A Framework for Multi-dimensional Assessment of the Impacts of Overweight Vehicle Operations and a Corridor-Level Case Study

Ground freight transportation is essential for the economy of any region. The efficient movement of goods from one location to another connects businesses with suppliers and customers, that enhances commerce and ultimately boosts the economy. The high volume of freight that has been transported on the nation’s highway network has allowed the trucking industry to provide enormous socio-economic benefits. Unfortunately, these benefits come with some costs associated with the operation of overweight (OW) trucks, such as accelerated deterioration of highway pavement and bridge assets, and passenger and freight traffic safety degradation. Thus, to manage safety risk, traffic mobility, and infrastructure deterioration on the highway network, state agencies have established weight restrictions and permit policies to regulate the operation of OW trucks in their jurisdictions. However, the task of finding a balance between an adequate recovery of highway asset repair expenditures and reasonable OW permitting policies that do not impair the propitious economic environment of trucking operations in the state is challenging. Consequently, to make informed decisions, highway agencies are in need of knowledge regarding the potential effects of changes in these policies in terms of infrastructure damage, revenues collection, traffic operation, and road user costs. To address the various costs and benefits associated with the operation of OW truck operations, this study proposed a multi-criteria decision analysis (MCDA) framework to enable prioritization of the wide range of criteria involved in changes in policies related to trucking operations. A major feature of this framework is its ability to allow the simultaneous consideration of different standpoints such as economic, public, and private sector that can assist agencies achieve more balance, rational, and defensible decisions. The proposed MCDA framework incorporates some of the most relevant performance criteria used in the evaluation of OW permitting policies including infrastructure damage, safety, traffic mobility, OW permitting revenues, vehicle operation costs for trucks and shipping inventory cost. Lastly, the proposed framework was applied to I-70, a highway corridor with some of the highest OW truck traffic in the state of Indiana, to demonstrate its implementation

Nod2 Suppresses Borrelia burgdorferi Mediated Murine Lyme Arthritis and Carditis through the Induction of Tolerance

The internalization of Borrelia burgdorferi, the causative agent of Lyme disease, by phagocytes is essential for an effective activation of the immune response to this pathogen. The intracellular, cytosolic receptor Nod2 has been shown to play varying roles in either enhancing or attenuating inflammation in response to different infectious agents. We examined the role of Nod2 in responses to B. burgdorferi. In vitro stimulation of Nod2 deficient bone marrow derived macrophages (BMDM) resulted in decreased induction of multiple cytokines, interferons and interferon regulated genes compared with wild-type cells. However, B. burgdorferi infection of Nod2 deficient mice resulted in increased rather than decreased arthritis and carditis compared to control mice. We explored multiple potential mechanisms for the paradoxical response in in vivo versus in vitro systems and found that prolonged stimulation with a Nod2 ligand, muramyl dipeptide (MDP), resulted in tolerance to stimulation by B. burgdorferi. This tolerance was lost with stimulation of Nod2 deficient cells that cannot respond to MDP. Cytokine patterns in the tolerance model closely paralleled cytokine profiles in infected Nod2 deficient mice. We propose a model where Nod2 has an enhancing role in activating inflammation in early infection, but moderates inflammation after prolonged exposure to the organism through induction of tolerance

Functional analysis of RNA structures present at the 3' extremity of the murine norovirus genome: the variable polypyrimidine tract plays a role in viral virulence.

Interactions of host cell factors with RNA sequences and structures in the genomes of positive-strand RNA viruses play various roles in the life cycles of these viruses. Our understanding of the functional RNA elements present in norovirus genomes to date has been limited largely to in vitro analysis. However, we recently used reverse genetics to identify evolutionarily conserved RNA structures and sequences required for norovirus replication. We have now undertaken a more detailed analysis of RNA structures present at the 3′ extremity of the murine norovirus (MNV) genome. Biochemical data indicate the presence of three stable stem-loops, including two in the untranslated region, and a single-stranded polypyrimidine tract [p(Y)] of variable length between MNV isolates, within the terminal stem-loop structure. The well-characterized host cell pyrimidine binding proteins PTB and PCBP bound the 3′-untranslated region via an interaction with this variable sequence. Viruses lacking the p(Y) tract were viable both in cell culture and upon mouse infection, demonstrating that this interaction was not essential for virus replication. However, competition analysis with wild-type MNV in cell culture indicated that the loss of the p(Y) tract was associated with a fitness cost. Furthermore, a p(Y)-deleted mutant showed a reduction in virulence in the STAT1−/− mouse model, highlighting the role of RNA structures in norovirus pathogenesis. This work highlights how, like with other positive-strand RNA viruses, RNA structures present at the termini of the norovirus genome play important roles in virus replication and virulence

The Relationship between Independent Transfer Skills and Upper Limb Kinetics in Wheelchair Users

Transfers are one of the most physically demanding wheelchair activities. The purpose of this study was to determine if using proper transfer skills as measured by the Transfer Assessment Instrument (TAI) is associated with reduced loading on the upper extremities. Twenty-three wheelchair users performed transfers to a level-height bench while a series of forces plates, load cells, and a motion capture system recorded the biomechanics of their natural transferring techniques. Their transfer skills were simultaneously evaluated by two study clinicians using the TAI. Logistic regression and multiple linear regression models were used to determine the relationships between TAI scores and the kinetic variables on both arms across all joints. The results showed that the TAI measured transfer skills were closely associated with the magnitude and timing of joint moments ( < .02, model R 2 values ranged from 0.27 to 0.79). Proper completion of the skills which targeted the trailing arm was associated with lower average resultant moments and rates of rise of resultant moments at the trailing shoulder and/or elbow. Some skills involving the leading side had the effect of increasing the magnitude or rate loading on the leading side. Knowledge of the kinetic outcomes associated with each skill may help users to achieve the best load-relieving effects for their upper extremities

Constructivism: Defense or a Continual Critical Appraisal – A Response to Gil-Pérez et al.

Abstract. This commentary is a critical appraisal of Gil-Pérez et al.’s (2002) conceptualization of constructivism. It is argued that the following aspects of their presentation are problematic: (a) Although the role of controversy is recognized, the authors implicitly subscribe to a Kuhnian perspective of ‘normal’ science; (b) Authors fail to recognize the importance of von Glasersfeld’s contribution to the understanding of constructivism in science education; (c) The fact that it is not possible to implement a constructivist pedagogy without a constructivist epistemology has been ignored; and (d) Failure to recognize that the metaphor of the ‘student as a developing scientist’ facilitates teaching strategies as students are confronted with alternative/rival/conflicting ideas. Finally, we have shown that constructivism in science education is going through a process of continual critical appraisals

Increased serum kallistatin levels in type 1 diabetes patients with vascular complications

BACKGROUND: Kallistatin, a serpin widely produced throughout the body, has vasodilatory, anti-angiogenic, anti-oxidant, and anti-inflammatory effects. Effects of diabetes and its vascular complications on serum kallistatin levels are unknown. METHODS: Serum kallistatin was quantified by ELISA in a cross-sectional study of 116 Type 1 diabetic patients (including 50 with and 66 without complications) and 29 non-diabetic controls, and related to clinical status and measures of oxidative stress and inflammation. RESULTS: Kallistatin levels (mean(SD)) were increased in diabetic vs. control subjects (12.6(4.2) vs. 10.3(2.8) μg/ml, p = 0.007), and differed between diabetic patients with complications (13.4(4.9) μg/ml), complication-free patients (12.1(3.7) μg/ml), and controls; ANOVA, p = 0.007. Levels were higher in diabetic patients with complications vs. controls, p = 0.01, but did not differ between complication-free diabetic patients and controls, p > 0.05. On univariate analyses, in diabetes, kallistatin correlated with renal dysfunction (cystatin C, r = 0.28, p = 0.004; urinary albumin/creatinine, r = 0.34, p = 0.001; serum creatinine, r = 0.23, p = 0.01; serum urea, r = 0.33, p = 0.001; GFR, r = -0.25, p = 0.009), total cholesterol (r = 0.28, p = 0.004); LDL-cholesterol (r = 0.21, p = 0.03); gamma-glutamyltransferase (GGT) (r = 0.27, p = 0.04), and small artery elasticity, r = -0.23, p = 0.02, but not with HbA1c, other lipids, oxidative stress or inflammation. In diabetes, geometric mean (95%CI) kallistatin levels adjusted for covariates, including renal dysfunction, were higher in those with vs. without hypertension (13.6 (12.3-14.9) vs. 11.8 (10.5-13.0) μg/ml, p = 0.03). Statistically independent determinants of kallistatin levels in diabetes were age, serum urea, total cholesterol, SAE and GGT, adjusted r2 = 0.24, p < 0.00001. CONCLUSIONS: Serum kallistatin levels are increased in Type 1 diabetic patients with microvascular complications and with hypertension, and correlate with renal and vascular dysfunction

Retrospective Determination of Prognostic Factors in BRAF-V600E Melanoma Brain Metastases​

View full abstracthttps://openworks.mdanderson.org/leading-edge/1030/thumbnail.jp

DataPackageR: Reproducible data preprocessing, standardization and sharing using R/Bioconductor for collaborative data analysis [version 2; referees: 2 approved, 1 approved with reservations]

A central tenet of reproducible research is that scientific results are published along with the underlying data and software code necessary to reproduce and verify the findings. A host of tools and software have been released that facilitate such work-flows and scientific journals have increasingly demanded that code and primary data be made available with publications. There has been little practical advice on implementing reproducible research work-flows for large ’omics’ or systems biology data sets used by teams of analysts working in collaboration. In such instances it is important to ensure all analysts use the same version of a data set for their analyses. Yet, instantiating relational databases and standard operating procedures can be unwieldy, with high "startup" costs and poor adherence to procedures when they deviate substantially from an analyst’s usual work-flow. Ideally a reproducible research work-flow should fit naturally into an individual’s existing work-flow, with minimal disruption. Here, we provide an overview of how we have leveraged popular open source tools, including Bioconductor, Rmarkdown, git version control, R, and specifically R’s package system combined with a new tool DataPackageR, to implement a lightweight reproducible research work-flow for preprocessing large data sets, suitable for sharing among small-to-medium sized teams of computational scientists. Our primary contribution is the DataPackageR tool, which decouples time-consuming data processing from data analysis while leaving a traceable record of how raw data is processed into analysis-ready data sets. The software ensures packaged data objects are properly documented and performs checksum verification of these along with basic package version management, and importantly, leaves a record of data processing code in the form of package vignettes. Our group has implemented this work-flow to manage, analyze and report on pre-clinical immunological trial data from multi-center, multi-assay studies for the past three years

Shaping of nanostructured materials or coatings through Spark Plasma Sintering

In the field of advanced ceramics, Spark Plasma Sintering (SPS) is known to be very efficient for superfast and full densification of ceramic nanopowders. This property is attributed to the simultaneous application of high density dc pulsed current and load, even though the sintering mechanisms involved remain unclear. In the first part of the paper, the mechanisms involved during SPS of two insulating oxide nanopowders (Al2O3 and Y2O3) are discussed while in the second part illustrations of the potential of SPS will be given for (i) Consolidation of mesoporous or unstable nanomaterials like SBA-15 or biomimetic apatite, respectively; (ii) Densification of core (BT or BST)/shell (SiO2 or Al2O3) nanoparticles with limited or controlled reaction at the interface. (iii) In-situ preparation of surface-tailored FeœFeAl2O4œAl2O3 nanocomposites, and finally (iv) One-step preparation of multilayer materials like a complete thermal barrier system on single crystal Ni-based superalloy

Shaping of nanostructured materials or coatings through Spark Plasma Sintering

In the field of advanced ceramics, Spark Plasma Sintering (SPS) is known to be very efficient for superfast and full densification of ceramic nanopowders. This property is attributed to the simultaneous application of high density dc pulsed current and load, even though the sintering mechanisms involved remain unclear. In the first part of the paper, the mechanisms involved during SPS of two insulating oxide nanopowders (Al2O3 and Y2O3) are discussed while in the second part illustrations of the potential of SPS will be given for (i) Consolidation of mesoporous or unstable nanomaterials like SBA-15 or biomimetic apatite, respectively; (ii) Densification of core (BT or BST)/shell (SiO2 or Al2O3) nanoparticles with limited or controlled reaction at the interface. (iii) In-situ preparation of surface-tailored FeœFeAl2O4œAl2O3 nanocomposites, and finally (iv) One-step preparation of multilayer materials like a complete thermal barrier system on single crystal Ni-based superalloy