M-222 Slope Stabilization Case History – Geotechnical Lessons Learned from Michigan Department of Transportation Design Build Project

In 2009, the Michigan Department of Transportation (MDOT) became concerned about ongoing slope movements adjacent to a segment of M-222 located on outside bend of the Kalamazoo River in the City of Allegan, Michigan. Over the next couple years, continued river erosion and seasonally wet springs caused 8- to 10-foot high scarps adjacent to M-222, condemnation of a home, and several large block slides into the river. In the early spring of 2011, MDOT secured their first Construction Manager/General Contractor (CMGC) delivery method contract to protect M-222 and repair the slope. Improvements included constructing an up to 26-foot tall retaining wall, re-grading the roughly 70-foot high slope, and armoring the toe of slope. The improvements used were selected based on assessed risks and mobility requirements. Construction of the project began in July of 2011 and was completed in spring of 2012. A history of the slope instability progression using aerial photography, selection and design of the improvements, and resulting construction challenges are discussed. The authors conclusions on geotechnical lessons learned are shared

A thermal grooving study of relative grain boundary energies of nickel in polycrystalline Ni and in a Ni/YSZ anode measured by atomic force microscopy

Grain boundary grooves of nickel were studied in Ni polycrystals and in Ni/YSZ (nickel/yttria-stabilized zirconia) anode microstructures of an solid oxide fuel cell (SOFC) in order to determine the relative grain boundary energies of nickel. Reliable material parameters are necessary for realistic simulations to model the coarsening of nickel grains in SOFC anodes. However, the reported values in literature do not meet the requirements for accuracy and the experimental conditions differ strongly from the conditions within an anode. In this work, the measurement approach for atomic force microscopy was optimized to ensure the required accuracy in measuring grain boundary grooves; the thermal grooving experiments were performed at T=750 °C in dry and humid atmosphere. The resulting distributions of measured dihedral angles and relative grain boundary energies are identical in the polycrystal and the anode microstructure and are independent of annealing time and humidity. For the first time, precise values of the relative grain boundary energies of nickel are determined with high accuracy under operating conditions of an SOFC anode. The mean value of the relative grain boundary energies γ$_{GB}$ /γ$_{S}$ of nickel is 0.475 ± 0.013 for high-angle grain boundaries, 0.157 ± 0.013 for Σ3 low-angle grain boundaries, for grain boundaries and 0.019 ± 0.002 for twin boundaries

Using quantitative proteomics of Arabidopsis roots and leaves to predict metabolic activity

Proteins isolated from developing roots and leaves of Arabidopsis thaliana were separated by high-resolution two-dimensional (2-D) electrophoresis. The resulting 2-D proteome maps are markedly different. Quantitative analysis of root and leaf protein spot pairs revealed that in most instances there was at least a 1.5-fold differential. Peptide mass fingerprint analysis of the 288 most abundant 2-D spots from each organ allowed 156 and 126 protein assignments for roots and leaves, respectively, 54 of which were common. Metabolismrelated proteins accounted for 20% of assignments in samples from both organs, whereas energy-related proteins comprised 25 and 18% of leaf and root samples, respectively. Proteins involved in disease resistance and defense encompass 13% of root proteins, but only 7% of leaf proteins. Comparison of protein abundance with transcript abundance, using previously reported microarray data, yielded a correlation coefficient of approximately 0.6, suggesting that it is inappropriate to make protein level or metabolic conclusions based solely upon data from transcript profiling. A comparative model of root and leaf metabolism was developed, based upon protein rather than transcript abundance. The model indicates elevated one-carbon and tricarboxylic acid metabolism in roots relative to leaves

Reverted exhaustion phenotype of circulating lymphocytes as immune correlate of anti-PD1 first-line treatment in Hodgkin lymphoma

While classical Hodgkin lymphoma (HL) is highly susceptible to anti-programmed death protein 1 (PD1) antibodies, the exact modes of action remain controversial. To elucidate the circulating lymphocyte phenotype and systemic effects during anti-PD1 1st-line HL treatment we applied multicolor flow cytometry, FluoroSpot and NanoString to sequential samples of 81 HL patients from the NIVAHL trial (NCT03004833) compared to healthy controls. HL patients showed a decreased CD4 T-cell fraction, a higher percentage of effector-memory T cells and higher expression of activation markers at baseline. Strikingly, and in contrast to solid cancers, expression for 10 out of 16 analyzed co-inhibitory molecules on T cells (e.g., PD1, LAG3, Tim3) was higher in HL. Overall, we observed a sustained decrease of the exhausted T-cell phenotype during anti-PD1 treatment. FluoroSpot of 42.3% of patients revealed T-cell responses against ≥1 of five analyzed tumor-associated antigens. Importantly, these responses were more frequently observed in samples from patients with early excellent response to anti-PD1 therapy. In summary, an initially exhausted lymphocyte phenotype rapidly reverted during anti-PD1 1st-line treatment. The frequently observed IFN-y responses against shared tumor-associated antigens indicate T-cell-mediated cytotoxicity and could represent an important resource for immune monitoring and cellular therapy of HL

A Novel Task for the Investigation of Action Acquisition

We present a behavioural task designed for the investigation of how novel instrumental actions are discovered and learnt. The task consists of free movement with a manipulandum, during which the full range of possible movements can be explored by the participant and recorded. A subset of these movements, the ‘target’, is set to trigger a reinforcing signal. The task is to discover what movements of the manipulandum evoke the reinforcement signal. Targets can be defined in spatial, temporal, or kinematic terms, can be a combination of these aspects, or can represent the concatenation of actions into a larger gesture. The task allows the study of how the specific elements of behaviour which cause the reinforcing signal are identified, refined and stored by the participant. The task provides a paradigm where the exploratory motive drives learning and as such we view it as in the tradition of Thorndike [1]. Most importantly it allows for repeated measures, since when a novel action is acquired the criterion for triggering reinforcement can be changed requiring a new action to be discovered. Here, we present data using both humans and rats as subjects, showing that our task is easily scalable in difficulty, adaptable across species, and produces a rich set of behavioural measures offering new and valuable insight into the action learning process

In vitro studies on the modification of low-dose hyper-radiosensitivity in prostate cancer cells by incubation with genistein and estradiol

<p>Abstract</p> <p>Background</p> <p>As the majority of prostate cancers (PC) express estrogen receptors, we evaluated the combination of radiation and estrogenic stimulation (estrogen and genistein) on the radiosensitivity of PC cells in vitro.</p> <p>Methods</p> <p>PC cells LNCaP (androgen-sensitive) and PC-3 (androgen-independent) were evaluated. Estrogen receptor (ER) expression was analyzed by means of immunostaining. Cells were incubated in FCS-free media with genistein 10 μM and estradiol 10 μM 24 h before irradiation and up to 24 h after irradiation. Clonogenic survival, cell cycle changes, and expression of p21 were assessed.</p> <p>Results</p> <p>LNCaP expressed both ER-α and ER-β, PC-3 did not. Incubation of LNCaP and PC-3 with genistein resulted in a significant reduction of clonogenic survival. Incubation with estradiol exhibited in low concentrations (0.01 μM) stimulatory effects, while higher concentrations did not influence survival. Both genistein 10 μM and estradiol 10 μM increased low-dose hyper-radiosensitivity [HRS] in LNCaP, while hormonal incubation abolished HRS in PC-3. In LNCaP cells hormonal stimulation inhibited p21 induction after irradiation with 4 Gy. In PC-3 cells, the proportion of cells in G2/M was increased after irradiation with 4 Gy.</p> <p>Conclusion</p> <p>We found an increased HRS to low irradiation doses after incubation with estradiol or genistein in ER-α and ER-β positive LNCaP cells. This is of high clinical interest, as this tumor model reflects a locally advanced, androgen dependent PC. In contrast, in ER-α and ER-β negative PC-3 cells we observed an abolishing of the HRS to low irradiation doses by hormonal stimulation. The effects of both tested compounds on survival were ER and p53 independent. Since genistein and estradiol effects in both cell lines were comparable, neither ER- nor p53-expression seemed to play a role in the linked signalling. Nevertheless both compounds targeted the same molecular switch. To identify the underlying molecular mechanisms, further studies are needed.</p

why do romanian universities fail to internalize quality assurance

Despite legal provisions in place since 2005, Romanian universities are considered to perform internal quality assurance only at a formal level, on paper, and usually in anticipation of external evaluations demanded by the government or other official institutions. This paper posits five hypotheses to explain this situation. We analyze 187 interviews with people in universities in order to evaluate these hypotheses. Only two hypotheses are confirmed by the data, allowing us to construct a narrative of policy failure. First, there are top-down failures resulting from unclear and inconsistent legal provisions that focus on multilayered evaluation procedures. Second, there are bottom-up failures related to the lack of ownership over internal quality assurance systems by the actors in the universities. The existing procedures are often seen as control-tools of government, and understood as disconnected from the universities' own goals and problems. Consequently, people on the ground passively try to subvert these tools by carrying them out in a ritualistic manner—which is why quality assurance cannot become internalized

Population Genomic Analysis of Strain Variation in Leptospirillum Group II Bacteria Involved in Acid Mine Drainage Formation

Deeply sampled community genomic (metagenomic) datasets enable comprehensive analysis of heterogeneity in natural microbial populations. In this study, we used sequence data obtained from the dominant member of a low-diversity natural chemoautotrophic microbial community to determine how coexisting closely related individuals differ from each other in terms of gene sequence and gene content, and to uncover evidence of evolutionary processes that occur over short timescales. DNA sequence obtained from an acid mine drainage biofilm was reconstructed, taking into account the effects of strain variation, to generate a nearly complete genome tiling path for a Leptospirillum group II species closely related to L. ferriphilum (sampling depth ∼20×). The population is dominated by one sequence type, yet we detected evidence for relatively abundant variants (>99.5% sequence identity to the dominant type) at multiple loci, and a few rare variants. Blocks of other Leptospirillum group II types (∼94% sequence identity) have recombined into one or more variants. Variant blocks of both types are more numerous near the origin of replication. Heterogeneity in genetic potential within the population arises from localized variation in gene content, typically focused in integrated plasmid/phage-like regions. Some laterally transferred gene blocks encode physiologically important genes, including quorum-sensing genes of the LuxIR system. Overall, results suggest inter- and intrapopulation genetic exchange involving distinct parental genome types and implicate gain and loss of phage and plasmid genes in recent evolution of this Leptospirillum group II population. Population genetic analyses of single nucleotide polymorphisms indicate variation between closely related strains is not maintained by positive selection, suggesting that these regions do not represent adaptive differences between strains. Thus, the most likely explanation for the observed patterns of polymorphism is divergence of ancestral strains due to geographic isolation, followed by mixing and subsequent recombination