A comparison of nanotribology and nanoindentation

Metal friction and wear is the collective contact and interaction of asperities of micrometer dimension. We use a nanoindenter with tangential force measurement to simulate the behavior in engineering contacts and to fundamentally understand friction and wear. This presentation investigates the deformation due to a single stroke scratch of a diamond nanoindenter in austenite base. We find that the elastic and plastic equations for static indentation also apply for the dynamic scratching. Additionally, the friction coefficient is found to be normal force dependent and we observe three domains: microstructure dominated friction, plastic plowing dominated wear and wear particle dominated tribology. Focussing on plasticity, we observe that the local crystal orientation has a significant influence on the development and spread of of plasticity. Additionally, the complex three-dimensional stress state results in the formation of non-obvious plastic slip patterns. Finally, we show crack formation in the scratch track even after a single stroke

Enactment of Lessons from a Technology-Based Curriculum: The Role of Instructional Practices in Students’ Opportunity to Learn

Digital tools and technology-based activities offer new and promising opportunities for students to actively explore mathematical concepts and ideas in ways supported by current reforms and visions of mathematics instruction. This report provides an in-depth look at the implementation of SunBay Digital Mathematics (SunBay Math) during the second year of an i3 validation project, in two large Florida districts. SunBay Math is a set of middle-school curriculum replacement units centered on the use of technology-based, dynamically linked representations to learn core mathematical concepts. We focus specifically on patterns and relationships between instructional practices and instructional quality in 26 videotaped lesson enactments that were purposefully collected to represent variation in implementation

L'éducation des femmes et le développement en Afrique subsaharienne

Les hommes et les femmes sont inégaux face au développement, et d'autant plus dans les PED. En Afrique subsaharienne, le développement des femmes à travers l'éducation est indispensable afin de converger, voire de dépasser les OMD.femmes, Afrique subsaharienne, éducation, développement, OMD, objectifs du millénaire pour le développement, pays en développement

Lithium treatment reduces the renal kallikrein excretion rate

Lithium treatment reduces the renal kallikrein excretion rate. Lithium salts are widely used agents for the prophylactic treatment of affective disorders. Lithium salts may be associated with distal nephron dysfunction. Kallikrein is a protease which is generated by the distal nephron. We used an amidolytic assay of chromatographically purified enzyme to determine the urinary excretion rate of active kallikrein in relation to lithium treatment. All plasma lithium concentrations were within the therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the urinary excretion rate of active kallikrein was 267.4 65.6 mU/24 hrs before lithium treatment, and fell to 117.8 39.6 mU/24 hrs (P < 0.05) on day 14 of lithium treatment. This reduction was associated with a decrease of immunoreactive kallikrein in the same urines by 66%. In another 15 patients who had undergone lithium therapy for an average period of 5.6 years, the urinary excretion rate of active kallikrein was 86.1 14.5 mU/24 hrs, while 21 age-matched healthy controls had an excretion rate of 364.1 58.4 mU/24 hrs (P < 0.05). Measurements of immunoreactive kallikrein in the same urine samples demonstrated a reduction of kallikrein after long-term lithium treatment by 78%. These observations could not be attributed to changes in creatinine clearance, renal sodium or potassium excretion rates or plasma concentrations of aldosterone and vasopressin. Addition of lithium to the urine in vitro had no demonstrable effect on kallikrein measurement by amidolytic assay. We conclude that lithium in therapeutic plasma concentrations may directly suppress the secretion of kallikrein by renal connecting tubule cells

Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated-skeletal muscle insulin resistance

Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) and increased macrophage infiltration. However, the relative effects of SFA and unsaturated fatty acid (UFA)-activated macrophages on muscle are unknown. Here, macrophages were treated with palmitic acid, palmitoleic acid or both and the effects of the conditioned medium (CM) on C2C12 myotubes investigated. CM from palmitic acid-treated J774s (palm-mac-CM) impaired insulin signalling and insulin-stimulated glycogen synthesis, reduced Inhibitor κBα and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in myotubes. p38 MAPK inhibition or siRNA partially ameliorated these defects, as did addition of tumour necrosis factor-α blocking antibody to the CM. Macrophages incubated with both FAs generated CM that did not induce IR, while palmitoleic acid-mac-CM alone was insulin sensitising. Thus UFAs may improve muscle insulin sensitivity and counteract SFA-mediated IR through an effect on macrophage activation

Validation of elevated levels of interleukin-8 in the cerebrospinal fluid, and discovery of new biomarkers in patients with GBS and CIDP using a proximity extension assay

BackgroundBiomarkers for diagnosis of inflammatory neuropathies, assessment of prognosis, and treatment response are lacking.MethodsCSF and EDTA plasma from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), healthy controls (HC) and disease controls were analyzed with Olink multiplex proximity extension assay (PEA) from two independent cohorts. Levels of interleukin-8 (IL8) were further analyzed with ELISA in patients with GBS, CIDP, paraproteinemia-related demyelinating polyneuropathy (PDN), multifocal motor neuropathy (MMN), HC and disease controls. ROC analysis was performed. Outcome was measured with the GBS-disability score (GBS-ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) score.ResultsIn CSF, multiplex PEA analysis revealed up-regulation of IL8 in GBS compared to CIDP and HC respectively, and CIDP compared to HC. In addition, levels of IL2RA were upregulated in GBS compared to both HC and CIDP, SELE in GBS compared to HC, and ITGAM, IL6, and NRP1 in GBS compared to CIDP. In plasma, levels of MMP3, THBD and ITGAM were upregulated in CIDP compared to HC. Validation of multiplex IL8 results using ELISA, revealed increased levels of IL8 in CSF in patients with GBS and CIDP versus HC and non-inflammatory polyneuropathies (NIP) respectively, as well as in PDN versus NIP and HC. Levels of IL8 in CSF correlated with impairment in the acute phase of GBS as well as outcome at 6-months follow up.ConclusionIL8 in CSF is validated as a diagnostic biomarker in GBS and CIDP, and a prognostic biomarker in GBS. Multiplex PEA hereby identifies several potential biomarkers in GBS and CIDP

Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal.

Recent advances in single-cell technologies have permitted the investigation of heterogeneous cell populations at previously unattainable resolution. Here we apply such approaches to resolve the molecular mechanisms driving disease in mouse hematopoietic stem cells (HSCs), using JAK2V617F mutant myeloproliferative neoplasms (MPNs) as a model. Single-cell gene expression and functional assays identified a subset of JAK2V617F mutant HSCs that display defective self-renewal. This defect is rescued at the single HSC level by crossing JAK2V617F mice with mice lacking TET2, the most commonly comutated gene in patients with MPN. Single-cell gene expression profiling of JAK2V617F-mutant HSCs revealed a loss of specific regulator genes, some of which were restored to normal levels in single TET2/JAK2 mutant HSCs. Of these, Bmi1 and, to a lesser extent, Pbx1 and Meis1 overexpression in JAK2-mutant HSCs could drive a disease phenotype and retain durable stem cell self-renewal in functional assays. Together, these single-cell approaches refine the molecules involved in clonal expansion of MPNs and have broad implications for deconstructing the molecular network of normal and malignant stem cells.MS is the recipient of a BBSRC Industrial CASE PhD Studentship, and CAO and JF are recipients of Wellcome Trust PhD Studentships. Work in the Kent lab is supported by a Bloodwise Bennett Fellowship (15008), a European Hematology Association Non-Clinical Advanced Research Fellowship, and an ERC Starting Grant (ERC-2016-STG–715371). Work in the Green Lab is supported by the Wellcome Trust, Bloodwise, Cancer Research UK, the Kay Kendall Leukaemia Fund, and the Leukemia and Lymphoma Society of America. Dr. Kent, Professor Göttgens, and Professor Green are all supported by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute the National Institute for Health Research Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre

Right temporal alpha oscillations as a neural mechanism for inhibiting obvious associations

Creative cognition requires mental exploration of remotely connected concepts while suppressing dominant ones. Across four experiments using different samples of participants, we provide evidence that right temporal alpha oscillations play a crucial role in inhibiting habitual thinking modes, thereby paving the way for accessing more remote ideas. In the first experiment, participants completed the compound remote associate task (RAT) in three separate sessions: during right temporal cortex alpha (10 Hz) tACS, left temporal alpha tACS, and sham tACS. Participants performed better under right tACS only on RAT items in which two of the three words shared misleading semantic associations. In the second experiment, we measured EEG while the participants solved RAT items with or without shared misleading associations. We observed an increase in right temporal alpha power when participants correctly solved RAT items with misleading semantic associations. The third experiment demonstrated that while solving divergent thinking tasks, participants came up with more remote ideas when stimulated by right temporal alpha tACS. In the fourth experiment, we found that participants showed higher right temporal alpha power when generating more remote uses for common objects. These studies altogether indicate that right temporal alpha oscillations may support creativity by acting as a neural mechanism for an active inhibition of obvious semantic associations