numerical investigation of wire clamp contact for a drawing machine

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Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

: Motor symptoms of Parkinson's Disease (PD) are associated with dopamine deficits and pathological oscillation of basal ganglia (BG) neurons in the β range ([12-30] Hz). However, how dopamine depletion affects the oscillation dynamics of BG nuclei is still unclear. With a spiking neurons model, we here capture the features of BG nuclei interactions leading to oscillations in dopamine-depleted condition. We highlight that both the loop between subthalamic nucleus (STN) and Globus Pallidus pars externa (GPe) and the loop between striatal fast spiking and medium spiny neurons and GPe display resonances in the β range, and synchronize to a common β frequency through interaction. Crucially, the synchronization depends on dopamine depletion: the two loops are largely independent for high levels of dopamine, but progressively synchronize as dopamine is depleted due to the increased strength of the striatal loop. The model is validated against recent experimental reports on the role of cortical inputs, STN and GPe activity in the generation of β oscillations. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustained β oscillations in PD subjects, and explain how this interplay depends on the level of dopamine. This paves the way to the design of therapies specifically addressing the onset of pathological β oscillations

Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo

Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilage in vitro. Furthermore, upon in vivo transplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using this in vivo model, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche. CB ossicles were regularly observed upon transplantation. Compared with BM ossicles, CB ossicles showed a predominance of red marrow over yellow marrow, as demonstrated by histomorphological analyses and the number of hematopoietic cells isolated within ossicles. Marrow cavities from CB and BM ossicles included donor-derived CD146-expressing osteoprogenitors and host-derived mature hematopoietic cells, clonogenic lineage-committed progenitors and HSCs. Furthermore, human CD34+ cells transplanted into ossicle-bearing mice engrafted and maintained human HSCs in the niche. Our data indicate that CB- BFs are able to recapitulate the conditions by which the bone marrow microenvironment is formed and establish complete HSC niches, which are functionally supportive of hematopoietic tissue

Dureza de resinas acrílicas para base de prótese e reembasamento imediato

INTRODUCTION: The hardness of denture base materials may undergo changes due to continued polymerization reaction and water uptake. However, the extent to which these processes affect the hardness of materials is still unclear. OBJECTIVE: In this study, the degree of conversion of two hard chair-side reline resins (Duraliner II-D and Kooliner-K) and one heat-cured acrylic resin (Lucitone 550-L) was evaluated indirectly by measuring the surface hardness. The effect of immersion in water on this property was also analyzed. MATERIALS AND METHODS: After processing following the manufacturers' instructions, specimens (5mm diameter and 2mm thickness) were dry stored at room temperature and the Vickers hardness (VHN) was measured with a hardness tester after 0, 2, 7, 30 and 90 days. Specimens were then immersed in water at 37ºC and hardness was evaluated after the same time intervals. Five specimens were prepared for each material. Data were analyzed by Kruskal-Wallis test (P=.01). RESULTS: When dry stored, material L showed an increase in hardness (P;.01). After 2-day water storage, all materials showed a significant reduction in hardness (PINTRODUÇÃO: A dureza das resinas para base de prótese e para reembasamento imediato pode apresentar alterações devido à polimerização continuada e absorção de água. Entretanto, a magnitude do efeito de cada um desses processos ainda não foi definida. OBJETIVO: Neste estudo, o grau de conversão de duas resinas autopolimerizáveis para reembasamento (Duraliner II-D and Kooliner-K) e de uma resina termopolimerizável para base de prótese (Lucitone 550-L) foi avaliado, indiretamente, por meio da mensuração da dureza. O efeito da imersão em água sobre essa propriedade também foi analisado. MATERIAL E MÉTODOS: Após a polimerização, amostras (diâmetro - 5 mm; espessura - 2 mm) foram armazenadas a seco em temperatura ambiente e a dureza Vickers (VHN) foi mensurada após 0, 2, 7, 30 e 90 dias. As amostras foram, então, imersas em água a 37º C e a dureza foi avaliada nos períodos citados. Cinco amostras foram preparadas para cada material. Os resultados foram analisados utilizando-se o teste de Kruskal-Wallis (P=.01). RESULTADOS: Para o armazenamento a seco, o material L apresentou aumento significativo na dureza (P;.01). Após 2 dias de armazenamento em água, todos os materiais apresentaram redução significativa na dureza (

Clustering of galaxies around GRB sight-lines

There is evidence of an overdensity of strong intervening MgII absorption line systems distributed along the lines of sight towards GRB afterglows relative to quasar sight-lines. If this excess is real, one should also expect an overdensity of field galaxies around GRB sight-lines, as strong MgII tends to trace these sources. In this work, we test this expectation by calculating the two point angular correlation function of galaxies within 120$^{\prime\prime}$ ($\sim470~h_{71}^{-1}~\mathrm{Kpc}$ at $\langle z\rangle \sim0.4$) of GRB afterglows. We compare the Gamma-ray burst Optical and Near-infrared Detector (GROND) GRB afterglow sample -- one of the largest and most homogeneous samples of GRB fields -- with galaxies and AGN found in the COSMOS-30 photometric catalog. We find no significant signal of anomalous clustering of galaxies at an estimated median redshift of $z\sim0.3$ around GRB sight-lines, down to $K_{\mathrm{AB}}<19.3$. This result is contrary to the expectations from the MgII excess derived from GRB afterglow spectroscopy, although many confirmed galaxy counterparts to MgII absorbers may be too faint to detect in our sample -- especially those at $z>1$. We note that the addition of higher sensitivity Spitzer IRAC or HST WFC3 data for even a subset of our sample would increase this survey's depth by several orders of magnitude, simultaneously increasing statistics and enabling the investigation of a much larger redshift space.}Comment: 10 pages, 6 figures. A&A accepte

Respiratory function in cybrid cell lines carrying European mtDNA haplogroups: implications for Leber's hereditary optic neuropathy

AbstractThe possibility that some combinations of mtDNA polymorphisms, previously associated with Leber's hereditary optic neuropathy (LHON), may affect mitochondrial respiratory function was tested in osteosarcoma-derived transmitochondrial cytoplasmic hybrids (cybrids). In this cellular system, in the presence of the same nuclear background, different exogenous mtDNAs are used to repopulate a parental cell line previously devoid of its original mtDNA. No detectable differences in multiple parameters exploring respiratory function were observed when mtDNAs belonging to European haplogroups X, H, T and J were used. Different possible explanations for the previously established association between haplogroup J and LHON 11778/ND4 and 14484/ND6 pathogenic mutations are discussed, including the unconventional proposal that mtDNA haplogroup J may exert a protective rather than detrimental effect

A magnetar powering the ordinary monster GRB 130427A?

We present the analysis of the extraordinarily bright Gamma-Ray Burst (GRB) 130427A under the hypothesis that the GRB central engine is an accretion-powered magnetar. In this framework, initially proposed to explain GRBs with precursor activity, the prompt emission is produced by accretion of matter onto a newly-born magnetar, and the observed power is related to the accretion rate. The emission is eventually halted if the centrifugal forces are able to pause accretion. We show that the X-ray and optical afterglow is well explained as the forward shock emission with a jet break plus a contribution from the spin-down of the magnetar. Our modelling does not require any contribution from the reverse shock, that may still influence the afterglow light curve at radio and mm frequencies, or in the optical at early times. We derive the magnetic field ($B\sim 10^{16}$ G) and the spin period ($P\sim 20$ ms) of the magnetar and obtain an independent estimate of the minimum luminosity for accretion. This minimum luminosity results well below the prompt emission luminosity of GRB 130427A, providing a strong consistency check for the scenario where the entire prompt emission is the result of continuous accretion onto the magnetar. This is in agreement with the relatively long spin period of the magnetar. GRB 130427A was a well monitored GRB showing a very standard behavior and, thus, is a well-suited benchmark to show that an accretion-powered magnetar gives a unique view of the properties of long GRBs.Comment: 5 pages, 1 figure, accepted for publication in MNRAS Letter

3,5-Diiodo-L-Thyronine Modifies the Lipid Droplet Composition in a Model of Hepatosteatosis

Background/Aims: Fatty acids are the main energy stores and the major membrane components of the cells. In the hepatocyte, fatty acids are esterified to triacylglycerols (TAGs) and stored in lipid droplets (LDs). The lipid lowering action of 3,5-diiodo-L-thyronine (T 2 ) on an in vitro model of hepatosteatosis was investigated in terms of fatty acid and protein content of LDs, lipid oxidation and secretion. Methods: FaO cells were exposed to oleate/ palmitate, then treated with T 2 . Results: T 2 reduced number and size of LDs, and modified their acyl composition by decreasing the content of saturated (SFA) vs monounsaturated (MUFA) fatty acids thus reversing the SFA/MUFA ratio. The expression of the LD-associated proteins adipose differentiation-related protein (ADRP), oxidative tissue-enriched PAT protein (OXPAT), and adipose triglyceride lipase (ATGL) was increased in 'steatotic' cells and further up-regulated by T 2 . Moreover, T 2 stimulated the mitochondrial oxidation by up-regulating carnitine-palmitoyl-transferase (CPT1), uncoupling protein 2 (UCP2) and very long-chain acylcoenzyme A dehydrogenase (VLCAD). Conclusions: T 2 leads to mobilization of TAGs from LDs and stimulates mitochondrial oxidative metabolism of fatty acids, in particular of SFAs, and thus enriches of MUFAs the LDs. This action may protect the hepatocyte from excess of SFAs that are more toxic than MUFAs

Near Normalization of Metabolic and Functional Features of the Central Nervous System in Type 1 Diabetic Patients With End-Stage Renal Disease After Kidney-Pancreas Transplantation

OBJECTIVE The pathogenesis of brain disorders in type 1 diabetes (T1D) is multifactorial and involves the adverse effects of chronic hyperglycemia and of recurrent hypoglycemia. Kidney-pancreas (KP), but not kidney alone (KD), transplantation is associated with sustained normoglycemia, improvement in quality of life, and reduction of morbidity/mortality in diabetic patients with end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS The aim of our study was to evaluate with magnetic resonance imaging and nuclear magnetic resonance spectroscopy (1H MRS) the cerebral morphology and metabolism of 15 ESRD plus T1D patients, 23 patients with ESRD plus T1D after KD (n = 9) and KP (n = 14) transplantation, and 8 age-matched control subjects. RESULTS Magnetic resonance imaging showed a higher prevalence of cerebrovascular disease in ESRD plus T1D patients (53% [95% CI 36–69]) compared with healthy subjects (25% [3–6], P = 0.04). Brain 1H MRS showed lower levels of N-acetyl aspartate (NAA)-to-choline ratio in ESRD plus T1D, KD, and KP patients compared with control subjects (control subjects vs. all, P < 0.05) and of NAA-to-creatine ratio in ESRD plus T1D compared with KP and control subjects (ESRD plus T1D vs. control and KP subjects, P ≤ 0.01). The evaluation of the most common scores of psychological and neuropsychological function showed a generally better intellectual profile in control and KP subjects compared with ESRD plus T1D and KD patients. CONCLUSIONS Diabetes and ESRD are associated with a precocious form of brain impairment, chronic cerebrovascular disease, and cognitive decline. In KP-transplanted patients, most of these features appeared to be near normalized after a 5-year follow-up period of sustained normoglycemia

Prolonged, Low-Dose Anti-Thymocyte Globulin, Combined with CTLA4-Ig, Promotes Engraftment in a Stringent Transplant Model

Background: Despite significant nephrotoxicity, calcineurin inhibitors (CNIs) remain the cornerstone of immunosuppression in solid organ transplantation. We, along with others, have reported tolerogenic properties of anti-thymocyte globulin (ATG, Thymoglobulin®), evinced by its ability both to spare Tregs from depletion in vivo and, when administered at low, non-depleting doses, to expand Tregs ex vivo. Clinical trials investigating B7/CD28 blockade (LEA29Y, Belatacept) in kidney transplant recipients have proven that the replacement of toxic CNI use is feasible in selected populations. Methods: Rabbit polyclonal anti-murine thymocyte globulin (mATG) was administered as induction and/or prolonged, low-dose therapy, in combination with CTLA4-Ig, in a stringent, fully MHC-mismatched murine skin transplant model to assess graft survival and mechanisms of action. Results: Prolonged, low-dose mATG, combined with CTLA4-Ig, effectively promotes engraftment in a stringent transplant model. Our data demonstrate that mATG achieves graft acceptance primarily by promoting Tregs, while CTLA4-Ig enhances mATG function by limiting activation of the effector T cell pool in the early stages of treatment, and by inhibiting production of anti-rabbit antibodies in the maintenance phase, thereby promoting regulation of alloreactivity. Conclusion: These data provide the rationale for development of novel, CNI-free clinical protocols in human transplant recipients