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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejor.2010.06.016 Byline: H. Sebastian Heese (a), Jayashankar M. Swaminathan (b) Keywords: Bayesian inventory management; Sales effort; Unobservable lost sales Abstract: A retailer needs to make decisions regarding how much to order and how much sales effort to exert in an environment with uncertain demand. One intrinsic complexity in a typical retail environment is caused by the fact that the retailer can obtain information about demand only based on sales, as demand itself is unobservable. Taking a Bayesian approach, show that in such a setting a retailer should stock more to increase the probability of an exact demand observation. In this article, we extend their work by allowing the retailer to control both the stocking quantity and sales effort, which can be used to affect demand. We show that their insights with respect to information stalking carry over to this setting. In addition, our model allows gaining a better understanding of optimal sales effort strategies. We find that demand management has a dual role in supporting information gathering: while at the beginning of a product life cycle it is optimal to support learning effects by sharply reducing sales effort, at later stages of the product life cycle an aggressive strategy of increased promotional activities can be used to harvest the information gathered in earlier periods. Author Affiliation: (a) Kelley School of Business, Indiana University, Bloomington, IN 47405, USA (b) Kenan-Flagler Business School, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3490, USA Article History: Received 1 October 2008; Accepted 12 June 2010

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejor.2007.11.041 Byline: Wei Huang (a), Jayashankar M. Swaminathan (a)(b) Keywords: Pricing; Channel; Demand; Bound Abstract: In this paper we study the optimal pricing strategies when a product is sold on two channels such as the Internet and a traditional channel. We assume a stylized deterministic demand model where the demand on a channel depends on prices, degree of substitution across channels and the overall market potential. We first study four prevalent pricing strategies which differ in the degree of autonomy for the Internet channel. For a monopoly, we provide theoretical bounds for these pricing strategies. We also analyze the duopoly case where an incumbent mixed retailer faces competition with a pure retailer and characterize price equilibria. Finally, through a computational study, we explore the behavior (price and profits) under different parameters and consumer preferences for the alternative channels. Author Affiliation: (a) Department of Operations Research, University of North Carolina, Chapel Hill, NC 27599, United States (b) The Kenan-Flagler Business School, University of North Carolina, Chapel Hill, NC 27599, United States Article History: Received 24 October 2006; Accepted 15 November 2007

Semiconductor manufacturers face the difficulty of knowing when to purchase new tools to ensure that their new products are made with the latest technology. These tools are customized and it is difficult to determine when the tools will be completed. This model provides an efficient tool purchasing plan that takes into account demand uncertainty.

Phaeohyphomycosis is a rare fungal infection primarily affecting immunocompromised individuals. Its clinical manifestations are diverse, and diagnosis can be challenging, particularly when lesions mimic other conditions. A 66-year-old male, with a history of irregular leprosy treatment and prolonged steroid use, presented with symptoms suggestive of a nerve abscess. On examination, cystic swellings were observed on the left thumb and leg. Histopathological examination and fine needle aspiration cytology (FNAC) revealed melanized hyphae, leading to a final diagnosis of phaeohyphomycosis. The patient was treated with oral itraconazole, leading to regression in lesion size. Leprosy patients on long-term steroids are especially susceptible. The pathogenicity of these fungi in immunocompetent people is believed to be due to melanin in their cell walls, which defends against host defenses. Diagnosis involves histopathological examinations, staining, and fungal culture. Treatment involves surgical excision and antifungal drugs. If untreated, it can lead to severe complications including fatal brain infections. This case highlights the unusual presentation of phaeohyphomycosis mimicking a nerve abscess in a leprosy patient. It underscores the importance of a high degree of clinical suspicion in diagnosing such rare infections, particularly in immunocompromised individuals. It also emphasizes the value of FNAC in reaching a definitive diagnosis. Prompt diagnosis and appropriate treatment are essential to prevent potentially serious outcomes. • A high suspicion is required, as this can mimic conditions, such as nerve abscesses, particularly in patients with leprosy. • Prolonged use of steroids and immunosuppressive conditions, like leprosy, can predispose patients to phaeohyphomycosis. • Further research into the pathogenic mechanisms of these fungi, especially in immunocompetent individuals is needed. • FNAC with special stains in aspirated material can be pivotal for diagnosis. • Treatment involves surgical excision for cutaneous and subcutaneous lesions and medical management using antifungal drugs. [ABSTRACT FROM AUTHOR]

Mitochondria are complex organelles with a highly regulated architecture across all levels of organization. The architecture of the inner mitochondrial membrane (IMM) provides a crucial platform for many mitochondrial functions while mitochondrial network architecture is crucial for coordinating these activities throughout the cell. This review summarizes the recent findings regarding the most important shaping factors that regulate IMM organization, how IMM architecture supports bioenergetic functions and how IMM morphology adapts to meet other physiological needs of the cell. This review also highlights recent work suggesting that the functional connectivity of mitochondrial networks can be achieved not just by matrix continuity but also by inter-mitochondrial contact sites, which generate conductive continuity within a matrix-discontinuous mitochondrial network. [ABSTRACT FROM AUTHOR]

Mitochondrial organization, dynamics, and interactions with other intracellular structures and organelles are crucial for proper cell physiology. In this review we will discuss recent work on the significance of mitochondrial organization in regulating the size and distribution of mitochondrial DNA nucleoids and emphasize the importance of a new role for actin in regulating mitochondrial dynamics. We will also highlight new and unexpected examples of how mitochondria are integrated with many aspects of cell behavior, including cell migration, cell division, and the proper functioning of specialized cells such as neurons and immune cells. Together, these recent studies demonstrate the importance of mitochondrial organization in generating cellular architecture and vice versa. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel ether-linked bis(heterocycle)s have been synthesized via [3+2]-cycloaddition reaction of nitrile oxide with allyl alcohol followed by intramolecular 1,3-diploar cycloaddition reaction of nitrile imine with carbonyl group. All the newly synthesized compounds were screened for their anti-inflammatory and analgesic activities. Among the list of compounds (7a–k) studied, 7d, 7g, 7j, and 7k exhibited excellent activity comparable to ibuprofen and aspirin at the similar dosages. [Copyright &y& Elsevier]

Abstract: Experimental results from near shore bottom standing OWC based wave energy plants in Japan and India have now been available for about a decade. Historically the weakest link in the conversion efficiency of OWC based wave energy plants built so far has been the bidirectional turbine. This is possibly because a single turbine has been required to deliver power when the plant is exposed to random incident wave excitation varying by a factor of 10. A new topology that uses twin unidirectional turbines (which features a high efficiency spanning a broad range) is proposed. Using the Indian Wave Energy plant as a case study, it is shown that the power output from such a module considerably exceeds existing optimal configurations including those based on a fixed guide vane impulse turbine, linked guide vane impulse turbine or a Well''s turbine. A wave to wire efficiency of the order of 50% over the incident range is shown to be feasible in a credible manner by showing the output at all stages of the conversion process. A frequency domain technique is used to compute the OWC efficiency and a time domain approach used for the power module with the turbine pressure being the pivotal variable. [Copyright &y& Elsevier]

We report a neonate with transposition of great arteries and intact ventricular septum who had a massive pulmonary hemorrhage soon after an arterial switch operation. An emergency cardiac catheterization revealed a large bronchial collateral artery from the descending aorta feeding the right lung. The hemorrhage was controlled by coil embolization of the collateral, and the patient recovered after prolonged intensive care. [ABSTRACT FROM AUTHOR]

Quercetin, one of the most abundant of plant flavonoids, has been studied with a great deal of attention over the last several decades mainly for its properties in inflammation and allergy. In this study, we are reporting for the first time the in vivo immunostimulatory activity of quercetin in ovalbumin immunized Balb/c mice. Administration of quercetin (50 mg/kg body weight) along with ovalbumin antigen showed increased ovalbumin specific serum IgG antibody titres in comparison to the control group (p < 0.05). Quercetin administration not only showed predominance of Th2 immune response by increasing the IgG1 antibody titres, but also increased the infiltration of CD11c + dendritic cells in the mouse peritoneum and also increased LPS activated IL-1β and nitric oxide (NO) production by peritoneal macrophages. Expression of Tbx21, GATA-3 and Oct-2 proteins also enhanced in splenocytes of quercetin administered mice. Quercetin also did not cause any hemolysis in human RBCs. Overall, our findings strongly demonstrate the novel in vivo immunostimulatory and adjuvant potentials of quercetin. [ABSTRACT FROM AUTHOR]

