581 research outputs found
Engaging with issues of emotionality in mathematics teacher education for social justice
This article focuses on the relationship between social justice, emotionality and mathematics teaching in the context of the education of prospective teachers of mathematics. A relational approach to social justice calls for giving attention to enacting socially-just relationships in mathematics classrooms. Emotionality and social justice in teaching mathematics variously intersect, interrelate or interweave. An intervention, usng creative action methods, with a cohort of prospective teachers addressing these issues is described to illustrate the connection between emotionality and social justice in the context of mathematics teacher education. Creative action methods involve a variety of dramatic, interactive and experiential tools that can promote personal and group engagement and embodied reflection. The intervention aimed to engage the prospective teachers with some key issues for social justice in mathematics education through dialogue about the emotionality of teaching and learning mathematics. Some of the possibilities and limits of using such methods are considered
MK-0448, a Specific Kv1.5 Inhibitor: Safety, Pharmacokinetics and Pharmacodynamic Electrophysiology in Experimental Animal Models and in Humans.
BACKGROUND: -We evaluated the viability of I(Kur) as a target for maintenance of sinus rhythm in patients with a history of atrial fibrillation through the testing of MK-0448, a novel I(Kur) inhibitor. METHODS AND RESULTS: -In vitro MK-0448 studies demonstrated strong inhibition of I(Kur) with minimal off-target activity. In vivo MK-0448 studies in normal anesthetized dogs demonstrated significant prolongation of the atrial refractory period compared with vehicle controls without affecting the ventricular refractory period. In studies of a conscious dog heart failure model, sustained AF was terminated with bolus intravenous MK-0448 doses of 0.03 and 0.1 mg/kg. These data led to a two-part first-in-human study: Part I evaluated safety and pharmacokinetics, and Part II was an invasive electrophysiologic (EP) study in healthy subjects. MK-0448 was well-tolerated with mild adverse experiences, most commonly irritation at the injection site. During the EP study, ascending doses of MK-0448 were administered, but no increases in atrial or ventricular refractoriness were detected despite achieving plasma concentrations in excess of 2 μM. Follow-up studies in normal anesthetized dogs designed to assess the influence of autonomic tone demonstrated that prolongation of atrial refractoriness with MK-0448 was markedly attenuated in the presence of vagal nerve simulation, suggesting that the effects of I(Kur) blockade on atrial repolarization may be negated by enhanced parasympathetic neural tone. CONCLUSIONS: -The contribution of I(Kur) to human atrial electrophysiology is less prominent than in preclinical models and therefore is likely to be of limited therapeutic value for the prevention of atrial fibrillation
On the relevance of the mathematics curriculum to young people
In this paper we draw upon focus group data from a large study of learner trajectories through 14-19 mathematics education to think about the notion of relevance in the mathematics curriculum. Drawing on data from three socially distanced sites we explore how different emphases on what might be termed practical, process and/or professional forms of relevance affect the experiences and aspirations of learners of mathematics. We consider whether an emphasis on practical relevance in schools serving relatively disadvantaged communities might aid the reproduction of students’ social position. This leads us to suggest that a fourth category of curriculum relevance – political relevance – is largely missing from classrooms
Pre- and Posttranslational Regulation of Β-Endorphin Biosynthesis in the CNS: Effects of Chronic Naltrexone Treatment
There appear to be two anatomically distinct Β-endorphin (ΒE) pathways in the brain, the major one originating in the arcuate nucleus of the hypothalamus and a smaller one in the area of the nucleus tractus solitarius (NTS) of the caudal medulla. Previous studies have shown that these two proopiomelanocortin (POMC) systems may be differentially regulated by chronic morphine treatment, with arcuate cells down-regulated and NTS cells unaffected. In the present experiments, we examined the effects of chronic opiate antagonist treatment on ΒE biosynthesis across different CNS regions to assess whether the arcuate POMC system would be regulated in the opposite direction to that seen after opiate agonist treatment and to determine whether different ΒE-containing areas might be differentially regulated. Male adult rats were administered naltrexone (NTX) by various routes for 8 days (subcutaneous pellets, osmotic minipumps, or