On the Distribution of the Sum of n Non-Identically Distributed Uniform Random Variables

The distribution of the sum of independent identically distributed uniform random variables is well-known. However, it is sometimes necessary to analyze data which have been drawn from different uniform distributions. By inverting the characteristic function, we derive explicit formulae for the distribution of the sum of n non-identically distributed uniform random variables in both the continuous and the discrete case. The results, though involved, have a certain elegance. As examples, we derive from our general formulae some special cases which have appeared in the literature.Comment: 20 page

Estimating and Adjusting Field Quality in Superconducting accelerator magnets

The experience with estimating and adjusting field quality in RHIC (Relativistic Heavy Ion Collider) and SSC (Superconducting Super Collider) magnets is discussed. An alternate approach which makes a better estimate for systematic and random values of harmonics is presented

On the Multivariate Normal Hazard

AbstractIt is well known that the hazard rate of a univariate normal distribution is increasing. In this paper, we prove that the hazard gradient, in the case of general multivariate normal distribution, is increasing in the sense of Johnson and Kotz

Long-term therapy with elamipretide normalizes activation of the mitochondrial signal transducer and activator of transcription 3 (mstat3) in of left ventricular myocardium of dogs with chronic heart failure

Introduction: The signal transducer and activator of transcription 3 (STAT3) has been identified in mitochondria (MITO) of cardiomyocytes (mSTAT3). In STAT3 -/- cells, the activities of MITO complexes I and II of the electron transport chain (ETC) were reduced suggesting that mSTAT3 is required for optimal ETC function. Deactivation of STAT3, equated with dephosphorylation of tyrosine residues, has been shown to adversely impacted MITO respiration and, consequently, oxidative phosphorylation. We previously showed that long-term (3 months) therapy with elamipretide (ELAM, previously referred to as Bendavia TM, MTP131 or SS31), a novel MITO-targeting peptide, improves LV function and normalizes MITO respiration and rate of ATP synthesis in MITO of LV myocardium of dogs with heart failure (HF). Hypothesis: This study tested the hypothesis that phosphorylation of mSTAT3 (mpSTAT3) is reduced in MITO of LV myocardium of HF dogs and is restored after long-term therapy with ELAM. Methods: LV tissue was obtained from 14 dogs with microembolization-induced HF (LV ejection fraction ∼30%) randomized to 3 months therapy with subcutaneous injections of ELA (0.5 mg/kg once daily, n=7) or saline (Control, n=7). LV tissue from 6 normal (NL) dogs was used for comparison. Protein levels of mSTAT3 and mpSTAT3 were determined in MITO fraction by Western blotting coupled with chemiluminiscence and band intensity was quantified in densitometric units (du). Results: Protein level of mSTAT3 was 0.82±0.05 du in NL, decreased to 0.29±0.03 du in Controls (p Conclusions: mpSTAT3 level is reduced in MITO from LV of HF dogs and restored after chronic therapy with ELAM. Normalization of mpSTAT3 by ELAM likely contributed to be observed improvement in MITO function following therapy with ELAM in HF dogs

Reciprocal amplification of caspase-3 activity by nuclear export of a putative human RNA-modifying protein, PUS10 during TRAIL-induced apoptosis.

Pus10 is a pseudouridine synthase present in Archaea and Eukarya, but not in Bacteria and yeast. It has been suggested that the human PUS10 (DOBI) gene is needed during TRAIL-induced apoptosis. We analyzed the role of PUS10 in TRAIL-induced apoptosis by immunofluorescence, immunoblotting and several indicators of apoptosis. We examined several TRAIL-sensitive cell lines and we also examined some resistant cell lines after treatment with cycloheximide. PUS10 is mainly present in the nucleus. Early during apoptosis, PUS10 translocates to mitochondria via CRM1-mediated export with the concurrent release of cytochrome c and SMAC. Caspase-3 is required for PUS10 translocation, which reciprocally amplifies the activity of caspase-3 through the intrinsic/mitochondrial pathway. This suggests that in addition to cytoplasmic factors, nuclear factors also have a direct role in the major apoptosis pathways. However, p53 is not involved in TRAIL-induced PUS10 movement. The caspase-3-mediated movement of PUS10 and the release of mitochondrial contents enhancing caspase-3 activity creates a feedback amplification loop for caspase-3 action. Therefore, any defect in the movement or interactions of PUS10 would reduce the TRAIL sensitivity of tumor cells

Antibacterial Activity of Amchur (Dried Pulp of Unripe Mangifera indica) Extracts on Some Indigenous Oral Microbiota Causing Dental Caries

The antibacterial activity of amchur (dried pulp of unripe Mangifera indica) extract (50% ethanol) was tested against ten bacterial strains causing dental plaque by agar well diffusion method. The crude extract showed a broad spectrum of antibacterial activity inhibiting both the groups of Gram-positive & Gram-negative bacteria. The extract was most effective against Bacillus sp., followed by Staphylococcus mutans and Pseudomonas sp., whereas Halobacterium sp. was found to be the most resistant. Chlorhexidine (present in mouthwashes to prevent infection of dental caries) was used as a positive control. Natural extract of amchur was found to be more effective as compared to chlorhexidine. This study shows the potential of amchur in the treatment of dental caries

Effects of Elamipretide on Skeletal Muscle in Dogs with Experimentally Induced Heart Failure

AIMS: Elamipretide (ELAM), an aromatic-cationic tetrapeptide, interacts with cardiolipin and normalizes dysfunctional mitochondria of cardiomyocytes. This study examined the effects of ELAM on skeletal muscle mitochondria function in dogs with chronic heart failure (HF). METHODS AND RESULTS: Studies were performed in skeletal muscle biopsy specimens obtained from normal dogs (n = 7) and dogs with chronic intracoronary microembolization-induced HF (n = 14) treated with subcutaneous ELAM 0.5 mg/kg (HF + ELAM, n = 7) or vehicle (normal saline control, HF-CON, n = 7). After 3 months of therapy, triceps skeletal muscle samples were obtained from all dogs, and the proportion of type 1 and type 2 fibres was assessed. Mitochondria isolated from myofibrils of the vastus lateralis skeletal muscle exposed in vitro to ELAM for 1 h were used to assess mitochondrial function. The proportion of skeletal muscle type 1 fibres was lower in HF-CON dogs compared with normal dogs (23 ± 4 vs. 32 ± 5%, P \u3c 0.05). Treatment with ELAM restored a near-normal fibre-type composition (31 ± 7%, P \u3c 0.05 vs. HF-CON). Skeletal muscle mitochondria showed significantly lower levels of adenosine diphosphate-dependent mitochondrial respiration (100 ± 9 vs. 164 ± 15 natom O/min/mg protein, P \u3c 0.05), mitochondrial membrane potential (0.17 ± 0.03 vs. 0.53 ± 0.03 red/green fluorescence ratio, P \u3c 0.05), mitochondrial permeability transition pore (38 ± 3 vs. 62 ± 2 relative light units, P \u3c 0.05), maximum rate of adenosine triphosphate synthesis (3284 ± 418 vs. 8835 ± 423 RLU/μg protein, P \u3c 0.05), and cytochrome c oxidase activity (1390 ± 108 vs. 2459 ± 210 natom O/min/mg protein, P \u3c 0.05) compared with normal dogs. Exposure of skeletal muscle myofibrillar mitochondria from HF dogs to ELAM showed a dose-dependent improvement/normalization of all measures of mitochondrial function. In mitochondria from skeletal muscle of HF dogs exposed to 0.10 μM ELAM, adenosine diphosphate-dependent mitochondrial respiration increased to 183 ± 18 natom O/min/mg protein, membrane potential increased to 0.30 ± 0.03 red/green fluorescence ratio, mitochondrial permeability transition pore increased to 54 ± 4 RLU, maximum rate of adenosine triphosphate synthesis increased to 4423 ± 414, and cytochrome c oxidase activity increased to 2033 ± 191 natom O/min/mg protein. Exposure of skeletal muscle myofibrillar mitochondria from normal dogs to ELAM had no effect on mitochondrial function parameters. CONCLUSIONS: The results indicate that ELAM, previously shown to positively influence mitochondrial function of the failing heart, can also positively impact mitochondrial function of skeletal muscle and potentially help restore skeletal muscle function and improve exercise tolerance

Ancient Leishmania coronin (CRN12) is involved in microtubule remodeling during cytokinesis

In general, coronins play an important role in actin-based processes, and are expressed in a variety of eukaryotic cells, including Leishmania. Here, we show that Leishmania coronin preferentially distributes to the distal tip during cytokinesis, and interacts with microtubules through a microtubule-based motor, kinesin K39. We further show that reduction in coronin levels by 40-50% in heterozygous coronin mutants results in generation of bipolar cells (25-30%), specifically in the log phase, owing to unregulated growth of the corset microtubules. Further analysis of bipolar cells revealed that the main cause of generation of bipolar cell morphology is the intrusion of the persistently growing corset microtubules into the other daughter cell corset from the opposite direction. This defect in cytokinesis, however, disappears upon episomal gene complementation. Additionally, our attempts to prepare homozygous mutants were unsuccessful, as only the aneuploid cells survive the selection process. These results indicate that coronin regulates microtubule remodeling during Leishmania cytokinesis and is essentially required for survival of these parasites in culture