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Algebra is considered by many to be a gateway to higher-level mathematics and eventual economic success yet students with and without disabilities often struggle to develop algebra skills. This study builds on the limited understanding of how virtual manipulatives support students with disabilities in the area of algebra by investigating their use within the virtual-abstract (VA) framework. Using a multiple probe across behaviors, replicated across participant design, researchers found a functional relation between the VA framework and student algebraic learning. Mathematical behaviors based on grade-level curriculum included: one-step equations with positive and negative numbers, two-step equations with positive numbers, and two-step equations with positive and negative numbers. All three seventh-grade students with high-incidence disabilities improved their performance on each of the three algebra behaviors during intervention, and all participants maintained their accuracy after intervention, as compared to baseline to maintenance. Detailed results and their implications for practice are discussed further. [ABSTRACT FROM AUTHOR]

The ability to change an organism's DNA through gene editing is of great importance for the prevention and treatment of genetic and acquired diseases. Rapid progress has been made during the last decade due to the discovery and refinement of CRISPR/Cas9 as an accurate, fast, and reliable genome editing technique. In this issue of the JCI, Lebek et al. present the culmination from a line of work in the Olson laboratory focused on in vivo gene editing of CAMK2D. The paper presents a combined state-of-the-art gene therapy approach that demonstrates how gene therapy can yield cardioprotection in a mouse model and takes notable steps toward potential applicability in patients. [ABSTRACT FROM AUTHOR]

Objective: Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management of this important emerging disorder.Methods: Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans. We then undertook a detailed analysis of the clinical, histopathological and imaging features of these patients.Results: All patients had prenatal or early onset hypotonia and/or congenital contractures. None had ophthalmoplegia. Scoliosis and respiratory insufficiency typically developed early and progressed rapidly, whereas limb weakness was often slowly progressive, and usually did not prevent independent walking. Cardiac involvement was present in 46% of patients. Relatives of 2 patients had dilated cardiomyopathy. Creatine kinase levels were normal to moderately elevated. Increased fiber size variation, internalized nuclei and cores were common histopathological abnormalities. Cap-like regions, whorled or ring fibers, and mitochondrial accumulations were also observed. Muscle magnetic resonance imaging showed gluteal, hamstring and calf muscle involvement. Western blot analysis showed a near-normal sized titin protein in all samples. The presence of 2 mutations predicted to impact both N2BA and N2B cardiac isoforms appeared to be associated with greatest risk of cardiac involvement. One-third of patients had 1 mutation predicted to impact exons present in fetal skeletal muscle, but not included within the mature skeletal muscle isoform transcript. This strongly suggests developmental isoforms are involved in the pathogenesis of this congenital/early onset disorder.Interpretation: This detailed clinical reference dataset will greatly facilitate diagnostic confirmation and management of patients, and has provided important insights into disease pathogenesis. Ann Neurol 2018;83:1105-1124. [ABSTRACT FROM AUTHOR]

The contractile machinery of heart and skeletal muscles has as an essential component the thick filament, comprised of the molecular motor myosin. The thick filament is of a precisely controlled length, defining thereby the force level that muscles generate and how this force varies with muscle length. It has been speculated that the mechanism by which thick filament length is controlled involves the giant protein titin, but no conclusive support for this hypothesis exists. Here we show that in a mouse model in which we deleted two of titin’s C-zone super-repeats, thick filament length is reduced in cardiac and skeletal muscles. In addition, functional studies reveal reduced force generation and a dilated cardiomyopathy (DCM) phenotype. Thus, regulation of thick filament length depends on titin and is critical for maintaining muscle health. [ABSTRACT FROM AUTHOR]

Titin is a molecular spring that determines the passive stiffness of muscle cells. Changes in tidn's stiffness occur in various myopathies, but whether these are a cause or an effect of the disease is unknown. We studied a novel mouse model in which titin's stiffness was slightly increased by deleting nine immunoglobulin (Ig)-like domains from ti-tin's constitutively expressed proximal tandem Ig segment (IG KO). KO mice displayed mild kyphosis, a phenotype commonly associated with skeletal muscle myopathy. Slow muscles were atrophic with alterations in myosin iso-form expression; functional studies in soleus muscle revealed a reduced specific twitch force. Exon expression analysis showed that KO mice underwent additional changes in titin splicing to yield smaller than expected titin isoforms that were much stiffer than expected. Additionally, splicing occurred in the PEVK region of titin, a find-ing confirmed at the protein level. The titin-binding protein Ankrdl was highly increased in the IG KO, but this did not play a role in generating small titin isoforms because titin expression was unaltered in IG KO mice crossed with Ankrdl-deficient mice. In contrast, the splicing factor RBM20 (RNA-binding motif 20) was also significantly in-creased in IGKOmice, and additional differential splicing was reversed in IG KOmice crossed with a mouse with reduced RBM20 activity. Thus, increasing titin's stiffness triggers pathological changes in skeletal muscle, with an important role played by RBM20. [ABSTRACT FROM AUTHOR]

