63 research outputs found
Reducing Transport Miles Through the Use of Mobile Hubs: A Case Study in Local Food Supply Chains
Though environmentally friendly in many regards, local supply chains are often inefficient due to lack of proper infrastructure. This paper explores the use and placement of mobile hubs for consolidation and distribution of goods in local supply chains. Specifically, we look at local food supply chains where food typically travels from rural farms to suburban and urban restaurants. Currently, consolidation is minimal and not optimized in these supply chains. This paper computes suitability and location analysis through a novel multi-criterion scoring methodology utilizing kernel density and network analysis. The effectiveness of these mobile hubs is assessed through strategic routing, where the routes are optimized for time and distance. Results indicate that on average mobile hubs do in fact reduce mileage and number of stops, lessening emissions in addition to saving time and money. The proposed methodology can be implemented in other local supply chains to better consolidate and distribute goods
Hyperconnected Fresh Supply Chains: Logistics & Market Expansion Frameworks
This thesis contributes novel frameworks that utilize transdisciplinary approaches to Fresh Supply Chain and Logistics Problems via Operations Research, GIS and Strategic Management. These fresh supply chain frameworks help build market deployment roadmaps, hub location in local supply chains and sustainable logistics strategies. Our study helps to provide solution approaches that are directly implementable in Industry.Ph.D
Cosmic Bell Test: Measurement Settings from Milky Way Stars
Bell’s theorem states that some predictions of quantum mechanics cannot be reproduced by a local-realist theory. That conflict is expressed by Bell’s inequality, which is usually derived under the assumption that there are no statistical correlations between the choices of measurement settings and anything else that can causally affect the measurement outcomes. In previous experiments, this “freedom of choice” was addressed by ensuring that selection of measurement settings via conventional “quantum random number generators” was spacelike separated from the entangled particle creation. This, however, left open the possibility that an unknown cause affected both the setting choices and measurement outcomes as recently as mere microseconds before each experimental trial. Here we report on a new experimental test of Bell’s inequality that, for the first time, uses distant astronomical sources as “cosmic setting generators.” In our tests with polarization-entangled photons, measurement settings were chosen using real-time observations of Milky Way stars while simultaneously ensuring locality. Assuming fair sampling for all detected photons, and that each stellar photon’s color was set at emission, we observe statistically significant ≳7.31σ and ≳11.93σ violations of Bell’s inequality with estimated p values of ≲1.8×10[superscript -13] and ≲4.0×10[superscript -33], respectively, thereby pushing back by ∼600 years the most recent time by which any local-realist influences could have engineered the observed Bell violation.Austrian Academy of SciencesAustrian Science Fund (Projects SFB F40 (FOQUS) and CoQuS W1210-N16)Austria. Federal Ministry of Science, Research, and EconomyNational Science Foundation (U.S.) (INSPIRE Grant PHY-1541160 and SES-1056580)Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra
U-CAN-seq: A Universal Competition Assay by Nanopore Sequencing
RNA viruses quickly evolve subtle genotypic changes that can have major impacts on viral fitness and host range, with potential consequences for human health. It is therefore important to understand the evolutionary fitness of novel viral variants relative to well-studied genotypes of epidemic viruses. Competition assays are an effective and rigorous system with which to assess the relative fitness of viral genotypes. However, it is challenging to quickly and cheaply distinguish and quantify fitness differences between very similar viral genotypes. Here, we describe a protocol for using reverse transcription PCR in combination with commercial nanopore sequencing services to perform competition assays on untagged RNA viruses. Our assay, called the Universal Competition Assay by Nanopore Sequencing (U-CAN-seq), is relatively cheap and highly sensitive. We used a well-studied N24A mutation in the chikungunya virus (CHIKV) nsp3 gene to confirm that we could detect a competitive disadvantage using U-CAN-seq. We also used this approach to show that mutations to the CHIKV 5′ conserved sequence element that disrupt sequence but not structure did not affect the fitness of CHIKV. However, similar mutations to an adjacent CHIKV stem loop (SL3) did cause a fitness disadvantage compared to wild-type CHIKV, suggesting that structure-independent, primary sequence determinants in this loop play an important role in CHIKV biology. Our novel findings illustrate the utility of the U-CAN-seq competition assay
BAT AGN Spectroscopic Survey. XX. Molecular Gas in Nearby Hard-X-Ray-selected AGN Galaxies
We present the host-galaxy molecular gas properties of a sample of 213 nearby (0.01 10.5) tend to have more molecular gas and higher gas fractions than inactive galaxies matched in stellar mass. When matched in star formation, we find AGN galaxies show no difference from inactive galaxies, with no evidence that AGN feedback affects the molecular gas. The higher molecular gas content is related to AGN galaxies hosting a population of gas-rich early types with an order of magnitude more molecular gas and a smaller fraction of quenched, passive galaxies (~5% versus 49%) compared to inactive galaxies. The likelihood of a given galaxy hosting an AGN (L_(bol) > 10⁴⁴ erg s⁻¹ ) increases by ~10–100 between a molecular gas mass of 10^(8.7) M_⊙ and 10^(10.2) M_⊙. AGN galaxies with a higher Eddington ratio (log(L/L_(Edd)) > −1.3) tend to have higher molecular gas masses and gas fractions. The log(N_H/ cm⁻² ) > 23.4) of AGN galaxies with higher column densities are associated with lower depletion timescales and may prefer hosts with more gas centrally concentrated in the bulge that may be more prone to quenching than galaxy-wide molecular gas. The significant average link of host-galaxy molecular gas supply to supermassive black hole (SMBH) growth may naturally lead to the general correlations found between SMBHs and their host galaxies, such as the correlations between SMBH mass and bulge properties, and the redshift evolution of star formation and SMBH growth
Shared decision-making performance of general practice residents: an observational study combining observer, resident, and patient perspectives
Background: Shared decision making (SDM) is considered fundamental to person-centred care. However, applying SDM may be a challenge for residents in general practice, since it is a complex competence that requires the integration of knowledge and skills from several competency domains. Objective: To support learning of SDM during medical residency, we aimed to gain insight in Dutch residents’ observed and perceived SDM performance in general practice. Methods: We evaluated residents’ SDM performance from an observer, resident, and patient perspective. Consultations of first- and third-year residents were recorded. Trained observers used the validated Observing Patient Involvement (OPTION5) scale to assess observed SDM performance of residents in 98 actual recorded consultations. Perceived SDM performance was evaluated by residents and patients completing validated SDM questionnaires, supplemented with questions about (the context of) the consultation and perceived relevance of SDM immediately after the consultation. The data were analysed using descriptive statistics (mean, SD, minimums, and maximums) and explorative bivariate analyses. Results: The residents’ observed mean SDM performance was 19.1 (range, 0–100, SD = 10.9), mean resident self-reported SDM performance was 56.9 (range, 0–100, SD = 18.5), and mean patient-reported SDM performance was 73.3 (range, 0–100, SD = 26.8). We found a significant and positive correlation between observed SDM performance and residents’ perceived relevance of SDM for the consultation (t = 4.571, P ≤ 0.001) and the duration of the consultation (r = 0.390, P ≤ 0.001). Conclusions: This study showed that there is room for increasing awareness of the potential incongruence between observed and perceived SDM performance during medical residency, in order to facilitate the implementation of SDM in clinical practice
Atualizações sobre a cirurgia oncoplástica da mama: Updates on oncoplastic breast surgery
A cirurgia oncoplástica da mama mescla os princípios da cirurgia oncológica e reconstrutiva, com os objetivos de alcançar a sobrevida ideal, mantendo ou reconstruindo uma mama cosmeticamente aceitável, seja por meio de cirurgia conservadora da mama ou mastectomia. As técnicas de cirurgia oncoplástica da mama podem ser classificadas por complexidade crescente, a técnica básica pode ser facilmente aprendida e aperfeiçoada pela maioria dos cirurgiões de mama; o domínio de técnicas complexas geralmente requer treinamento adicional na área ou a assistência de um cirurgião plástico no momento da cirurgia oncológica. O objetivo dos procedimentos oncoplásticos é ressecar o câncer de mama com margens histológicas negativas, preservando o contorno da mama, a cirurgia oncoplástica combina os princípios da cirurgia oncológica e reconstrutiva, utilizando um espectro de técnicas de aprimoramento estético para tratar defeitos teciduais e otimizar a estética da cirurgia de câncer de mama. Além disso, tem a oportunidade de abordar os desejos de remodelação existentes do paciente. A técnica básica para lumpectomia é uma técnica única baseada em descolamento de plano duplo, ele pode ser usado para extirpar até 20 por cento do volume da mama. Os resultados oncológicos da cirurgia oncoplástica são comparáveis ou superiores aos da cirurgia conservadora da mama padrão, e as taxas de complicações relatadas são baixas. Assim, as opções oncoplásticas devem ser consideradas para cada paciente com câncer de mama
Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans
The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development
Genetic correlation between amyotrophic lateral sclerosis and schizophrenia
A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe
Synaptic interactome mining reveals p140Cap as a new hub for PSD proteins involved in psychiatric and neurological disorders
Altered synaptic function has been associated with neurological and psychiatric conditions including intellectual disability, schizophrenia and autism spectrum disorder (ASD). Amongst the recently discovered synaptic proteins is p140Cap, an adaptor that localizes at dendritic spines and regulates their maturation and physiology. We recently showed that p140Cap knockout mice have cognitive deficits, impaired long-term potentiation (LTP) and long-term depression (LTD), and immature, filopodia-like dendritic spines. Only a few p140Cap interacting proteins have been identified in the brain and the molecular complexes and pathways underlying p140Cap synaptic function are largely unknown. Here, we isolated and characterized the p140Cap synaptic interactome by co-immunoprecipitation from crude mouse synaptosomes, followed by mass spectrometry-based proteomics. We identified 351 p140Cap interactors and found that they cluster to sub complexes mostly located in the postsynaptic density (PSD). p140Cap interactors converge on key synaptic processes, including transmission across chemical synapses, actin cytoskeleton remodeling and cell-cell junction organization. Gene co-expression data further support convergent functions: the p140Cap interactors are tightly co-expressed with each other and with p140Cap. Importantly, the p140Cap interactome and its co-expression network show strong enrichment in genes associated with schizophrenia, autism, bipolar disorder, intellectual disability and epilepsy, supporting synaptic dysfunction as a shared biological feature in brain diseases. Overall, our data provide novel insights into the molecular organization of the synapse and indicate that p140Cap acts as a hub for postsynaptic complexes relevant to psychiatric and neurological disorders
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