Information and Inventory Recourse for a Two-Market, Price-Setting Retailer

We analyze the problem of determining inventory and pricing decisions in a two-period retail setting when an opportunity to refine information about uncertain demand is available. The model extends the newsvendor problem with pricing by allowing for multiple suppliers, the pooling of procurement resources, and more general informational dynamics. One contribution is the solution procedure: we show that all decisions (up to seven in all, including recourse decisions) can be determined uniquely as a function of a surrogate first-period decision called the stocking factor. Hence, the two-period decision problem with recourse reduces to a search for one .decision variable. A second contribution is the policy implications: we find that the cost of learning is (I) a consequence of censored information because, on the margin, learning is free if full information is guaranteed; (2) measured in the form of an increased stocking factor; and (3) shared with the consumer in. the form of a higher selling price when demand uncertainty is additive. A third contribution is the application of the results to three motivating examples: A market research problem in which a product is introduced in a test market prior to a widespread launch; a global newsvendor problem in which a seasonal product is sold in two different countries with non-overlapping selling seasons; and a minimum-quantity commitment problem in which procurement resources for multiple purchases may be pooled

Delivering integrated child development care in Pakistan: protocol for a clustered randomised trial

Background: Early childhood developmental delay is associated with significant disadvantage in adult life. In Pakistan, high prevalence of developmental delay is associated with poverty, under-nutrition, and maternal depression. Aim: To assess the effectiveness of an early child development counselling intervention delivered at private GP clinics, in poor urban communities. Design & setting: A clustered randomised trial in Pakistan. Method: The intervention was developed following a period of formative research, and in consultation with local experts. A total of 2112 mother–child pairs will be recruited at 32 clinics, from within the locality (cluster); 16 clinics per arm. A primary care counselling intervention (promoting child development, nutrition, and maternal mental health) will be delivered at 6 weeks, 3, 6, and 9 months of the child’s age. Monitoring, assessment, and treatment will also be performed at quarterly visits in intervention clinics. Primary outcome is the developmental delay at 12 months (ASQ-3 scores). Secondary outcomes are stunting rate, and maternal depression (PHQ-9 score). In addition, a process evaluation and costing study will be conducted. Discussion: This trial will be the first to assess an early child development intervention, delivered in private GP clinics for poor urban communities in Pakistan. If found to be effective, this public–private model may offer a more sustainable, and feasible option for populations in poor urban settings, where private GP clinics are the most accessible provider of primary health care. There is scope for scale-up at provincial level, should the intervention be effective. Trial registration: The trial has been registered with the Current Controlled Trials ISRCTN48032200

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration

Due to the threat posed by the rapid growth in the resistance of microbial species to antibiotics, there is an urgent need to develop novel materials for biomedical applications capable of providing antibacterial properties without the use of such drugs. Bone healing represents one of the applications with the highest risk of postoperative infections, with potential serious complications in case of bacterial contaminations. Therefore, tissue engineering approaches aiming at the regeneration of bone tissue should be based on the use of materials possessing antibacterial properties alongside with biological and functional characteristics. In this study, we investigated the combination of polyhydroxyalkanoates (PHAs) with a novel antimicrobial hydroxyapatite (HA) containing selenium and strontium. Strontium was chosen for its well-known osteoinductive properties, while selenium is an emerging element investigated for its multi-functional activity as an antimicrobial and anticancer agent. Successful incorporation of such ions in the HA structure was obtained. Antibacterial activity against Staphylococcus aureus 6538P and Escherichia coli 8739 was confirmed for co-substituted HA in the powder form. Polymer-matrix composites based on two types of PHAs, P(3HB) and P(3HO-co-3HD-co-3HDD), were prepared by the incorporation of the developed antibacterial HA. An in-depth characterization of the composite materials was conducted to evaluate the effect of the filler on the physicochemical, thermal, and mechanical properties of the films. In vitro antibacterial testing showed that the composite samples induce a high reduction of the number of S. aureus 6538P and E. coli 8739 bacterial cells cultured on the surface of the materials. The films are also capable of releasing active ions which inhibited the growth of both Gram-positive and Gram-negative bacteria

