Multiple order-up-to policy for mitigating bullwhip effect in supply chain network

This paper proposes a multiple order-up-to policy based inventory replenishment scheme to mitigate the bullwhip effect in a multi-stage supply chain scenario, where various transportation modes are available between the supply chain (SC) participants. The proposed policy is similar to the fixed order-up-to policy approach where replenishment decision “how much to order” is made periodically on the basis of the predecided order-up-to inventory level. In the proposed policy, optimal multiple order-up-to levels are assigned to each SC participants, which provides decision making reference point for deciding the transportation related order quantity. Subsequently, a mathematical model is established to define optimal multiple order-up-to levels for each SC participants that aims to maximize overall profit from the SC network. In parallel, the model ensures the control over supply chain pipeline inventory, high satisfaction of customer demand and enables timely utilization of available transportation modes. Findings from the various numerical datasets including stochastic customer demand and lead times validate that—the proposed optimal multiple order-up-to policy based inventory replenishment scheme can be a viable alternative for mitigating the bullwhip effect and well-coordinated SC. Moreover, determining the multiple order-up-to levels is a NP hard combinatorial optimization problem. It is found that the implementation of new emerging optimization algorithm named bacterial foraging algorithm (BFA) has presented superior optimization performances. The robustness and applicability of the BFA algorithm are further validated statistically by employing the percentage heuristic gap and two-way ANOVA analysis

Paracrine cellular senescence exacerbates biliary injury and impairs regeneration

Senescence has been suggested as causing biliary cholangiopathies but how this is regulated is unclear. Here, the authors generate a mouse model of biliary senescence by deleting Mdm2 in bile ducts and show that inhibiting TGFβ limits senescence-dependent aggravation of cholangiopathies

Transcutaneous flow related variables measured in vivo: the effects of gender

BACKGOUND: The identification of potential sources of error is a crucial step for any new assessment technique. This is the case for transcutaneous variables, such as flow and arterial gases, which have been applied as functional indicators of various aspects of human health. Regarding gender, a particular subject-related determinant, it is often claimed that women present higher transcutaneous oxygen pressure (tcpO(2)) values than men. However, the statistical significance of this finding is still uncertain. METHODS: The haemodynamical-vascular response to a local reactive hyperaemia procedure (the tourniquet cuff manoeuvre) was studied in two previously selected group of volunteers (n = 16; 8 women and 8 men). The effect of gender was assessed under standardised experimental conditions, using the transcutaneous flow-related variables tcpO(2)-tcpCO(2) and Laser-doppler Flowmetry (LDF). RESULTS: Regarding tcpO(2), statistically significant differences between genders were not found, although higher values were consistently found for the gases in the female group. Regarding LDF, high statistically significant differences (p < 0.005) were found, with the men's group presenting the highest values and variability. Other derived parameters used to characterise the vascular response following the cuff-deflation (t-peak) were similar in both groups. CONCLUSIONS: The relative influence of gender was not clearly demonstrated using these experimental conditions. However the gender-related LDF differences suggest that further investigation should be done on this issue. Perhaps in the presence of certain pathological disparities involving peripheral vascular regulation, other relationships may be found between these variables

Hydrogen Peroxide Probes Directed to Different Cellular Compartments

Background: Controlled generation and removal of hydrogen peroxide play important roles in cellular redox homeostasis and signaling. We used a hydrogen peroxide biosensor HyPer, targeted to different compartments, to examine these processes in mammalian cells. Principal Findings: Reversible responses were observed to various redox perturbations and signaling events. HyPer expressed in HEK 293 cells was found to sense low micromolar levels of hydrogen peroxide. When targeted to various cellular compartments, HyPer occurred in the reduced state in the nucleus, cytosol, peroxisomes, mitochondrial intermembrane space and mitochondrial matrix, but low levels of the oxidized form of the biosensor were also observed in each of these compartments, consistent with a low peroxide tone in mammalian cells. In contrast, HyPer was mostly oxidized in the endoplasmic reticulum. Using this system, we characterized control of hydrogen peroxide in various cell systems, such as cells deficient in thioredoxin reductase, sulfhydryl oxidases or subjected to selenium deficiency. Generation of hydrogen peroxide could also be monitored in various compartments following signaling events. Conclusions: We found that HyPer can be used as a valuable tool to monitor hydrogen peroxide generated in different cellular compartments. The data also show that hydrogen peroxide generated in one compartment could translocate to other compartments. Our data provide information on compartmentalization, dynamics and homeostatic control of hydrogen peroxide in mammalian cells

Rugged Single Domain Antibody Detection Elements for Bacillus anthracis Spores and Vegetative Cells

Significant efforts to develop both laboratory and field-based detection assays for an array of potential biological threats started well before the anthrax attacks of 2001 and have continued with renewed urgency following. While numerous assays and methods have been explored that are suitable for laboratory utilization, detection in the field is often complicated by requirements for functionality in austere environments, where limited cold-chain facilities exist. In an effort to overcome these assay limitations for Bacillus anthracis, one of the most recognizable threats, a series of single domain antibodies (sdAbs) were isolated from a phage display library prepared from immunized llamas. Characterization of target specificity, affinity, and thermal stability was conducted for six sdAb families isolated from rounds of selection against the bacterial spore. The protein target for all six sdAb families was determined to be the S-layer protein EA1, which is present in both vegetative cells and bacterial spores. All of the sdAbs examined exhibited a high degree of specificity for the target bacterium and its spore, with affinities in the nanomolar range, and the ability to refold into functional antigen-binding molecules following several rounds of thermal denaturation and refolding. This research demonstrates the capabilities of these sdAbs and their potential for integration into current and developing assays and biosensors

Fossil fuels in a trillion tonne world.

The useful energy services and energy density value of fossil carbon fuels could be retained for longer timescales into the future if their combustion is balanced by CO2 recapture and storage. We assess the global balance between fossil carbon supply and the sufficiency (size) and capability (technology, security) of candidate carbon stores. A hierarchy of value for extraction-to-storage pairings is proposed, which is augmented by classification of CO2 containment as temporary (100,000 yr). Using temporary stores is inefficient and defers an intergenerational problem. Permanent storage capacity is adequate to technically match current fossil fuel reserves. However, rates of storage creation cannot balance current and expected rates of fossil fuel extraction and CO2 consequences. Extraction of conventional natural gas is uniquely holistic because it creates the capacity to re-inject an equivalent tonnage of carbon for storage into the same reservoir and can re-use gas-extraction infrastructure for storage. By contrast, balancing the extraction of coal, oil, biomass and unconventional fossil fuels requires the engineering and validation of additional carbon storage. Such storage is, so far, unproven in sufficiency

Use of complementary and alternative medicines by a sample of Turkish women for infertility enhancement: a descriptive study

<p>Abstract</p> <p>Background</p> <p>Infertility patients are a vulnerable group that often seeks a non-medical solution for their failure to conceive. World-wide, women use CAM for productive health, but only a limited number of studies report on CAM use to enhance fertility. Little is known about traditional and religious forms of therapies that are used in relation to conventional medicine in Turkey. We investigated the prevalence and types of complementary and alternative medicine (CAM) used by infertile Turkish women for fertility enhancement.</p> <p>Methods</p> <p>A face-to-face questionnaire inquiring demographic information and types of CAM used for fertility enhancement were completed by hundred infertility patients admitted to a primary care family planning centre in Van, Turkey between January and July 2009.</p> <p>Results</p> <p>The vast majority of infertile women had used CAM at least once for infertility. CAM use included religious interventions, herbal products and recommendations of traditional "hodja's" (faith healers). Of these women, 87.8% were abused in the last 12 months, 36.6% felt not being supported by her partner and 80.5% had never spoken with a physician about CAM.</p> <p>Conclusions</p> <p>Infertile Turkish women use complementary medicine frequently for fertility enhancement and are in need of information about CAM. Religious and traditional therapies are used as an adjunct to, rather than a substitute for, conventional medical therapy. Physicians need to approach fertility patients with sensitivity and should be able to council their patients about CAM accordingly.</p

Standardized and reproducible methodology for the comprehensive and systematic assessment of surgical resection margins during breast-conserving surgery for invasive breast cancer

<p>Abstract</p> <p>Background</p> <p>The primary goal of breast-conserving surgery (BCS) is to completely excise the tumor and achieve "adequate" or "negative" surgical resection margins while maintaining an acceptable level of postoperative cosmetic outcome. Nevertheless, precise determination of the adequacy of BCS has long been debated. In this regard, the aim of the current paper was to describe a standardized and reproducible methodology for comprehensive and systematic assessment of surgical resection margins during BCS.</p> <p>Methods</p> <p>Retrospective analysis of 204 BCS procedures performed for invasive breast cancer from August 2003 to June 2007, in which patients underwent a standard BCS resection and systematic sampling of nine standardized re-resection margins (superior, superior-medial, superior-lateral, medial, lateral, inferior, inferior-medial, inferior-lateral, and deep-posterior). Multiple variables (including patient, tumor, specimen, and follow-up variables) were evaluated.</p> <p>Results</p> <p>6.4% (13/204) of patients had positive BCS specimen margins (defined as tumor at inked edge of BCS specimen) and 4.4% (9/204) of patients had close margins (defined as tumor within 1 mm or less of inked edge but not at inked edge of BCS specimen). 11.8% (24/204) of patients had at least one re-resection margin containing additional disease, independent of the status of the BCS specimen margins. 7.1% (13/182) of patients with negative BCS specimen margins (defined as no tumor cells seen within 1 mm or less of inked edge of BCS specimen) had at least one re-resection margin containing additional disease. Thus, 54.2% (13/24) of patients with additional disease in a re-resection margin would not have been recognized by a standard BCS procedure alone (P < 0.001). The nine standardized resection margins represented only 26.8% of the volume of the BCS specimen and 32.6% of the surface area of the BCS specimen.</p> <p>Conclusion</p> <p>Our methodology accurately assesses the adequacy of surgical resection margins for determination of which individuals may need further resection to the affected breast in order to minimize the potential risk of local recurrence while attempting to limit the volume of additional breast tissue excised, as well as to determine which individuals are not realistically amendable to BCS and instead need a completion mastectomy to successfully remove multifocal disease.</p

Gravitational-wave research as an emerging field in the Max Planck Society. The long roots of GEO600 and of the Albert Einstein Institute

On the occasion of the 50th anniversary since the beginning of the search for gravitational waves at the Max Planck Society, and in coincidence with the 25th anniversary of the foundation of the Albert Einstein Institute, we explore the interplay between the renaissance of general relativity and the advent of relativistic astrophysics following the German early involvement in gravitational-wave research, to the point when gravitational-wave detection became established by the appearance of full-scale detectors and international collaborations. On the background of the spectacular astrophysical discoveries of the 1960s and the growing role of relativistic astrophysics, Ludwig Biermann and his collaborators at the Max Planck Institute for Astrophysics in Munich became deeply involved in research related to such new horizons. At the end of the 1960s, Joseph Weber's announcements claiming detection of gravitational waves sparked the decisive entry of this group into the field, in parallel with the appointment of the renowned relativist Juergen Ehlers. The Munich area group of Max Planck institutes provided the fertile ground for acquiring a leading position in the 1970s, facilitating the experimental transition from resonant bars towards laser interferometry and its innovation at increasingly large scales, eventually moving to a dedicated site in Hannover in the early 1990s. The Hannover group emphasized perfecting experimental systems at pilot scales, and never developed a full-sized detector, rather joining the LIGO Scientific Collaboration at the end of the century. In parallel, the Max Planck Institute for Gravitational Physics (Albert Einstein Institute) had been founded in Potsdam, and both sites, in Hannover and Potsdam, became a unified entity in the early 2000s and were central contributors to the first detection of gravitational waves in 2015.Comment: 94 pages. Enlarged version including new results from further archival research. A previous version appears as a chapter in the volume The Renaissance of General Relativity in Context, edited by A. Blum, R. Lalli and J. Renn (Boston: Birkhauser, 2020

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship