Private warehouse investment strategies in small versus large manufacturing firms

The research reported in this manuscript empirically compares the private warehouse investment strategies of small and large manufacturing firms. Mail surveys were administered to independent samples of small and large United States manufacturing firms. This research is based on a series of identically worded questions administered to both samples. Data was factor analyzed and cluster analyzed to identify three private warehouse investment strategies for small and large firms and two strategies for large firms. Analyses of three independent variables further evaluated differences in private warehouse investment strategies. Finally, the warehouse mix of small and of large firms was compared. This study identified specific private warehouse investment strategies, and warehouse mixes, in small and large United States manufacturing firms. Small firms were found to be less likely to use formal capital budgeting techniques and were less likely to consider strategic issues than large firms. Small firms were also found to be more likely to use private warehousing than large firms. This research increases the awareness of differences in logistics practice between small and large manufacturing firms and suggests that generalizations regarding logistics strategy should be approached with caution

A study of logistics strategies in small versus large U.S. manufacturing firms

The research reported in this manuscript empirically compares the similarities and differences of logistics strategies for small and large manufacturing firms. The hypotheses focus on whether there are significant differences between logistics strategies of small and large manufacturing firms and whether logistics strategy outcomes differ. The findings indicate that there are many similarities but differences do exist. The results identify dimensions of logistics strategy and assess their impact on logistics coordination effectiveness, customer service commitment, and company/division competitive responsiveness

A longitudial study of private warehouse investment strategies

This article revisits private warehouse investment decision making, a topic previously examined in 1989 by McGinnis, Kohn, and Myers (1990). Since then there has been a substantial amount of discussion regarding the scope and nature of logistics /supply chain management. In particular the roles of private, contract, and public warehousing has been discussed, increased emphasis on financial performance and strategic decision making may have altered the criteria for investment decisions in private warehousing, increased coordination of supply chains may have altered the relative importance of private, contract, and private warehousing, and increasing emphasis on controlling inventory investment may have shifted inventory responsibilities onto suppliers and customers. Empirical data was collected in 1999and 2008 regarding warehouse investment decisions in large United State manufacturing firms. This research focused on private warehouse investment decisions, topics that might affect those decisions, and the mix of private, contract, public, and other warehouse options. The results of the 1999 and 2008 data were compared to the earlier findings reported by McGinnis, Kohn, and Myers. Changes in private warehouse investment strategies, the roles of market /product mix uncertainties and availability of for-hire warehouse providers, and changes in warehouse mix were examined. Implications for practitioners, teachers, and researchers of transportation, supply chain management, logistics, and warehousing are discussed

Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: Clinical and molecular characterization

Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. LT response was defined as response to olaparib/placebo > 2 years, ST as < 3 months. Molecular analyses included germline BRCA1/2 status, three-biomarker homologous recombination deficiency (HRD) score, BRCA1 methylation, and mutational profiling. Another olaparib maintenance study (Study 41; NCT01081951) was used as an additional cohort. Results: Thirty-seven LT (32 olaparib) and 61 ST (21 olaparib) patients were identified. Treatment was significantly associated with outcome (P < 0.0001), with more LT patients on olaparib (60.4%) than placebo (11.1%). LT sensitivity to olaparib correlated with complete response to chemotherapy (P < 0.05). In the olaparib LT group, 244 genetic alterations were detected, with TP53, BRCA1, and BRCA2 mutations being most common (90%, 25%, and 35%, respectively). BRCA2 mutations were enriched among the LT responders. BRCA methylation was not associated with response duration. High myriad HRD score (>42) and/or BRCA1/2 mutation was associated with LT response to olaparib. Study 41 confirmed the correlation of LT response with olaparib and BRCA1/2 mutation. Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. (C) 2017 AACR

Distributed Fading Memory for Stimulus Properties in the Primary Visual Cortex

The brain has a one-back memory for visual stimuli. Neural responses to an image contain as much information about the current image as it does about another image presented immediately before

A Catalog of Neutral and Deleterious Polymorphism in Yeast

The abundance and identity of functional variation segregating in natural populations is paramount to dissecting the molecular basis of quantitative traits as well as human genetic diseases. Genome sequencing of multiple organisms of the same species provides an efficient means of cataloging rearrangements, insertion, or deletion polymorphisms (InDels) and single-nucleotide polymorphisms (SNPs). While inbreeding depression and heterosis imply that a substantial amount of polymorphism is deleterious, distinguishing deleterious from neutral polymorphism remains a significant challenge. To identify deleterious and neutral DNA sequence variation within Saccharomyces cerevisiae, we sequenced the genome of a vineyard and oak tree strain and compared them to a reference genome. Among these three strains, 6% of the genome is variable, mostly attributable to variation in genome content that results from large InDels. Out of the 88,000 polymorphisms identified, 93% are SNPs and a small but significant fraction can be attributed to recent interspecific introgression and ectopic gene conversion. In comparison to the reference genome, there is substantial evidence for functional variation in gene content and structure that results from large InDels, frame-shifts, and polymorphic start and stop codons. Comparison of polymorphism to divergence reveals scant evidence for positive selection but an abundance of evidence for deleterious SNPs. We estimate that 12% of coding and 7% of noncoding SNPs are deleterious. Based on divergence among 11 yeast species, we identified 1,666 nonsynonymous SNPs that disrupt conserved amino acids and 1,863 noncoding SNPs that disrupt conserved noncoding motifs. The deleterious coding SNPs include those known to affect quantitative traits, and a subset of the deleterious noncoding SNPs occurs in the promoters of genes that show allele-specific expression, implying that some cis-regulatory SNPs are deleterious. Our results show that the genome sequences of both closely and distantly related species provide a means of identifying deleterious polymorphisms that disrupt functionally conserved coding and noncoding sequences

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases