0001). BOP decreased from 71.5 ± 34.4% to 18.3 ± 28.6% (p < 0.0001). The mean number of deep pockets (≥ 6 mm) decreased from 3.00 ± 0.93 to 0.85 ± 1.35 (p < 0.0001). CONCLUSIONS These results confirm the possibility to successfully treat peri-implantitis lesions. There is lack of evidence of whether or not the resolution of the peri-implant disease is associated with the defect configuration. Due to the fact that complete resolution does not seem a predictable outcome, the clinical decision on whether implants should be treated should be based on several patient related elements.
Prestaties van de leerlingen van buitenlandse herkomst in België volgens de PISA-studie: vergelijking tussen de Franse Gemeenschap en de Vlaamse Gemeenschap

Prestaties van de leerlingen van buitenlandse herkomst in Belgie volgens de PISA-studie: vergelijking tussen de Franse Gemeenschap en de Vlaamse Gemeenschap Analyse van het onderzoek naar de slaagkansen van allochtone jongeren in het onderwijs van de Vlaamse en Franse Gemeenschap (2007) Reeks : Allochtone jongeren in het onderwijs Inhoud Slaagkansen van allochtone jongeren in het onderwijs zijn een belangrijke sleutelfactor voor een geslaagd integratieproces. Onlangs voerde het OESO een studie uit op basis van gegevens van het PISA. Uit deze studie blijkt dat de schoolresultaten van deze jongeren in het algemeen lager liggen dan het gemiddelde. In opdracht van de Koning Boudewijnstichting heeft GERME (ULB) een wetenschappelijke analyse van de resultaten van de PISA-onderzoek voor Belgie uitgevoerd.
Adherence: a review of education, research, practice and policy in Australia

Community pharmacists are well placed to deliver adherence support services as well as other pharmaceutical services to patients. They are often the last point of contact with patients collecting medicines in the healthcare chain, and they tend to be visited by patients on a regular basis to collect prescription medicines. They have the opportunity to reinforce information already received from other health practitioners, provide further information and monitor adherence to therapy. The past decade has seen an increase in focus on the importance of adherence to therapy, not only in the higher education sector, but also in government policy and community pharmacy practice. Adherence monitoring and promotion has not only become the foundation of courses taught in pharmacy schools, but has become an essential component of disease management and pharmaceutical services delivered by community pharmacists. Aims This article aims to describe the education, research, practice and policy in the area of adherence to therapy in Australia with a focus on community pharmacists. Methods A search of MEDLINE and International Pharmaceutical Abstracts as well as hand searches of the bibliographies of retrieved articles was conducted for the period 2000-2008. All pharmacy schools in Australia were also contacted to obtain information on the patient adherence to therapy content of their courses. Results Ten studies met the inclusion criteria. Only one study had a specific adherence focus, with the remainder including adherence support and monitoring as part of the overall interventions delivered by the community pharmacists. In the majority of cases the interventions resulted in an improvement in patients’ adherence to therapy. The research was supported by government and pharmacy professional organisation initiatives in the area of cognitive pharmaceutical services. All universities which responded delivered specific patient adherence courses. Conclusions Australian pharmacy schools are educating cohorts of students who will have the skills to monitor and support patient medication adherence in the context of contemporary pharmacy practice. This is supported by research evidence, government policy and fits well into the move to expand community pharmacy services to include chronic disease state management and primary health care.
Preserved fine-tuning of face perception and memory: evidence from the own-race bias in high- and low-performing older adults

Previous research suggests specific deficits in face perception and memory in older adults, which could reflect a dedifferentiation in the context of a general broadening of cognitive architecture with advanced age. Such dedifferentiation could manifest in a less specialized face processing system. A promising tool to investigate the fine-tuning of face processing in older age is the own-race bias (ORB), a phenomenon reflecting more accurate memory for own-relative to other-race faces, which is related to an expertise-based specialization of early perceptual stages. To investigate whether poor face memory in older age is accompanied by reduced expertise-based specialization of face processing, we assessed event-related brain potential correlates of the ORB in high- vs. low-performing older adults (mean age = 69 years; N = 24 per group). Intriguingly, both older groups demonstrated an equivalent pattern of a behavioral ORB, and a parallel increase in N170 for other-race faces, reflecting less efficient early perceptual processing for this face category. Group differences only emerged independent of face ethnicity: whereas low-performers exhibited a right-lateralized N170, high-performers showed a more bilateral response. This finding may suggest a compensatory mechanism counteracting age-related decline in face perception enabling more efficient encoding into memory in high performers. Overall, our results demonstrate that even a less efficient face processing system in older adults can exhibit preserved expertise-related specialization toward own-race faces.
Manganese Specificity Determinants in the ArabidopsisMetal/H+ Antiporter CAX2*

In plants and fungi, vacuolar transporters help remove potentially toxic cations from the cytosol. Metal/H+ antiporters are involved in metal sequestration into the vacuole. However, the specific transport properties and the ability to manipulate these transporters to alter substrate specificity are poorly understood. The Arabidopsis thaliana cation exchangers, CAX1 and CAX2, can both transport Ca2+ into the vacuole. There are 11 CAX-like transporters in Arabidopsis; however, CAX2 was the only characterized CAX transporter capable of vacuolar Mn2+ transport when expressed in yeast. To determine the domains within CAX2 that mediate Mn2+ specificity, six CAX2 mutants were constructed that contained different regions of the CAX1 transporter. One class displayed no alterations in Mn2+ or Ca2+ transport, the second class showed a reduction in Ca2+ transport and no measurable Mn2+transport, and the third mutant, which contained a 10-amino acid domain from CAX1 (CAX2-C), showed no reduction in Ca2+ transport and a complete loss of Mn2+ transport. The subdomain analysis of CAX2-C identified a 3-amino acid region that is responsible for Mn2+ specificity of CAX2. This study provides evidence for the feasibility of altering substrate specificity in a metal/H+ antiporter, an important family of transporters found in a variety of organisms.
An Independent Evaluation of Subspace Face Recognition Algorithms

This paper explores a comparative study of both the linear and kernel implementations of three of the most popular Appearance-based Face Recognition projection classes, these being the methodologies of Principal Component Analysis, Linear Discriminant Analysis and Independent Component Analysis. The experimental procedure provides a platform of equal working conditions and examines the ten algorithms in the categories of expression, illumination, occlusion and temporal delay. The results are then evaluated based on a sequential combination of assessment tools that facilitate both intuitive and statistical decisiveness among the intra and interclass comparisons. The best categorical algorithms are then incorporated into a hybrid methodology, where the advantageous effects of fusion strategies are considered.
Attitudes about Tuberculosis Prevention in the Elimination Phase: A Survey among Physicians in Germany

Background Targeted and stringent measures of tuberculosis prevention are necessary to achieve the goal of tuberculosis elimination in countries of low tuberculosis incidence. Methods We ascertained the knowledge about tuberculosis risk factors and stringency of tuberculosis prevention measures by a standardized questionnaire among physicians in Germany involved in the care of individuals from classical risk groups for tuberculosis. Results 510 physicians responded to the online survey. Among 16 risk factors immunosuppressive therapy, HIV-infection and treatment with TNF-antagonist were thought to be the most important risk factors for the development of tuberculosis in Germany. Exposure to a patient with tuberculosis ranked on the 10th position. In the event of a positive tuberculin-skin-test or interferon-γ release assay only 50%, 40%, 36% and 25% of physicians found that preventive chemotherapy was indicated for individuals undergoing tumor necrosis factor-antagonist therapy, close contacts of tuberculosis patients, HIV-infected individuals and migrants, respectively. Conclusions A remarkably low proportion of individuals with latent infection with Mycobacterium tuberculosis belonging to classical risk groups for tuberculosis are considered candidates for preventive chemotherapy in Germany. Better knowledge about the risk for tuberculosis in different groups and more stringent and targeted preventive interventions will probably be necessary to achieve tuberculosis elimination in Germany.
From Single Cells to Tissues: Interactions between the Matrix and Human Breast Cells in Real Time