repeated intraperitoneal injections). Brain and spinal cord regions were assayed for total ΒE-ir, different molecular weight immunoreactive Β-endorphin (ΒE-ir) peptides, and POMC mRNA. Chronic NTX treatment, regardless of the route of administration, reduced total ΒE-ir concentrations by 30–40% in diencephalic areas (the arcuate nucleus, the remaining hypothalamus, and the thalamus) and the midbrain, but had no effect on ΒE-ir in the NTS or any region of the spinal cord. At the same time, NTX pelleting increased POMC mRNA levels in the arcuate to ∼ 140% of control values. These data suggest that arcuate POMC neurons are up-regulated after chronic NTX treatment (whereas NTS and spinal cord systems remain unaffected) and that they appear to be under tonic inhibition by endogenous opioids. Chromatographic analyses demonstrated that, after chronic NTX pelleting, the ratio of full length ΒE 1–31 to more processed ΒE-ir peptides (i.e., ΒE 1–27 and ΒE 1–26 ) tended to increase in a dose-dependent manner in diencephalic areas. Because ΒE 1–31 is the only POMC product that possesses opioid agonist properties, and ΒE 1–27 has been posited to function as an endogenous anatgonist of ΒE 1–31 , the NTX-induced changes in the relative concentrations of ΒE 1–31 and ΒE 1–27 /ΒE 1–26 may represent a novel regulatory mechanism of POMC cells to alter the opioid signal in the synapse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65603/1/j.1471-4159.1993.tb05820.x.pd
Connexin-43 prevents hematopoietic stem cell senescence through transfer of reactive oxygen species to bone marrow stromal cells
Hematopoietic stem cell (HSC) aging has become a concern in chemotherapy of older patients. Humoral and paracrine signals from the bone marrow (BM) hematopoietic microenvironment (HM) control HSC activity during regenerative hematopoiesis. Connexin-43 (Cx43), a connexin constituent of gap junctions (GJs) is expressed in HSCs, down-regulated during differentiation, and postulated to be a self-renewal gene. Our studies, however, reveal that hematopoietic-specific Cx43 deficiency does not result in significant long-term competitive repopulation deficiency. Instead, hematopoietic Cx43 (H-Cx43) deficiency delays hematopoietic recovery after myeloablation with 5-fluorouracil (5-FU). 5-FU-treated H-Cx43-deficient HSC and progenitors (HSC/P) cells display decreased survival and fail to enter the cell cycle to proliferate. Cell cycle quiescence is associated with down-regulation of cyclin D1, up-regulation of the cyclin-dependent kinase inhibitors, p21cip1. and p16INK4a, and Forkhead transcriptional factor 1 (Foxo1), and activation of p38 mitogen-activated protein kinase (MAPK), indicating that H-Cx43-deficient HSCs are prone to senescence. The mechanism of increased senescence in H-Cx43-deficient HSC/P cells depends on their inability to transfer reactive oxygen species (ROS) to the HM, leading to accumulation of ROS within HSCs. In vivo antioxidant administration prevents the defective hematopoietic regeneration, as well as exogenous expression of Cx43 in HSC/P cells. Furthermore, ROS transfer from HSC/P cells to BM stromal cells is also rescued by reexpression of Cx43 in HSC/P. Finally, the deficiency of Cx43 in the HM phenocopies the hematopoietic defect in vivo. These results indicate that Cx43 exerts a protective role and regulates the HSC/P ROS content through ROS transfer to the HM, resulting in HSC protection during stress hematopoietic regeneration
Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors
Connexin-43 (Cx43), a gap junction protein involved in control of cell proliferation, differentiation and migration, has been suggested to have a role in hematopoiesis. Cx43 is highly expressed in osteoblasts and osteogenic progenitors (OB/P). To elucidate the biologic function of Cx43 in the hematopoietic microenvironment (HM) and its influence in hematopoietic stem cell (HSC) activity, we studied the hematopoietic function in an in vivo model of constitutive deficiency of Cx43 in OB/P. The deficiency of Cx43 in OB/P cells does not impair the steady state hematopoiesis, but disrupts the directional trafficking of HSC/progenitors (Ps) between the bone marrow (BM) and peripheral blood (PB). OB/P Cx43 is a crucial positive regulator of transstromal migration and homing of both HSCs and progenitors in an irradiated microenvironment. However, OB/P Cx43 deficiency in nonmyeloablated animals does not result in a homing defect but induces increased endosteal lodging and decreased mobilization of HSC/Ps associated with proliferation and expansion of Cxcl12-secreting mesenchymal/osteolineage cells in the BM HM in vivo. Cx43 controls the cellular content of the BM osteogenic microenvironment and is required for homing of HSC/Ps in myeloablated animal
Patrimonio Paleontológico: un análisis diagnóstico de la gestión en el marco de la evaluación ambiental en Chile.