The article compares the performance of tree retardant crosslinked polyethylene (TRXLPE) and crosslinked polyethylene (XLPE) insulation material used in medium voltage underground power cables. TRXLPE has become the insulation specified by utilities in North America for virtually all underground XLPE medium voltage power cables. TRXLPE insulation materials are expected to retard the growth of water trees which will slow down the aging of cables when operated in wet environments. Compound and cable manufacturers use a variety of accelerated aging tests to assess the performance of TRXLPE insulation materials.

Writers for both academic and popular audiences often use the term gender when considering differences between the educational experiences of male and female students, and the distinction often appears to be based on a traditional understanding of the term sex. The authors of this article argue that gender and sex should be distinguished more clearly in education research and that the pattern of unclear, conflated, and even synonymous use of the terms has slowed progress in understanding how gender influences students' educational experiences. The authors present evidence of conflated use, review the wide diversity in orienting perspectives and definitions of gender, show how current American Psychological Association publication guidelines fail to provide clear guidance on the use of the terms, and make recommendations for improving research practice. [ABSTRACT FROM AUTHOR]

Research on the impact of Standards-based mathematics and reform calculus curricula has largely focused on changes in achievement and attitudes, generally ignoring how students experience these new programs. This study was designed to address that deficit. As part of a larger effort to characterize students' transitions into and out of reform programs, we analyzed how 93 high school and college students perceived Standards-based and reform calculus programs as different from traditional ones. Results show considerable diversity across and even within sites. Nearly all students reported differences, but high-impact differences, like Content, were not always related to curriculum type (reform or traditional). Students' perceptions aligned moderately well with those of reform curriculum authors, e.g., concerning Typical Problems. These results show that students' responses to reform programs can be quite diverse and only partially aligned with adults' views. [ABSTRACT FROM AUTHOR]

Research on the impact of Standards-based, K-12 mathematics programs (i.e., written curricula and associated teaching practices) and of reform calculus programs has focused primarily on student achievement and secondarily, and rather ineffectively, on student attitudes. This research has shown that reform programs have competed well with traditional programs in terms of student achievement. Results for attitude change have been much less conclusive because of conceptual and methodological problems. We critically review this literature to argue for broader conceptions of impact that target new dimensions of program effect and examine interactions between dimensions. We also briefly present the conceptualization, design, and broad results of one study, the Mathematical Transitions Project (MTP), which expanded the range of impact along those lines. The MTP results reveal substantial diversity in students' experience within and between research sites, different patterns of experience between high school and university students, and surprising relationships between achievement and attitude for some students. [ABSTRACT FROM AUTHOR]

Shares an author's thoughts on issues of quality in mathematics education research. View on the nature and importance of reviews of submission for mathematics education research; Need for identifying the generality of research principles and concepts; Focus on the importance of shouldering the increased personal cost to raise the collective quality of reviews.

John Dewey''s (The Essential Dewey, Vol. I, University of Chicago Press, Chicago, IL, 1902) proposal that rich and engaged learning requires teachers to “psychologize” their subject-matter is now 100 years old. Yet his message remains insightful, challenging, and timely in the United States—especially given recent curricular reforms in mathematics and science. We represent his proposal, contrast it with more subject-centered reforms, and emphasize the task of teachers’ understanding of students’ subject-relevant experience. Since published examples of teachers’ “psychologizing” remain relatively scarce, we sketch two—one each from secondary science and mathematics. They show how teachers can combine promising “big ideas” with sensitive analyses of students’ experience to transform subject-matters, especially for academically less successful students. In closing, we argue that support for and focus on this work must begin in teacher preparation programs. [Copyright &y& Elsevier]

A speech about the conference theme "Teachers, Traditions, and Transformation," given by educator John F. Smith III at the Ninth Annual Master's Capstone Conference for the Urban Teacher Master's and Certification Program at the University of Pennsylvania on April 29, 2014, is presented.

