Handwritten Script Recognition using DCT, Gabor Filter and Wavelet Features at Line Level

In a country like India where more number of scripts are in use, automatic identification of printed and handwritten script facilitates many important applications including sorting of document images and searching online archives of document images. In this paper, a multiple feature based approach is presented to identify the script type of the collection of handwritten documents. Eight popular Indian scripts are considered here. Features are extracted using Gabor filters, Discrete Cosine Transform, and Wavelets of Daubechies family. Experiments are performed to test the recognition accuracy of the proposed system at line level for bilingual scripts and later extended to trilingual scripts. We have obtained 100% recognition accuracy for bi-scripts at line level. The classification is done using k-nearest neighbour classifier

Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer

Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in causespecific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = .45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.This work was supported by NIH grants RO1 CA56678, RO1 CA114524, and P50 CA97186; additional support was provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute

Nonuniform Cardiac Denervation Observed by 11C-meta-Hydroxyephedrine PET in 6-OHDA-Treated Monkeys

Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog 11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia

High LRRK2 Levels Fail to Induce or Exacerbate Neuronal Alpha-Synucleinopathy in Mouse Brain

The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2 (LRRK2) is one of the most frequently identified genetic causes of Parkinson’s disease (PD). Clinically, LRRK2(G2019S) carriers with PD and idiopathic PD patients have a very similar disease with brainstem and cortical Lewy pathology (α-synucleinopathy) as histopathological hallmarks. Some patients have Tau pathology. Enhanced kinase function of the LRRK2(G2019S) mutant protein is a prime suspect mechanism for carriers to develop PD but observations in LRRK2 knock-out, G2019S knock-in and kinase-dead mutant mice suggest that LRRK2 steady-state abundance of the protein also plays a determining role. One critical question concerning the molecular pathogenesis in LRRK2(G2019S) PD patients is whether α-synuclein (aSN) has a contributory role. To this end we generated mice with high expression of either wildtype or G2019S mutant LRRK2 in brainstem and cortical neurons. High levels of these LRRK2 variants left endogenous aSN and Tau levels unaltered and did not exacerbate or otherwise modify α-synucleinopathy in mice that co-expressed high levels of LRRK2 and aSN in brain neurons. On the contrary, in some lines high LRRK2 levels improved motor skills in the presence and absence of aSN-transgene-induced disease. Therefore, in many neurons high LRRK2 levels are well tolerated and not sufficient to drive or exacerbate neuronal α-synucleinopathy

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

K*(892)(0) and phi(1020)meson production at high transverse momentum in pp and Pb-Pb collisions at root sNN=2.76 TeV

The production of K∗(892)0 and φ(1020) mesons in proton-proton (pp) and lead-lead (Pb-Pb) collisions at √sNN = 2.76 TeV has been analyzed using a high luminosity data sample accumulated in 2011 with the ALICE detector at the Large Hadron Collider (LHC). Transverse momentum (pT) spectra have been measured for K∗(892)0 and φ(1020) mesons via their hadronic decay channels for pT up to 20 GeV/c. The measurements in pp collisions have been compared to model calculations and used to determine the nuclear modification factor and particle ratios. The K∗(892)0/K ratio exhibits significant reduction from pp to central Pb-Pb collisions, consistent with the suppression of the K∗(892)0 yield at low pT due to rescattering of its decay products in the hadronic phase. In central Pb-Pb collisions the pT dependent φ(1020)/π and K∗(892)0/π ratios show an enhancement over pp collisions for pT ≈ 3 GeV/c, consistent with previous observations of strong radial flow. At high pT, particle ratios in Pb-Pb collisions are similar to those measured in pp collisions. In central Pb-Pb collisions, the production of K∗(892)0 and φ(1020) mesons is suppressed for pT &gt; 8 GeV/c. This suppression is similar to that of charged pions, kaons, and protons, indicating that the suppression does not depend on particle mass or flavor in the light quark sector

Flow Dominance and Factorization of Transverse Momentum Correlations in Pb-Pb Collisions at the LHC

We present the first measurement of the two-particle transverse momentum differential correlation function, P2≡ ΔpTΔpT/ pT2, in Pb-Pb collisions at sNN=2.76 TeV. Results for P2 are reported as a function of the relative pseudorapidity (Δη) and azimuthal angle (Δφ) between two particles for different collision centralities. The Δφ dependence is found to be largely independent of Δη for |Δη|≥0.9. In the 5% most central Pb-Pb collisions, the two-particle transverse momentum correlation function exhibits a clear double-hump structure around Δφ=π (i.e., on the away side), which is not observed in number correlations in the same centrality range, and thus provides an indication of the dominance of triangular flow in this collision centrality. Fourier decompositions of P2, studied as a function of the collision centrality, show that correlations at |Δη|≥0.9 can be well reproduced by a flow ansatz based on the notion that measured transverse momentum correlations are strictly determined by the collective motion of the system

Particle identification in ALICE : a Bayesian approach

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