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration

Due to the threat posed by the rapid growth in the resistance of microbial species to antibiotics, there is an urgent need to develop novel materials for biomedical applications capable of providing antibacterial properties without the use of such drugs. Bone healing represents one of the applications with the highest risk of postoperative infections, with potential serious complications in case of bacterial contaminations. Therefore, tissue engineering approaches aiming at the regeneration of bone tissue should be based on the use of materials possessing antibacterial properties alongside with biological and functional characteristics. In this study, we investigated the combination of polyhydroxyalkanoates (PHAs) with a novel antimicrobial hydroxyapatite (HA) containing selenium and strontium. Strontium was chosen for its well-known osteoinductive properties, while selenium is an emerging element investigated for its multi-functional activity as an antimicrobial and anticancer agent. Successful incorporation of such ions in the HA structure was obtained. Antibacterial activity against Staphylococcus aureus 6538P and Escherichia coli 8739 was confirmed for co-substituted HA in the powder form. Polymer-matrix composites based on two types of PHAs, P(3HB) and P(3HO-co-3HD-co-3HDD), were prepared by the incorporation of the developed antibacterial HA. An in-depth characterization of the composite materials was conducted to evaluate the effect of the filler on the physicochemical, thermal, and mechanical properties of the films. In vitro antibacterial testing showed that the composite samples induce a high reduction of the number of S. aureus 6538P and E. coli 8739 bacterial cells cultured on the surface of the materials. The films are also capable of releasing active ions which inhibited the growth of both Gram-positive and Gram-negative bacteria

Cross-talk between NFkB and the PI3-Kinase/AKT pathway can be targeted in primary effusion lymphoma (PEL) cell lines for efficient apoptosis

Background: A number of constitutively activated signaling pathways play critical roles in the survival and growth of primary effusion lymphoma cells (PELs) including NFkB and PI3/AKT kinase cascades. NFkBis constitutively activated in a number of malignancies, including multiple myeloma, Burkitt’s lymphoma and diffuse large cell B-cell lymphoma. However, its role in primary effusion lymphoma has not been fully explored. Methodology/Principal Findings: We used pharmacological inhibition and gene silencing to define the role of NFkB in growth and survival of PEL cells. Inhibition of NFkB activity by Bay11-7085 resulted in decreased expression of p65 in the nuclear compartment as detected by EMSA assays. In addition, Bay11-7085 treatment caused de-phosphorylation of AKT and its downstream targets suggesting a cross-talk between NFkB and the PI3-kinase/AKT pathway. Importantly, treatment of PEL cells with Bay11-7085 led to inhibition of cell viability and induced apoptosis in a dose dependent manner. Similar apoptotic effects were found when p65 was knocked down using specific small interference RNA. Finally, co-treatment of PEL cells with suboptimal doses of Bay11-7085 and LY294002 led to synergistic apoptotic responses in PEL cells.Conclusion/Significance: These data support a strong biological-link between NFkB and the PI3-kinase/AKT pathway in the modulation of anti-apoptotic effects in PEL cells. Synergistic targeting of these pathways using NFKB- and PI3-kinase/AKT- inhibitors may have a therapeutic potential for the treatment of PEL and possibly other malignancies with constitutive activation of these pathway

Dynamic localization of a helper NLR at the plant-pathogen interface underpins pathogen recognition

Plants employ sensor-helper pairs of NLR immune receptors to recognize pathogen effectors and activate immune responses (1). Yet the subcellular localization of NLRs pre- and post-activation during pathogen infection remains poorly understood. Here we show that NRC4, from the ‘NRC’ solanaceous helper NLR family (1), undergoes dynamic changes in subcellular localization by shuttling to and from the plant-pathogen haustorium interface established during infection by the Irish potato famine pathogen Phytophthora infestans. Specifically, prior to activation, NRC4 accumulates at the extra-haustorial membrane (EHM), presumably to mediate response to perihaustorial effectors, that are recognized by NRC4- dependent sensor NLRs. However not all NLRs accumulate at the EHM, as the closely related helper NRC2, and the distantly related ZAR1, did not accumulate at the EHM. NRC4 required an intact N-terminal coiled coil domain to accumulate at the EHM, whereas the functionally conserved MADA motif implicated in cell death activation and membrane insertion was dispensable for this process. Strikingly, a constitutively autoactive NRC4 mutant did not accumulate at the EHM and showed punctate distribution that mainly associated with the plasma membrane, suggesting that post-activation, NRC4 may undergo a conformation switch to form clusters that do not preferentially associate with the EHM. When NRC4 is activated by a sensor NLR during infection however, NRC4 forms puncta mainly at the EHM and to a lesser extent at the plasma membrane. We conclude that following activation at the EHM, NRC4 may spread to other cellular membranes from its primary site of activation to trigger immune responses

