Cyclic angiotensin-(1-7) contributes to rehabilitation of animal performance in a rat model of cerebral stroke

Peptidase-resistant, lanthionine-stabilized angiotensin-(1-7), termed cAng-(1-7), has shown therapeutic efficacy in animal models of cardiovascular, metabolic, kidney and pulmonary disease. Goal of the present study was testing the capacity of subcutaneously administered cAng-(1-7) to induce rehabilitation of animal performance in the transient middle cerebral artery occlusion rat model of cerebral stroke. 24 h after ischemic stroke induction, cAng-(1-7) was administered for 28 days at a dose of 500 μg/kg/day, either daily via subcutaneous injection or continuously via an alzet pump. Both ways of administration of cAng-(1-7) were equally effective. Measurements were continued until day 50. Compared to vehicle, cAng-(1-7) clearly demonstrated significantly increased capillary density (p < 0.01) in the affected hemisphere and improved motor and somatosensory functioning. The modified neurological severity score (p < 0.001 at days 15 and 50), stepping test (p < 0.001 at days 36–50), forelimb placement test (p < 0.001 at day 50), body swing test (p < 0.001 at days 43 and 50) all demonstrated that cAng-(1-7) caused significantly improved animal performance. Taken together the data convincingly indicate rehabilitating capacity of subcutaneously injected cAng-(1-7) in cerebral ischemic stroke

PASSt – Predictive Analytics Services für Studienerfolgsmanagement

Hochschulen haben zunehmendes Interesse daran, den Studienerfolg ihrer Studierenden analysieren und quantifizieren zu können. In diesem Zusammenhang versucht das Projekt PASSt – Predictive Analytics Services für Studienerfolgsmanagement – einen Rahmen für die empirische Analyse und Vorhersage des Studienerfolges herzustellen: Studenten- und Studiendaten werden in eine generische Datenstruktur importiert, auf die Machine Learning und Simulationen angewendet werden. Die beiden wichtigsten Ergebnisse der Anwendung dieser Ansätze sind eine Vorhersage des Studienerfolgs und eine Strukturanalyse von Lehrplänen, die zur Verbesserung der Studienbedingungen für Studierende genutzt werden können. Das Framework verfügt darüber hinaus über eine zusammenfassende Visualisierung, die eine einfache Interpretation und Nutzung der Ergebnisse für die Curriculumsplanung ermöglicht. Dieses Projekt wurde am 1. Juni 2023 im Rahmen einer Online-Veranstaltung des BMBWF präsentiert. Die Präsentationsunterlagen finden Sie hier

Short-term occupations at high elevation during the Middle Paleolithic at Kalavan 2 (Republic of Armenia)

The Armenian highlands encompasses rugged and environmentally diverse landscapes and is characterized by a mosaic of distinct ecological niches and large temperature gradients. Strong seasonal fluctuations in resource availability along topographic gradients likely prompted Pleistocene hominin groups to adapt by adjusting their mobility strategies. However, the role that elevated landscapes played in hunter-gatherer settlement systems during the Late Pleistocene (Middle Palaeolithic [MP]) remains poorly understood. At 1640 m above sea level, the MP site of Kalavan 2 (Armenia) is ideally positioned for testing hypotheses involving elevation-dependent seasonal mobility and subsistence strategies. Renewed excavations at Kalavan 2 exposed three main occupation horizons and ten additional low densities lithic and faunal assemblages. The results provide a new chronological, stratigraphical, and paleoenvironmental framework for hominin behaviors between ca. 60 to 45 ka. The evidence presented suggests that the stratified occupations at Kalavan 2 locale were repeated ephemerally most likely related to hunting in a high-elevation within the mountainous steppe landscape.info:eu-repo/semantics/publishedVersio

Structure of inhomogeneous polymer networks prepared from telechelic polybutadiene

The structure and dynamics of segmented polyurethane networks prepared from poly(butadiene) diols (PBD) of different molecular weights M-n = 1200, 2160,2650,4690 and 10,300 g mol(-1), 4,4'-diphenylmethane diisocyanate (MDI) and poly(oxypropylene) triol (POPT) (M, = 710 g mol-1) have been investigated by dynamic mechanical analysis, dielectric relaxation spectroscopy, differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SAXS and WAXS). Microphase separation on Danometre scale has been confirmed by SAXS in all networks. Except for the highest molecular weight of PBD, the networks consist of microdomains of similar size and composition dispersed in the soft phase of polybutadiene segments. Dielectric spectroscopy revealed the existence of three types of noncrystalline phases, each characterised by a well-developed dynamic glass transition. Absence of crystallinity has been proven by WAXS and DSC. (C) 2002 Elsevier Science Ltd. All rights reserved.status: publishe

Continuous administration of a p38α inhibitor during the subacute phase after transient ischemia-induced stroke in the rat promotes dose-dependent functional recovery accompanied by increase in brain BDNF protein level.

There is unmet need for effective stroke therapies. Numerous neuroprotection attempts for acute cerebral ischemia have failed and as a result there is growing interest in developing therapies to promote functional recovery through increasing synaptic plasticity. For this research study, we hypothesized that in addition to its previously reported role in mediating cell death during the acute phase, the alpha isoform of p38 mitogen-activated protein kinase, p38α, may also contribute to interleukin-1β-mediated impairment of functional recovery during the subacute phase after acute ischemic stroke. Accordingly, an oral, brain-penetrant, small molecule p38α inhibitor, neflamapimod, was evaluated as a subacute phase stroke treatment to promote functional recovery. Neflamapimod administration to rats after transient middle cerebral artery occlusion at two dose levels was initiated outside of the previously characterized therapeutic window for neuroprotection of less than 24 hours for p38α inhibitors. Six-week administration of neflamapimod, starting at 48 hours after reperfusion, significantly improved behavioral outcomes assessed by the modified neurological severity score at Week 4 and at Week 6 post stroke in a dose-dependent manner. Neflamapimod demonstrated beneficial effects on additional measures of sensory and motor function. It also resulted in a dose-related increase in brain-derived neurotrophic factor (BDNF) protein levels, a previously reported potential marker of synaptic plasticity that was measured in brain homogenates at sacrifice. Taken together with literature evidence on the role of p38α-dependent suppression by interleukin-1β of BDNF-mediated synaptic plasticity and BDNF production, our findings support a mechanistic model in which inhibition of p38α promotes functional recovery after ischemic stroke by blocking the deleterious effects of interleukin-1β on synaptic plasticity. The dose-related in vivo efficacy of neflamapimod offers the possibility of having a therapy for stroke that could be initiated outside the short time window for neuroprotection and for improving recovery after a completed stroke

Quasi-experimental and experimental approaches to environmental economics

This paper argues that an increased application of quasi-experimental and experimental techniques will improve understanding about core environmental economics questions. This argument is supported by a review of the limitations of associational evidence in assessing causal hypotheses. The paper also discusses the benefits of experiments and quasi-experiments, outlines some quasi-experimental methods, and highlights threats to their validity. It then illustrates the quasi-experimental method by assessing the validity of a quasi-experiment that aims to estimate the impact of the Endangered Species Act on property markets in North Carolina. The paper's larger argument is that greater application of experimental and quasi-experimental techniques can identify efficient policies that increase social welfare