Abstract: The twin unidirectional turbine topology was recently proposed with the promise of very significant improvements in the energy capture in Oscillating Water Column (OWC) based wave energy plants. Here, we present the initial results of the experimental validation of the twin unidirectional impulse turbine topology. A scale model of the concept was built and tested using simulated bidirectional flow. The model consists of two 165 mm impulse turbines each individually coupled to 375 W grid connected induction machines. An oscillatory flow test rig was used to simulate bidirectional flow to test the model. The results of the experiments validate the concept of the twin turbine configuration. The proposed topology utilizes no moving parts and achieves more than 50% efficiency over a broad range of flow coefficients. A comparison with other competing turbines (viz, a twin Wells’ turbine, a linked guide vane impulse turbine and a fixed guide vane impulse turbine) is done, based on actual measurements in the Indian wave energy plant. The results from the experiments are scaled to evaluate the design features of a 50 GWh wave energy plant. [Copyright &y& Elsevier]

Because of the high prevalence of adenovirus (Ad) infections in humans, it is believed that pre-existing Ad-neutralizing antibodies (vector immunity) may negatively impact the immune response to vaccine antigens when delivered by human Ad (HAd) vectors. In order to evaluate whether bovine Ad subtype 3 (BAd3), a non-HAd vector, can effectively elude high levels of pre-existing vector immunity, naïve and HAd serotype 5 (HAd)-primed mice were immunized with BAd-H5HA [BAd3 vector expressing the hemagglutinin (HA) gene from H5N1 influenza virus]. Even in the presence of very high levels of HAd-specific neutralizing antibody, no significant reductions in HA-specific humoral and cell-mediated immune (CMI) responses were observed in HAd-primed mice immunized with BAd-H5HA. In naïve mice immunized with HAd-H5HA (HAd5 vector expressing H5N1 HA) and boosted with BAd-H5HA, the humoral responses elicited were significantly higher (P < 0.01) than with either HAd-H5HA or BAd-H5HA alone, while the CMI responses were comparable in the groups. This finding underlines the importance of a heterologous prime-boost approach for achieving an enhanced immune response. The immunization of naïve or HAd-primed mice with BAd-H5HA bestowed full protection from morbidity and mortality following a potentially lethal challenge with A/Hong Kong/483/97. These results demonstrate the importance of BAd vectors as an alternate or supplement to HAd vectors for influenza pandemic preparedness.Molecular Therapy (2008); 16 5 965–971 doi:10.1038/mt.2008.12 [ABSTRACT FROM AUTHOR]

We report the synthesis, biological evaluation, and X-ray structural studies of a series of SARS-CoV-2 Mpro inhibitors based upon the X-ray crystal structure of nirmatrelvir, an FDA approved drug that targets the main protease of SARS-CoV-2. The studies involved examination of various P4 moieties, P1 five- and six-membered lactam rings to improve potency. In particular, the six-membered P1 lactam ring analogs exhibited high SARS-CoV-2 Mpro inhibitory activity. Several compounds effectively blocked SARS-CoV-2 replication in VeroE6 cells. One of these compounds maintained good antiviral activity against variants of concern including Delta and Omicron variants. A high-resolution X-ray crystal structure of an inhibitor bound to SARS-CoV-2 Mpro was determined to gain insight into the ligand-binding properties in the Mpro active site. [Display omitted] • Design and synthesis of potent SARS-CoV-2 Mpro inhibitors are reported. • Inhibitors with a six-membered P1 lactam exhibited improved antiviral activity. • Inhibitors maintained potent antiviral activity against variants of concern. • An inhibitor exhibited improved antiviral profile in immunocytochemistry assays. • The X-ray crystal structure of SARS-CoV-2 Mpro inhibitor complex was determined. [ABSTRACT FROM AUTHOR]

Neural processing differences of emotional facial expressions, while common in autism spectrum disorder (ASD), may be related to co-occurring alexithymia and interoceptive processing differences rather than autism per se. Here, we investigate relationships between alexithymia, interoceptive awareness of emotions, and functional connectivity during observation of facial expressions in youth (aged 8–17) with ASD (n = 28) compared to typically developing peers (TD; n = 37). Behaviorally, we found no significant differences between ASD and TD groups in interoceptive awareness of emotions, though alexithymia severity was significantly higher in the ASD group. In the ASD group, increased alexithymia was significantly correlated with lower interoceptive sensation felt during emotion. Using psycho-physiological interaction (PPI) analysis, the ASD group showed higher functional connectivity between the left ventral anterior insula and the left lateral prefrontal cortex than the TD group when viewing facial expressions. Further, alexithymia was associated with reduced left anterior insula-right precuneus connectivity and reduced right dorsal anterior insula-left ventral anterior insula connectivity when viewing facial expressions. In the ASD group, the degree of interoceptive sensation felt during emotion was positively correlated with left ventral anterior insula-right IFG connectivity when viewing facial expressions. However, across all participants, neither alexithymia nor interoceptive awareness of emotions predicted connectivity between emotion-related brain regions when viewing emotional facial expressions. To summarize, we found that in ASD compared to TD: 1) there is stronger connectivity between the insula and lateral prefrontal cortex; and 2) differences in interhemispheric and within left hemisphere connectivity between the insula and other emotion-related brain regions are related to individual differences in interoceptive processing and alexithymia. These results highlight complex relationships between alexithymia, interoception, and brain processing in ASD. • Autistics show more functional connectivity between the left anterior insula and the left lateral prefrontal cortex when viewing facial expressions. • For autistics, alexithymia severity and interoceptive ability modulate interhemispheric functional connectivity. • Across participants, alexithymia and interoceptive ability do not predict task based functional connectivity between emotion-related brain regions. • This data calls attention to the complex relationship between autism, alexithymia, interoception, and brain connectivity. [ABSTRACT FROM AUTHOR]

Design Safety and immunogenicity of a recombinant 14 kDa, fatty acid-binding protein(FABP) from Schistosoma mansoni (rSm14) were evaluated through an open, non-placebo-controlled, dose-standardized trial, performed at a single research site. The vaccine was formulated with glucopyranosyl lipid A (GLA) adjuvant in an oil-in-water emulsion (SE) and investigated in 20 male volunteers from a non-endemic area for schistosomiasis in the state of Rio de Janeiro, Brazil. Fifty microgram rSm14 with 10 μg GLA-SE (rSm14/GLA-SE)/dose were given intramuscularly three times with 30-day intervals. Participants were assessed clinically, biochemically and immunologically for up to 120 days. Methods Participants were screened for inclusion by physical examination, haematology and blood chemistry; then followed to assess adverse events and immunogenicity. Sera were tested for IgG (total and isotypes) and IgE. T cell induction of cytokines IL-2, IL-5, IL-10, IFNγ and TNFα was assessed by Milliplex kit and flow cytometry. Results The investigational product showed high tolerability; some self-limited, mild adverse events were observed during and after vaccine administration. Significant increases in Sm14-specific total IgG, IgG1 and IgG3 were observed 30 days after the first vaccination with specific IgG2 and IgG4 after 60 days. An increase in IgE antibodies was not observed at any time point. The IgG response was augmented after the second dose and 88% of all vaccinated subjects had developed high anti-Sm14 IgG titres 90 days after the first injection. From day 60 and onwards, there was an increase in CD4 + T cells producing single cytokines, particularly TNFα and IL-2, with no significant increase of multi-functional TH1 cells. Conclusion Clinical trial data on tolerability and specific immune responses after vaccination of adult, male volunteers in a non-endemic area for schistosomiasis with rSm14/GLA-SE, support this product as a safe, strongly immunogenic vaccine against schistosomiasis paving the way for follow-up Phase 2 trials. Study registration ID: NCT01154049 at http://www.clinicaltrials.gov . [ABSTRACT FROM AUTHOR]