Biochemical, Histopathological and Therapeutic Studies in Alloxan- and Streptozotocin-induced Diabetes Mellitus in Rabbits.

The present experimental study was designed to establish diabetes mellitus in New Zealand white rabbits using diabetogenic drugs so as to investigate/elucidate biochemical, histopathological and behavioural changes/complications. In one group of rabbits diabetes mellitus was induced by intraperitoneal administration of alloxan (@ 80 mg/kg b.w.) and the other group of rabbits was made diabetic using intravenous administration of streptozotocin (@ 65 mg/kg b.w.).Another group of rabbits was kept as control (normal healthy) which received normal saline. The establishment of diabetes mellitus in rabbits was confirmed by periodical elevated levels of fasting blood glucose, blood urea and serum creatinine. The subsequent effect of hyperglycemia on tissue morphology of diabetic rabbits was studied by processing of different organs viz., pancreas, kidneys, liver, lungs, heart, brain and gut of both diabetic and normal rabbits for histological/hiostopathological study using Haematoxylin and Eosin stain and modified Gomori’s staining technique.Digital copy of Thesis.University of Kashmir

Cervical Cancer Risk Factors among Female High School Students in Baguio city

Objective: To determine and correlate the prevalence of cervical cancer risk factor exposures such as smoking, sexual activity, use of condoms, contraceptives pills, and history of STIs according to age and high school year level in Baguio city high-school students, Philippines. Background: Cervical cancer is the second cause of cancer deaths among women in the Philippines and the second most frequent cancer in women ages 15-44 [1]. Methods: The risk stratification level of cervical cancer development was determined using a questionnaire adapted from Siteman Cancer Center and Barnes- Jewish Hospital and Washington University School of Medicine. A coding manual was created for each of the risk factors and the level stratification of the risk factors. The study size was computed with the use of Open Epi, Version 2, open source calculator—SSPropo, an internet based epidemiologic calculator. Results: 98.3% of the study group was classified to have much below average risk of developing cervical cancer. 1.2% of the study group was of below average risk and 0.5% of the study group was with above average risk of cervical cancer with significant relationship to age of first sexual contact and number of sexual partners. Conclusion: An increased risk of cervical cancer among these students were associated with early onset of sexual activity, increasing number of sexual partners and early parity

An Assortment of Evolutionary Computation Techniques (AECT) in gaming

© 2020, Springer-Verlag London Ltd., part of Springer Nature. Real-time strategy (RTS) games differ as they persist in varying scenarios and states. These games enable an integrated correspondence of non-player characters (NPCs) to appear as an autodidact in a dynamic environment, thereby resulting in a combined attack of NPCs on human-controlled character (HCC) with maximal damage. This research aims to empower NPCs with intelligent traits. Therefore, we instigate an assortment of ant colony optimization (ACO) with genetic algorithm (GA)-based approach to first-person shooter (FPS) game, i.e., Zombies Redemption (ZR). Eminent NPCs with best-fit genes are elected to spawn NPCs over generations and game levels as yielded by GA. Moreover, NPCs empower ACO to elect an optimal path with diverse incentives and less likelihood of getting shot. The proposed technique ZR is novel as it integrates ACO and GA in FPS games where NPC will use ACO to exploit and optimize its current strategy. GA will be used to share and explore strategy among NPCs. Moreover, it involves an elaboration of the mechanism of evolution through parameter utilization and updation over the generations. ZR is played by 450 players with varying levels having the evolving traits of NPCs and environmental constraints in order to accumulate experimental results. Results revealed improvement in NPCs performance as the game proceeds

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification