A lot-sizing problem in deliberated and controlled co-production systems

We consider an uncapacitated lot sizing problem in co-production systems, in which it is possible to produce multiple items simultaneously in a single production run. Each product has a deterministic demand to be satisfied on time. The decision is to choose which items to co-produce and the amount of production throughout a predetermined planning horizon. We show that the lot sizing problem with co-production is strongly NP-Hard. Then, we develop various mixed-integer linear programming (MILP) formulation of the problem and show that LP relaxations of all MILPs are equal. We develop a separation algorithm based on a set of valid inequalities, lower bounds based on a dynamic lot-sizing relaxation of our problem and a constructive heuristic that is used to obtain an initial solution for the solver, which form the basis of our proposed Branch & Cut algorithm for the problem. We test our models and algorithms on different data sets and provide the results.WOS:000754103800001Scopus - Affiliation ID: 60105072Science Citation Index ExpandedQ2-Q3Article; Early AccessUluslararası işbirliği ile yapılan - HAYIRŞubat2022YÖK - 2021-22Aralı

Image as a narrative in architecture

Günümüz görsel kültür ortamında indirgemeci bir yaklaşımla tek katmanlı olarak ele alınan imge kavramının zihinsel soyutlama yeteneğini zayıflattığı, düşünsel üretimin araçsallaştırılmasına neden olduğu düşünülmektedir. Bu bağlamda, mimarlıkta eleştirel düşünceyi tetikleyen imge kavramına farklı disiplinlerin penceresinden bakmak, farklı kavramlarla onu yeniden anlamlandırmak gerekmektedir. Bu çalışmada, nesnel biçimden zihinsel kurgu temsiline uzanan geniş bir yelpazede anlamlandırılan imge sorunsalı, eleştirel bir bakış açısıyla irdelenmekte ve mimarlıkta ilişkisel bilginin üretimine yol açabilecek bir okuma yöntemi önerilmektedir. Gündelik dilde görüntü ve biçim yerine kullanılan imgenin, biçime indirgenen yüzeysel algılama ve düşünme süreçlerine karşın imgeyi bir “anlatı olarak okuma”nın mimarlık bilgisinin üretimi için alternatif bir yaklaşım olabileceği tartışılmaktadır. Anlatı, zamansal deneyimin özelliklerini gösterdiği ölçüde yapılı çevrenin olay örgüsüne gönderme yapar. Anlatı olarak imge, bütüncül bir bakış açısı ile elde edilen mimarlık bilgisine ait “büyük resmi” bir olay örgüsüne dönüştürür. Herhangi bir yapılı çevreye ait imgenin katmanlı yapısı ve bu katmanlar arası ilişkileri bir olay örgüsüne dönüştürme sürecinde anlama, doğrusal düşünme biçimi yerine ağ ilişkisi ile temsil edilen karmaşık bir düşünme biçimini zorunlu kılar. Bu çalışmada imgeyi bir anlatı olarak okuma yöntemi, ilişkisel bilgiye ulaşmada bir örneklem olarak Kayseri Sahabiye Mahallesi imgesi üzerinden önerilmektedir. Tikel bir durum olan Sahabiye Mahallesi örneklemini genellenebilir kuramsal bilgi ile ilişkilendirerek deneyimleme; diğer bir deyişle, yapılı çevrenin katmanlı imge okumasını - tikel ve genel arasında gidip gelme hareketiyle eklenerek çoğalan ilişkisel bilgiye dönüştürme stratejisi, tezin kendine özgü yöntemini açıklamaktadır. Anahtar Kelimeler: Görsel kültür, imge, eleştiri, ilişkisel bilgi, anlatı / olay örgüsü. This study, proposes a method for the use of the "image" in architectural criticism, which is perceived as problematic of being a single layered, reductionist concept and dominating the mental processes figuratively. In everyday language, it is being used to define a wide spectrum of meanings from figural to the mental and expresses the thought, representation and criticism. For this reason, to redefine the concept of image as a narrative became necessary, in the field of architecture. In this study, it is argued that, reading the image as a narrative will recover the concept being shallow and reductionist, as it is understood extensively. It is thought that, reading the image as a narrative can be used as a key concept to generate the architectural knowledge from the built environment. In this context, it is thought that understanding and interpreting the "big picture" of architecture can be presented according to the holistic approach. Consequently, the image is presented with its multi-layered properties and the relations between these layers are important in understanding the meaning of the concept, which emerges within the network relations. This relationship requires both a mental process that will include the subject's background and priorities and the affordances of the environment. The narrative of the image is therefore thought to be emerged as the interactive relationship of the object and the subject. It is thought that, the cities, as living spaces having cultural codes, cannot be understood only by syntactic and analytic methods. Togetherness of the subject and the object is needed in order to solve the puzzle like structures of these environments. In such an understanding, the researcher has to experience the research area using her intentionality and try to find out the relations hidden among the layers of the environment. These relations can be considered as "a fold", as a Deleuzian concept, which allows all the layers reflect each other, and make visible the other. The intentionality of the researcher caused by the synergy of these relations will produce a fertile ground for exploring new layers of meanings that cannot be seen only by looking at. Image, considered as a mental construct, represents the subjective thought and the knowledge of the phenomenon can include many meanings. In architectural criticism, it is important to recognize the word as a loaded concept, and not to prefer or stick one of the meanings. According to the holistic approach, none of them is more important than the other, and the whole is greater than the parts. Reading the image of Sahabiye District in Kayseri as a narrative has been considered as an exemplar in this study. It is difficult to explain how to read the image of Sahabiye District as a narrative because of its multi-layered and complex structure having too many cultural codes superimposed within old and new environments. To recognize the experiential, cultural, historical, textural and social contrasts in the district makes its image multi-layered while reading the image as a narrative. The inexhaustibility of contrast (Ross, 1994), proposes an unlimited energy resulting from the tension of the opposing but complementary concepts. This tension makes each of these concepts being visible simultaneously. Sustainability referring to both continuity and change which represents contrast is another concept facilitates reading the image of Sahabiye District. The researcher, as an old resident of the district has a sustainable experience in there. The first-person phenomenological research method (Seamon, 2003) is adapted in this research in order to understand the deep meaning of this experience. Multi layered character of the image of this district, besides the empathic devotion and the theoretical background of the researcher makes the image of the Sahabiye District an exemplar give rise to relational knowledge. In this research, it is emphasized that reading the image of a build environment as a narrative can be translated to a generalized and sustainable knowledge which is contextual and specific to this environment. Reading the image of Sahabiye District as a narrative therefore exemplifies the proposed method based on web of events which is open to critical knowledge. As an exemplar, narrating Sahabiye  District will give rise to an in-between reality concerning singularity and multiplicity and having a potential to move between a specific and general knowledge. As a result, reading the image as a narrative in architectural environments introduces some possibilities for translating the multi-layered structures of the cityscape to critical knowledge that can be used for preservation and gentrification projects. Keywords: visual culture, image, architectural criticism, relational knowledge, narrative / web of event

Promoter DNA Methylation of Oncostatin M receptor-β as a Novel Diagnostic and Therapeutic Marker in Colon Cancer

In addition to genetic changes, the occurrence of epigenetic alterations is associated with accumulation of both genetic and epigenetic events that promote the development and progression of human cancer. Previously, we reported a set of candidate genes that comprise part of the emerging “cancer methylome”. In the present study, we first tested 23 candidate genes for promoter methylation in a small number of primary colon tumor tissues and controls. Based on these results, we then examined the methylation frequency of Oncostatin M receptor-β (OSMR) in a larger number of tissue and stool DNA samples collected from colon cancer patients and controls. We found that OSMR was frequently methylated in primary colon cancer tissues (80%, 80/100), but not in normal tissues (4%, 4/100). Methylation of OSMR was also detected in stool DNA from colorectal cancer patients (38%, 26/69) (cut-off in TaqMan-MSP, 4). Detection of other methylated markers in stool DNA improved sensitivity with little effect on specificity. Promoter methylation mediated silencing of OSMR in cell lines, and CRC cells with low OSMR expression were resistant to growth inhibition by Oncostatin M. Our data provide a biologic rationale for silencing of OSMR in colon cancer progression and highlight a new therapeutic target in this disease. Moreover, detection and quantification of OSMR promoter methylation in fecal DNA is a highly specific diagnostic biomarker for CRC

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy‐genetic liability measures suggest gene‐environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS‐SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene‐environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS‐SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early‐life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS‐SCZ at 75% with alternative cut‐points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EU-GEI)

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe