Tactile experience induces c-fos expression in rat barrel cortex

Understanding gene expression that is responsive to sensory stimulation is central to elucidate molecular mechanisms underlying neuronal plasticity. In this study we demonstrate two new methods of stimulating whiskers that provide major sensory input to rat neocortex. In the first paradigm, animals were placed on the top of a cylinder and their vibrissae were brushed by hand, In the second paradigm, animals were placed for a brief period or time into a new, wired cage resulting in vibrissae stimulation when they explored the new environment. Both approaches induced c-Fos expression in barrel cortex corresponding to the stimulated vibrissae, especially in layer IV. Layers II/III and V/VI also showed c-Fos induction, but there were no detectable changes in layer VIb. The majority of c-Fos-expressing cells are probably not inhibitory neurons, because they do not show parvalbumin staining. Both paradigms, in contrast to the previous methods, are simple to use and do not require anesthesia, restraint of animals, or elaborate experimental setups

Assessing potential locations for flood-based farming using satellite imagery: a case study of Afar region, Ethiopia

The dry lowlands of Ethiopia are seasonally affected by long periods of low rainfall and, coinciding with rainfall in the Amhara highlands, flood waters which flow onto the lowlands resulting in damage to landscapes and settlements. In an attempt to convert water from storm generated floods into productive use, this study proposes a methodology using remote sensing data and geographical information system tools to identify potential sites where flood spreading weirs may be installed and farming systems developed which produce food and fodder for poor rural communities. First, land use land cover maps for the study area were developed using Landsat-8 and MODIS temporal data. Sentinel-1 data at 10 and 20m resolution on a 12-day basis were then used to determine flood prone areas. Slope and drainage maps were derived from Shuttle RADAR Topography Mission Digital Elevation Model at 90m spatial resolution. Accuracy assessment using ground survey data showed that overall accuracies (correctness) of the land use/land cover classes were 86% with kappa 0.82. Coinciding with rainfall in the uplands, March and April are the months with flood events in the short growing season (belg) and June, July and August have flood events during the major (meher) season. In the Afar region, there is potentially >0.55m ha land available for development using seasonal flood waters from belg or meher seasons. During the 4 years of monitoring (2015–2018), a minimum of 142,000 and 172,000 ha of land were flooded in the belg and meher seasons, respectively. The dominant flooded areas were found in slope classes of <2% with spatial coverage varying across the districts. We concluded that Afar has a huge potential for flood-based technology implementation and recommend further investigation into the investments needed to support new socio-economic opportunities and implications for the local agro-pastoral communities

Does the Constitution Provide More Ballot Access Protection for Presidential Elections Than for U.S. House Elections?

Both the U.S. Constitution and The Federalist Papers suggest that voters ought to have more freedom to vote for the candidate of their choice for the U.S. House of Representatives than they do for the President or the U.S. Senate. Yet, strangely, for the last thirty-three years, the U.S. Supreme Court and lower courts have ruled that the Constitution gives voters more freedom to vote for the candidate of their choice in presidential elections than in congressional elections. Also, state legislatures, which have been writing ballot access laws since 1888, have passed laws that make it easier for minor-party and independent candidates to get on the ballot for President than for the U.S. House. As a result, voters in virtually every state invariably have far more choices on their general election ballots for the President than they do for the House. This Article argues that the right of a voter to vote for someone other than a Democrat or a Republican for the House is just as important as a voter’s right to do so for President, and that courts should grant more ballot access protection to minor-party and independent candidates for the House

Prognostic impact of meningeal dissemination in primary CNS lymphoma (PCNSL): experience from the G-PCNSL-SG1 trial

Background We evaluated the frequency and prognostic impact of meningeal dissemination (MD) in immunocompetent adult patients with primary central nervous system lymphoma treated in a randomized phase III trial. Patients and methods MD was evaluated at study entry and defined by lymphoma proof in the meningeal compartment detected by at least one of the following methods: cerebrospinal fluid (CSF) cytomorphology, detection of clonal B cells by IgH PCR in CSF or contrast enhancement of the leptomeninges on magnetic resonance imaging (MRI). Results Data on MD were available in 415 patients, of those, MD was detected in 65 (15.7%): in 44/361 (12.2%) by CSF cytomorphology, in 16/152 (10.5%) by PCR and in 17/415 (4.1%) by MRI. Major patients' characteristics and therapy did not significantly differ between patients with MD (MD+) versus those without MD (MD−). There was a significant correlation of MD with CSF pleocytosis (>5/μl; P45 mg/dl). Median progression-free survival was 6.7 months [95% confidence interval (CI) 0-14.5] in MD+ and 8.3 months (5.7-10.8) in MD− patients (P=0.95); median overall survival was 21.5 months (95% CI 16.8-26.1) and 24.9 months (17.5-32.3), respectively (P=0.98). Conclusion MD was detected infrequently and had no impact on outcome in this tria

Residential greenness is differentially associated with childhood allergic rhinitis and aeroallergen sensitization in seven birth cohorts

Background The prevalence of allergic rhinitis is high, but the role of environmental factors remains unclear. We examined cohort‐specific and combined associations of residential greenness with allergic rhinitis and aeroallergen sensitization based on individual data from Swedish (BAMSE), Australian (MACS), Dutch (PIAMA), Canadian (CAPPS and SAGE), and German (GINIplus and LISAplus) birth cohorts (n = 13 016). Methods Allergic rhinitis (doctor diagnosis/symptoms) and aeroallergen sensitization were assessed in children aged 6–8 years in six cohorts and 10–12 years in five cohorts. Residential greenness was defined as the mean Normalized Difference Vegetation Index (NDVI) in a 500‐m buffer around the home address at the time of health assessment. Cohort‐specific associations per 0.2 unit increase in NDVI were assessed using logistic regression models and combined in a random‐effects meta‐analysis. Results Greenness in a 500‐m buffer was positively associated with allergic rhinitis at 6–8 years in BAMSE (odds ratio = 1.42, 95% confidence interval [1.13, 1.79]) and GINI/LISA South (1.69 [1.19, 2.41]) but inversely associated in GINI/LISA North (0.61 [0.36, 1.01]) and PIAMA (0.67 [0.47, 0.95]). Effect estimates in CAPPS and SAGE were also conflicting but not significant (0.63 [0.32, 1.24] and 1.31 [0.81, 2.12], respectively). All meta‐analyses were nonsignificant. Results were similar for aeroallergen sensitization at 6–8 years and both outcomes at 10–12 years. Stratification by NO2 concentrations, population density, an urban vs rural marker, and moving did not reveal consistent trends within subgroups. Conclusion Although residential greenness appears to be associated with childhood allergic rhinitis and aeroallergen sensitization, the effect direction varies by location

Titanium dioxide engineered for near-dispersionless high terahertz permittivity and ultra-low-loss

Realising engineering ceramics to serve as substrate materials in high-performance terahertz(THz) that are low-cost, have low dielectric loss and near-dispersionless broadband, high permittivity, is exceedingly demanding. Such substrates are deployed in, for example, integrated circuits for synthesizing and converting nonplanar and 3D structures into planar forms. The Rutile form of titanium dioxide (TiO2) has been widely accepted as commercially economical candidate substrate that meets demands for both low-loss and high permittivities at sub-THz bands. However, the relationship between its mechanisms of dielectric response to the microstructure have never been systematically investigated in order to engineer ultra-low dielectric-loss and high value, dispersionless permittivities. Here we show TiO2 THz dielectrics with high permittivity (ca. 102.30) and ultra-low loss (ca. 0.0042). These were prepared by insight gleaned from a broad use of materials characterisation methods to successfully engineer porosities, second phase, crystallography shear-planes and oxygen vacancies during sintering. The dielectric loss achieved here is not only with negligible dispersion over 0.2-0.8 THz, but also has the lowest value measured for known high-permittivity dielectrics. We expect the insight afforded by this study will underpin the development of subwavelength-scale, planar integrated circuits, compact high Q-resonators and broadband, slow-light devices in the THz band

B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR) signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 complex that links BCR signaling to the NF-κB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls an MYC-driven gene expression network predominantly through increasing MYC protein stability. Thus, our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL, but represents a common mechanism. MYC itself is pivotal for MCL survival because its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients

Feasibility of Azacitidine Added to Standard Chemotherapy in Older Patients with Acute Myeloid Leukemia — A Randomised SAL Pilot Study

Introduction: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML. Trial Design: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size. Patients and Methods: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of ,20,000/ml at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint. Results: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days. Conclusions: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm. Trial Registration: This trial is registered at clinical trials.gov (identifier: NCT00915252)