A single period inventory model for incorporating two-ordering opportunities under imprecise demand information

The ordering strategy for a single period inventory model is the key to achieve success in the competitive business environment. This article considers demand in a form of fuzzy number and discusses the SPIM in which the retailer has the opportunity to reorder once during the period. The entire period/season is divided into two slots and the reorder is to be made during the mid-season after the early-season demand has been observed. The objective is to find the expected optimal order quantity together with profit maximization. We illustrate the implementation of the proposed model using a numerical example and explain that the explicit consideration of this reordering opportunity could lead us to better results in terms of profitability

Ross syndrome: a case report

Ross syndrome is a rare partial dysautonomic syndrome of unknown aetiology, characterized by segmental hypo/ anhidrosis associated with Holmes-Adie syndrome (tonic pupil and hypo/areflexia). The hypohydrosis or anhydrosis is patchy initially, later it becomes segmental or diffuse. This is due to affection of postganglionic cholinergic parasympathetic and sympathetic fibers involvement. There are a very few cases (approximately 50) have been reported in the literature since its original description. Author report a 22 years old male with classical features of Ross syndrome

Van der Knaap disease

Van der Knaap disease is a rare form of leukodystrophy, phenotypically characterized by megalencephaly, early-onset ataxia, pyramidal features, cognitive impairment, with an autosomal recessive inheritence. MRI Brain shows T1 and FLAIR hypointense subcortical cysts in mostly temporal lobes and in fronto-parietal subcortical areas. Authors report a 20 yr. girl with typical features

Muscle injury and impaired function, and insulin resistance in Chromogranin A knockout mice

Chromogranin A (CgA) is widely expressed in endocrine and neuroendocrine tissues as well as in the central nervous system. We observed CgA expression (mRNA and protein) in the gastrocnemius (GAS) muscle and found that performance of CgA-deficient Chga-KO mice in treadmill exercise was impaired. Supplementation with CgA in Chga-KO mice restored exercise ability suggesting a novel role for endogenous CgA in skeletal muscle function. Chga-KO mice display (i) lack of exercise-induced stimulation of pAKT, pTBC1D1 and phospho-p38 kinase signaling, (ii) loss of GAS muscle mass, (iii) extensive formation of tubular aggregates (TA), (iv) disorganized cristae architecture in mitochondria, (v) increased expression of the inflammatory cytokines Tnfα, Il6 and Ifnɣ, and fibrosis. The impaired maximum running speed and endurance in the treadmill exercise in Chga-KO mice correlated with decreased glucose uptake and glycolysis, defects in glucose oxidation and decreased mitochondrial cytochrome C oxidase activity. The lack of adaptation to endurance training correlated with the lack of stimulation of p38MAPK that is known to mediate the response to tissue damage. Since CgA sorts proteins to the regulated secretory pathway, we speculate that lack of CgA could cause misfolding of membrane proteins inducing aggregation of sarcoplasmic reticulum (SR) membranes and formation of tubular aggregates that is observed in Chga-KO mice. In conclusion, CgA deficiency renders the muscle energy deficient, impairs performance in treadmill exercise and prevents regeneration after exercise-induced tissue damage

Catestatin induces glycogenesis by stimulating the phosphoinositide 3-kinase-AKT pathway

Aim: Defects in hepatic glycogen synthesis contribute to post-prandial hyperglycaemia in type 2 diabetic patients. Chromogranin A (CgA) peptide Catestatin (CST: hCgA 352-372) improves glucose tolerance in insulin-resistant mice. Here, we seek to determine whether CST induces hepatic glycogen synthesis. Methods: We determined liver glycogen, glucose-6-phosphate (G6P), uridine diphosphate glucose (UDPG) and glycogen synthase (GYS2) activities; plasma insulin, glucagon, noradrenaline and adrenaline levels in wild-type (WT) as well as in CST knockout (CST-KO) mice; glycogen synthesis and glycogenolysis in primary hepatocytes. We also analysed phosphorylation signals of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-dependent kinase-1 (PDK-1), GYS2, glycogen synthase kinase-3β (GSK-3β), AKT (a kinase in AKR mouse that produces Thymoma)/PKB (protein kinase B) and mammalian/mechanistic target of rapamycin (mTOR) by immunoblotting. Results: CST stimulated glycogen accumulation in fed and fasted liver and in primary hepatocytes. CST reduced plasma noradrenaline and adrenaline levels. CST also directly stimulated glycogenesis and inhibited noradrenaline and adrenaline-induced glycogenolysis in hepatocytes. In addition, CST elevated the levels of UDPG and increased GYS2 activity. CST-KO mice had decreased liver glycogen that was restored by treatment with CST, reinforcing the crucial role of CST in hepatic glycogenesis. CST improved insulin signals downstream of IR and IRS-1 by enhancing phospho-AKT signals through the stimulation of PDK-1 and mTORC2 (mTOR Complex 2, rapamycin-insensitive complex) activities. Conclusions: CST directly promotes the glycogenic pathway by (a) reducing glucose production, (b) increasing glycogen synthesis from UDPG, (c) reducing glycogenolysis and (d) enhancing downstream insulin signalling