Global competition and technological innovation, it is often argued, have fundamentally changed the nature of work, making it more technically demanding, while schools have not kept pace. But the mathematics used in work places, much less whole industries, is rarely examined carefully. Observations at 16 sites involved in automobile manufacturing indicate that the level and content of mathematics required by work practices vary substantially. High-volume assembly made minimal to modest demands on workers, primarily for measurement and numerical/quantitative reasoning. Machine tool operation and work in quality labs, however, required substantial spatial and geometric knowledge in two and three dimensions. Technology affected the mathematical demands of work but the effect was shaped by management orientation and patterns of work organization. These results raise questions about how badly schools are failing to prepare students for "the global competitive workplace." [ABSTRACT FROM AUTHOR]

Describes the mathematics of two broad categories of manufacturing jobs and its implications for curriculum and teaching. Mathematics of assembly work; Basic mathematics of machining; Curricular considerations in connecting school and work.

Analyzes the tension between the traditional foundation of efficacy in teaching mathematics and current efforts in mathematics education. Teachers' sense of efficacy; Teaching mathematics by telling; Issues in teacher reactions to reform.

This article uses a critical evaluation of research on student misconceptions in science and mathematics to articulate a constructivist view of learning in which student conceptions play productive roles in the acquisition of expertise. We acknowledge and build on the empirical results of misconceptions research but question accompanying views of the character, origins, and growth of students' conceptions. Students have often been viewed as holding flawed ideas that are strongly held, that interfere with learning, and that instruction must confront and replace. We argue that this view overemphasizes the discontinuity between students and expert scientists and mathematicians, making the acquisition of expertise difficult to conceptualize. It also conflicts with the basic premise of constructivism: that students build more advanced knowledge from prior understandings. Using case analyses, we dispute some commonly cited dimensions of discontinuity and identify important continuities that were previously ignored or underemphasized. We highlight elements of knowledge that serve both novices and experts, albeit in different contexts and under different conditions. We provide an initial sketch of a constructivist theory of learning that interprets students' prior conceptions as resources for cognitive growth within a complex systems view of knowledge. This theoretical perspective aims to characterize the interrelationships among diverse knowledge elements rather than identify particular flawed conceptions; it emphasizes knowledge refinement and reorganization, rather than replacement, as primary metaphors for learning; and it provides a framework for understanding misconceptions as both flawed and productive. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Low myocardial cGMP-PKG (cyclic guanosine monophosphate-protein kinase G) activity has been associated with increased cardiomyocyte diastolic stiffness in heart failure with preserved ejection fraction. Cyclic guanosine monophosphate is mainly hydrolyzed by PDE (phosphodiesterases) 5a and 9a. Importantly, PDE9a expression has been reported to be upregulated in human heart failure with preserved ejection fraction myocardium and chronic administration of a PDE9a inhibitor reverses preestablished cardiac hypertrophy and systolic dysfunction in mice subjected to transverse aortic constriction (TAC). We hypothesized that inhibiting PDE9a activity ameliorates diastolic dysfunction. Methods: To examine the effect of chronic PDE9a inhibition, 2 diastolic dysfunction mouse models were studied: (1) TAC-deoxycorticosterone acetate and (2) Lepr db/db . PDE9a inhibitor (5 and 8 mg/kg per day) was administered to the mice via subcutaneously implanted osmotic minipumps for 28 days. The effect of acute PDE9a inhibition was investigated in intact cardiomyocytes isolated from TAC-deoxycorticosterone acetate mice. Atrial natriuretic peptide together with PDE9a inhibitor were administered to the isolated intact cardiomyocytes through the cell perfusate. Results: For acute inhibition, no cellular stiffness reduction was found, whereas chronic PDE9a inhibition resulted in reduced left ventricular chamber stiffness in TAC-deoxycorticosterone acetate, but not in Lepr db/db mice. Passive cardiomyocyte stiffness was reduced by chronic PDE9a inhibition, with no differences in myocardial fibrosis or cardiac morphometry. PDE9a inhibition increased the ventricular-arterial coupling ratio, reflecting impaired systolic function. Conclusions: Chronic PDE9a inhibition lowers left ventricular chamber stiffness in TAC-deoxycorticosterone acetate mice. However, the usefulness of PDE9a inhibition to treat high-diastolic stiffness may be limited as the required PDE9a inhibitor dose also impairs systolic function, observed as a decline in ventricular-arterial coordination, in this model. [ABSTRACT FROM AUTHOR]

The article presents a lesson plan for primary education which teaches concepts of linear measurement.