Aquatic mammal fossils in Latin America – a review of records, advances and challenges in research in the last 30 years
Records of aquatic mammal fossils (e.g. cetaceans, pinnipeds, sirenians, mustelids, and desmostylians) from Latin America (Mexico to Tierra del Fuego, including Antartica) span since the mid-1800s. Aquatic mammal fossils received little attention from the scientific community, with most of the first studies conducted by Northern Hemisphere researchers. Over the last 30 years, paleontological research in Latin America has increased considerably, with descriptions of several new species and revisions of published original records. The Latin American fossil record of marine mammals spans from the Eocene to the Pleistocene, with formations and specimens of global significance. All three main groups of cetaceans are represented in the continent (Archaeoceti, Mysticeti, and Odontoceti). Pinnipedia are represented by the families Otariidae and Phocidae, with records starting in the Middle Miocene. Both living families of Sirenia (Trichechidae and Dugongidae) are recorded. While less common, but still relevant, records of desmostylians and mustelids are known from Oligocene and Miocene deposits. This review provides a summary of the aquatic mammals known to date, with a special focus on the advances and developments of the last 30 years, since Cozzuol’s (1996) review of the South American fossil record. An up-to-date complete list of species based on the literature and unpublished data is also provided. The study also provides future directions for paleontological research in Latin America, and discusses the challenges and opportunities in the field, including the emergence of a strong new generation of Latin American researchers, many of whom are women.
Keywords:
Cetacea, Pinnipedia, Sirenia, Southern Hemispher
Canagliflozin Treatment Reduces Formation and Increases Degradation of Collagen Type III in the Canagliflozin Cardiovascular Assessment Study (CANVAS)
Cornucopia: Temporal safety for CHERI heaps
Use-after-free violations of temporal memory safety continue to plague software systems, underpinning many high-impact exploits. The CHERI capability system shows great promise in achieving C and C++ language spatial memory safety, preventing out-of-bounds accesses. Enforcing language-level temporal safety on CHERI requires capability revocation, traditionally achieved either via table lookups (avoided for performance in the CHERI design) or by identifying capabilities in memory to revoke them (similar to a garbage-collector sweep). CHERIvoke, a prior feasibility study, suggested that CHERI’s tagged capabilities could make this latter strategy viable, but modeled only architectural limits and did not consider the full implementation or evaluation of the approach. Cornucopia is a lightweight capability revocation system for CHERI that implements non-probabilistic C/C++ temporal memory safety for standard heap allocations. It extends the CheriBSD virtual-memory subsystem to track capability flow through memory and provides a concurrent kernel-resident revocation service that is amenable to multi-processor and hardware acceleration. We demonstrate an average overhead of less than 2% and a worst-case of 8.9% for concurrent
revocation on compatible SPEC CPU2006 benchmarks on a multi-core CHERI CPU on FPGA, and we validate Cornucopia against the Juliet test suite’s corpus of temporally unsafe programs. We test its compatibility
with a large corpus of C programs by using a revoking allocator as the system allocator while booting multi-user CheriBSD. Cornucopia is a viable strategy for always-on temporal heap memory safety, suitable for production environments.This work was supported by the Defense Advanced Research Projects Agency (DARPA) and the Air Force Research Laboratory (AFRL), under contracts FA8750-10-C-0237 (“CTSRD”) and HR0011-18-C-0016 (“ECATS”). We also acknowledge the EPSRC REMS Programme Grant (EP/K008528/1), the ABP Grant (EP/P020011/1), the ERC ELVER Advanced Grant (789108), the Gates Cambridge Trust, Arm Limited, HP Enterprise, and Google, Inc
- …