An overview of airborne measurement in Nepal – Part 1: Vertical profile of aerosol size, number, spectral absorption, and meteorology

The paper provides an overview of an airborne measurement campaign with a microlight aircraft over the Pokhara Valley region, Nepal, a metropolitan region in the central Himalayan foothills. This is the first aerial measurement in the central Himalayan foothill region, one of the polluted but relatively poorly sampled regions of the world. Conducted in two phases (in May 2016 and December 2016–January 2017), the goal of the overall campaign was to quantify the vertical distribution of aerosols over a polluted mountain valley in the Himalayan foothills, as well as to investigate the extent of regional transport of emissions into the Himalayas. This paper summarizes results from the first phase where test flights were conducted in May 2016 (pre-monsoon), with the objective of demonstrating the potential of airborne measurements in the region using a portable instrument package (size with housing case: 0.45 m × 0.25 m × 0.25 m, 15 kg) onboard an ultralight aircraft (IKARUS-C42). A total of five sampling test flights were conducted (each lasting for 1–1.5 h) in the Pokhara Valley to characterize vertical profiles of aerosol properties such as aerosol number and size distribution (0.3–2 µm), total particle concentration (>14 nm), aerosol absorption (370–950 nm), black carbon (BC), and meteorological variables. Although some interesting observations were made during the test flight, the study is limited to a few days (and only a few hours of flight in total) and thus the analysis presented may not represent the entire pollution–meteorology interaction found in the Pokhara Valley. The vertical profiles of aerosol species showed decreasing concentrations with altitude (815 to 4500 m a.s.l.); a steep concentration gradient below 2000 m a.s.l. in the morning; and mixed profiles (up to ca. 4000 m a.s.l.) in the afternoon. The near-surface (<1000 m a.s.l.) BC concentrations observed in the Pokhara Valley were much lower than pre-monsoon BC concentrations in the Kathmandu Valley, and similar in range to Indo-Gangetic Plain (IGP) sites such as Kanpur in India. The sampling test flight also detected an elevated polluted aerosol layer (around 3000 m a.s.l.) over the Pokhara Valley, which could be associated with the regional transport. The total aerosol and black carbon concentration in the polluted layer was comparable with the near-surface values. The elevated polluted layer was also characterized by a high aerosol extinction coefficient (at 550 nm) and was identified as smoke and a polluted dust layer. The observed shift in the westerlies (at 20–30∘ N) entering Nepal during the test flight period could be an important factor for the presence of elevated polluted layers in the Pokhara Valle

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease

Anticancer property of Bryophyllum pinnata (Lam.) Oken. leaf on human cervical cancer cells

<p>Abstract</p> <p>Background</p> <p><it>Bryophyllum pinnata </it>(<it>B. pinnata</it>) is a common medicinal plant used in traditional medicine of India and of other countries for curing various infections, bowel diseases, healing wounds and other ailments. However, its anticancer properties are poorly defined. In view of broad spectrum therapeutic potential of <it>B. pinnata </it>we designed a study to examine anti-cancer and anti-Human Papillomavirus (HPV) activities in its leaf extracts and tried to isolate its active principle.</p> <p>Methods</p> <p>A chloroform extract derived from a bulk of botanically well-characterized pulverized <it>B</it>. <it>pinnata </it>leaves was separated using column chromatography with step- gradient of petroleum ether and ethyl acetate. Fractions were characterized for phyto-chemical compounds by TLC, HPTLC and NMR and Biological activity of the fractions were examined by MTT-based cell viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and assay of apoptosis related proteins by immunoblotting in human cervical cancer cells.</p> <p>Results</p> <p>Results showed presence of growth inhibitory activity in the crude leaf extracts with IC₅₀at 552 μg/ml which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50:50) and showed IC₅₀at 91 μg/ml. Investigations of anti-viral activity of the extract and its fraction revealed a specific anti-HPV activity on cervical cancer cells as evidenced by downregulation of constitutively active AP1 specific DNA binding activity and suppression of oncogenic c-Fos and c-Jun expression which was accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4 strongly induced apoptosis as evidenced by an increased expression of the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of fraction F4 by HPTLC and NMR indicated presence of activity that resembled Bryophyllin A.</p> <p>Conclusions</p> <p>Our study therefore demonstrates presence of anticancer and anti-HPV an activity in <it>B</it>. <it>pinnata </it>leaves that can be further exploited as a potential anticancer, anti-HPV therapeutic for treatment of HPV infection and cervical cancer.</p