Titin's C-zone is an inextensible segment in titin, comprised of 11 super-repeats and located in the cMyBP-C-containing region of the thick filament. Previously we showed that deletion of titin's super-repeats C1 and C2 (Ttn ΔC1–2 model) results in shorter thick filaments and contractile dysfunction of the left ventricular (LV) chamber but that unexpectedly LV diastolic stiffness is normal. Here we studied the contraction-relaxation kinetics from the time-varying elastance of the LV and intact cardiomyocyte, cellular work loops of intact cardiomyocytes, Ca2+ transients, cross-bridge kinetics, and myofilament Ca2+ sensitivity. Intact cardiomyocytes of Ttn ΔC1–2 mice exhibit systolic dysfunction and impaired relaxation. The time-varying elastance at both LV and single-cell levels showed that activation kinetics are normal in Ttn ΔC1–2 mice, but that relaxation is slower. The slowed relaxation is, in part, attributable to an increased myofilament Ca2+ sensitivity and slower early Ca2+ reuptake. Cross-bridge dynamics showed that cross-bridge kinetics are normal but that the number of force-generating cross-bridges is reduced. In vivo sarcomere length (SL) measurements revealed that in Ttn ΔC1–2 mice the operating SL range of the LV is shifted towards shorter lengths. This normalizes the apparent cell and LV diastolic stiffness but further reduces systolic force as systole occurs further down on the ascending limb of the force-SL relation. We propose that the reduced working SLs reflect titin's role in regulating diastolic stiffness by altering the number of sarcomeres in series. Overall, our study reveals that thick filament length regulation by titin's C-zone is critical for normal cardiac function. [Display omitted] • Deletion of titin's super-repeats C1 and C2 (Ttn ΔC1-2 mice ) results in shorter thick filaments and contractile dysfunction. • This contractile dysfunction is more pronounced than expected based on the reduced thick filament length per se. • Diastolic stress is expected to be increased in Ttn ΔC1-2 mice, but instead is unaltered. • These findings can be explained by the discovered shift in the operating sarcomere-length (SL) range of Ttn ΔC1-2 mice. • The shift in operating SL range towards the shorter lengths further depresses contractility but normalizes titin-based passive stress. • It appears that titin regulates passive stress at the detriment of contractile function. [ABSTRACT FROM AUTHOR]

Introduces the Connected Mathematics Project, a mathematics curriculum approach to algebra in middle schools in the United States. Provision of different concepts in algebra; Emphasis on functional relationships in contextual algebraic problems; Types of algebraic problems and solution methods; Significance of skill practice in algebra.

The article proposes that how strict length control by nebulin promotes high-speed shortening and that dual-regulation by nebulin/Lmod2 enhances contraction efficiency. It mentions that importance of regulating the thin-filament length in muscle controlling the number of myosin motors that generate power.

Titin is largely comprised of serially-linked immunoglobulin (Ig) and fibronectin type-III (Fn3) domains. Many of these domains are arranged in an 11 domain super-repeat pattern that is repeated 11 times, forming the so-named titin C-zone in the A-band region of the sarcomere. Each super-repeat is thought to provide binding sites for thick filament proteins, such as cMyBP-C (cardiac myosin-binding protein C). However, it remains to be established which of titin's 11 C-zone super-repeats anchor cMyBP-C as titin contains 11 super-repeats and cMyBP-C is found in 9 stripes only. To study the layout of titin's C-zone in relation to MyBP-C, immunolabeling studies were performed on mouse skinned myocardium with antibodies to titin and cMyBP-C, using both immuno-electron microscopy and super-resolution optical microscopy. Results indicate that cMyBP-C locates near the interface between titin's C-zone super-repeats. Studies on a mouse model in which two of titin's C-zone repeats have been genetically deleted support that the first Ig domain of a super-repeat is important for anchoring cMyBP-C but also Fn3 domains located at the end of the preceding repeat. Furthermore, not all super-repeat interfaces are equal as the interface between super-repeat 1 and 2 (close to titin's D-zone) does not contain cMyBP-C. Finally, titin's C-zone does not extend all the way to the bare zone but instead terminates at the level of the second myosin crown. This study enhances insights in the molecular layout of the C-zone of titin, its relation to cMyBP-C, and its possible roles in cardiomyopathies. Unlabelled Image • The layout of titin's C-zone in relation to MyBP-C is relevant to cardiomyopathies but is unknown. • Immuno-localization studies showed that cMyBP-C locates near the interface between titin super-repeats. • Interface titin domains that belong to two super-repeats are likely involved in anchoring cMyBP-C. • Not all super-repeat interfaces are equal: the interface between super-repeat 1 and 2 does not localize cMyBP-C. • This study enhances insights in the molecular layout of titin's C-zone and its relation to cMyBP-C. [ABSTRACT FROM AUTHOR]

The article reports on the effort of the National Council of Teachers of Mathematics (NCTM) to improve student learning of mathematics in the U.S. It states that since 1980s, NCTM has been focusing on the dual goals of identifying curriculum standards and aligning curriculum materials and assessments with the standards. This strategy was further promoted by the No Child Left Behind legislative mandate for states to adopt challenging academic content standards in mathematics, reading and science.