Higher ramification and varieties of secant divisors on the generic curve

For a smooth projective curve, the cycles of e-secant k-planes are among the most studied objects in classical enumerative geometry and there are well-known formulas due to Castelnuovo, Cayley and MacDonald concerning them. Despite various attempts, surprisingly little is known about the enumerative validity of such formulas. The aim of this paper is to completely clarify this problem in the case of the generic curve C of given genus. Using degeneration techniques and a few facts about the birational geometry of moduli spaces of stable pointed curves we determine precisely under which conditions the cycle of e-secant k-planes in non-empty and we compute its dimension. We also precisely determine the dimension of the variety of linear series on C carrying e-secant k-planes. In a different direction, in the last part of the paper we study the distribution of ramification points of the powers of a line bundle on C having prescribed ramification at a given point.Comment: 25 pages. Numerous changes suggested by the referee, several proofs explained in more detail. To appear in the Journal of the London Mathematical Societ

Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis

This project was supported through a studentship awarded by the Plymouth University Peninsula Schools of Medicine and Dentistry.Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson's disease (PD).The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use. The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress. Differentiated SH-SY5Y neuroblastoma cells were exposed to the PD relevant mitochondrial complex 1 inhibitor 1-methyl- 4-phenylpyridinium iodide (MPP+). We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1a (PGC-1a), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content. Co-application of Δ9- THC with pioglitazone further increased the neuroprotection against MPP+ toxicity as compared to pioglitazone treatment alone. Furthermore, using lentiviral knock down of the PPARγ receptor we showed that, unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress. We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment.Publisher PDFPeer reviewe

Pancreas deficiency modifies bone development in the ovine fetus near term.

Hormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-CT and an electromagnetic three-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomized fetuses compared to control fetuses, limb lengths were shorter, and trabecular (Tb) bone in the metatarsi showed greater bone volume fraction, Tb thickness, degree of anisotropy and porosity, and lower fractional bone surface area and Tb spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed the growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth

Patterns of dominant flows in the world trade web

The large-scale organization of the world economies is exhibiting increasingly levels of local heterogeneity and global interdependency. Understanding the relation between local and global features calls for analytical tools able to uncover the global emerging organization of the international trade network. Here we analyze the world network of bilateral trade imbalances and characterize its overall flux organization, unraveling local and global high-flux pathways that define the backbone of the trade system. We develop a general procedure capable to progressively filter out in a consistent and quantitative way the dominant trade channels. This procedure is completely general and can be applied to any weighted network to detect the underlying structure of transport flows. The trade fluxes properties of the world trade web determines a ranking of trade partnerships that highlights global interdependencies, providing information not accessible by simple local analysis. The present work provides new quantitative tools for a dynamical approach to the propagation of economic crises

Preventing preschool mental health problems: Population-based cluster randomized controlled trial

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Objective Prevention of child behavior problems may reduce later mental health problems. We compared the effectiveness, at the population level, of an efficacious targeted prevention program alone or following a universal parenting program. Method Three arm, cluster randomized controlled trial. 1353 primary caregivers and healthy eight-month-old babies recruited July 2010 to January 2011 from well-child centers (randomization unit). Primary outcome: Child Behavior Checklist (CBCL) externalizing and internalizing scales* at child age three and 4.5 years. Secondary outcomes: Parenting Behavior Checklist* and over-involved/protective parenting (primary caregiver report). Secondary caregivers completed starred measures at age three. Results Retention was 76% and 77% at ages three and 4.5 years, respectively. At three years, intention-to-treat analyses found no statistically significant differences (adjusted mean difference (95% CI; p-value)) for externalizing (Targeted versus Usual Care -0.2 (-1.7 to 1.2; p= 0.76); Combined versus Usual Care 0.4 (-1.1 to 1.9; p=0.60)) or internalizing behavior problems (Targeted versus Usual Care 0.2 (-1.2 to 1.6; p= 0.76); Combined versus Usual Care 0.4 (-1.1 to 2.0; p=0.58)). Primary outcomes were similar at 4.5 years. At three years, primary and secondary caregivers reported less over-involved/protective parenting in both the Combined and Targeted versus Usual Care arm; secondary caregivers also reported less harsh discipline in the Combined and Targeted versus Usual Care arm. Mean program costs per family were $A218 (Targeted arm) and A$682 (Combined arm). Conclusion When translated to the population level by existing staff, pre-existing programs appeared ineffective in improving child behavior, alone or in combination, but improved parenting

Quantitative Susceptibility Mapping (QSM) is Sensitive to Hippocampal and Subcortical Gray Matter Changes in Temporal Lobe Epilepsy

Although temporal lobe epilepsy (TLE) results in widespread changes in MRI measures of tissue volume, diffusion and functional connectivity, changes in tissue composition in TLE have not been investigated with MRI. Quantitative susceptibility mapping (QSM) is sensitive to changes in tissue composition, in particular to iron and myelin. Here, we show for the first time that QSM is sensitive to gray matter abnormalities in 31patients with temporal lobe epilepsy (TLE) compared to 23 healthy controls, and showed significant susceptibility changes in the hippocampus in left TLE patients, and in the bilateral thalamus in both left and right TLE

The neural basis of fatigue in multiple sclerosis: A multimodal MRI approach

BACKGROUND: Fatigue is a frequent disabling symptom in multiple sclerosis (MS), but its pathophysiology remains incompletely understood. This study aimed to explore the underlying neural basis of fatigue in patients with MS. METHODS: We enrolled 60 consecutive patients with MS and 60 healthy controls (HC) matched on age, sex, and education. Fatigue was assessed using the Portuguese version of the Modified Fatigue Impact Scale (MFIS). All participants underwent 3T brain MRI (conventional and diffusion tensor imaging [DTI] sequences). White matter (WM) focal lesions were identified and T1/T2 lesion volumes were computed. Tract-based spatial statistics were applied for voxel-wise analysis of DTI metrics fractional anisotropy and mean diffusivity (MD) on normal-appearing WM (NAWM). Using Freesurfer software, total and regional volumes of cortical and subcortical gray matter (GM) were calculated. RESULTS: Compared to HC, patients with MS scored significantly higher on MFIS (33.8 ± 19.7 vs 16.5 ± 15.1, p < 0.001). MFIS scores were not significantly correlated with T1/T2 lesion volumes, total GM volume, or any regional volume of cortical and subcortical GM. Significant correlations were found between global scores of MFIS and MD increase of the NAWM skeleton, including corona radiata, internal capsule, external capsule, corticospinal tract, cingulum, corpus callosum, fornix, superior longitudinal fasciculus, superior fronto-occipital fasciculus, sagittal stratum, posterior thalamic radiation, cerebral peduncle, and uncinate fasciculus. CONCLUSIONS: In this study, fatigue was associated with widespread NAWM damage but not with lesion load or GM atrophy. Functional disconnection, caused by diffuse microstructural WM damage, might be the main neural basis of fatigue in MS.info:eu-repo/semantics/publishedVersio

Clinical presentation and survival of smear-positive pulmonary tuberculosis patients of a University General Hospital in a developing country

From January 1995 to August 1997 we evaluated prospectively the clinical presentation, laboratory findings and short-term survival of smear-positive pulmonary tuberculosis (TB) patients who sought care at our hospital. After providing informed, written consent, the patients were interviewed and laboratory tests were performed. Information about survivorship and death was collected through September 1998. Eighty-six smear-positive pulmonary TB patients were enrolled; 26.7% were HIV-seropositive. Seventeen HIV-seronegative pulmonary TB patients (19.8%) presented chronic diseases in addition to TB. In the multiple logistic regression analysis a CD4+ cell count or = 50 years were independently associated with decreased survival. Among HIV-seronegative persons, the presence of an additional disease increased the risk of death of almost six-fold. Use of antiretroviral drugs was associated with a lower risk of death among HIV-seropositive smear-positive pulmonary TB patients (RH = 0.32, 95% CI 0.10-0.92). In our study smear-positive pulmonary TB patients had a low short-term survival rate that was strongly associated with HIV infection, age and co-morbidities. Therapy with antiretroviral drugs reduced the short-term risk of death among HIV-seropositive patients after TB diagnosis

FLORA: a novel method to predict protein function from structure in diverse superfamilies

Predicting protein function from structure remains an active area of interest, particularly for the structural genomics initiatives where a substantial number of structures are initially solved with little or no functional characterisation. Although global structure comparison methods can be used to transfer functional annotations, the relationship between fold and function is complex, particularly in functionally diverse superfamilies that have evolved through different secondary structure embellishments to a common structural core. The majority of prediction algorithms employ local templates built on known or predicted functional residues. Here, we present a novel method (FLORA) that automatically generates structural motifs associated with different functional sub-families (FSGs) within functionally diverse domain superfamilies. Templates are created purely on the basis of their specificity for a given FSG, and the method makes no prior prediction of functional sites, nor assumes specific physico-chemical properties of residues. FLORA is able to accurately discriminate between homologous domains with different functions and substantially outperforms (a 2–3 fold increase in coverage at low error rates) popular structure comparison methods and a leading function prediction method. We benchmark FLORA on a large data set of enzyme superfamilies from all three major protein classes (α, β, αβ) and demonstrate the functional relevance of the motifs it identifies. We also provide novel predictions of enzymatic activity for a large number of structures solved by the Protein Structure Initiative. Overall, we show that FLORA is able to effectively detect functionally similar protein domain structures by purely using patterns of structural conservation of all residues