Background Mammary gland morphogenesis involves ductal elongation, branching, and budding. All of these processes are mediated by stroma - epithelium interactions. Biomechanical factors, such as matrix stiffness, have been established as important factors in these interactions. For example, epithelial cells fail to form normal acinar structures in vitro in 3D gels that exceed the stiffness of a normal mammary gland. Additionally, heterogeneity in the spatial distribution of acini and ducts within individual collagen gels suggests that local organization of the matrix may guide morphogenesis. Here, we quantified the effects of both bulk material stiffness and local collagen fiber arrangement on epithelial morphogenesis. Results The formation of ducts and acini from single cells and the reorganization of the collagen fiber network were quantified using time-lapse confocal microscopy. MCF10A cells organized the surrounding collagen fibers during the first twelve hours after seeding. Collagen fiber density and alignment relative to the epithelial surface significantly increased within the first twelve hours and were a major influence in the shaping of the mammary epithelium. The addition of Matrigel to the collagen fiber network impaired cell-mediated reorganization of the matrix and increased the probability of spheroidal acini rather than branching ducts. The mechanical anisotropy created by regions of highly aligned collagen fibers facilitated elongation and branching, which was significantly correlated with fiber organization. In contrast, changes in bulk stiffness were not a strong predictor of this epithelial morphology. Conclusions Localized regions of collagen fiber alignment are required for ductal elongation and branching suggesting the importance of local mechanical anisotropy in mammary epithelial morphogenesis. Similar principles may govern the morphology of branching and budding in other tissues and organs.
A distributed catalog for heterogeneous distributed database resources

To support a distributed, heterogeneous computing environment, an inter-system catalog protocol is needed so that remote resources can be located, used, and maintained with little human intervention. This paper describes a scalable catalog framework, which is an extension of previous work in a distributed relational DBMS research prototype called R*. This work builds on the R* concepts to accommodate heterogeneity, to handle partitioned and replicated data, to support non-DBMS resource managers, and to enhance catalog access performance and system extensibility. <<ETX>>
Tomato RAV Transcription Factor Is a Pivotal Modulator Involved in the AP2/EREBP-Mediated Defense Pathway1[W][OA]

Ralstonia solanacearum is the causal agent of bacterial wilt (BW), one of the most important bacterial diseases worldwide. We used cDNA microarray to survey the gene expression profile in transgenic tomato (Solanum lycopersicum) overexpressing Arabidopsis (Arabidopsis thaliana) CBF1 (AtCBF1), which confers tolerance to BW. The disease-resistant phenotype is correlated with constitutive expression of the Related-to-ABI3/VP1 (RAV) transcription factor, ethylene-responsive factor (ERF) family genes, and several pathogenesis-related (PR) genes. Using a transient assay system, we show that tomato RAV2 (SlRAV2) can transactivate the reporter gene driven by the SlERF5 promoter. Virus-induced gene silencing of SlERF5 and SlRAV2 in AtCBF1 transgenic and BW-resistant cultivar Hawaii 7996 plants gave rise to plants with enhanced susceptibility to BW. Constitutive overexpression of SlRAV2 in transgenic tomato plants induced the expression of SlERF5 and PR5 genes and increased BW tolerance, while knockdown of expression of SlRAV2 inhibited SlERF5 and PR5 gene expression under pathogen infection and significantly decreased BW tolerance. In addition, transgenic tomato overexpressing SlERF5 also accumulated higher levels of PR5 transcripts and displayed better tolerance to pathogen than wild-type plants. From these results, we conclude that SlERFs may act as intermediate transcription factors between AtCBF1 and PR genes via SlRAV in tomato, which results in enhanced tolerance to BW.