Transportation policy for campus climate action planning: Process and policy implications

This article discusses the innovative methods used to complete the transportation components of Cal Poly’s Climate Action Plan (CAP). The campus\u27s CAP was completed by a BSCRP studio during the fall and winter quarters (2015-2016AY) in collaboration with Facilities Planning and Capital Projects. Professors William Riggs and Adrienne Greve (instructors for the studio along with Chris Clark) developed the methods discussed here, and C. Kai Lord-Farmer was the graduate assistant who assisted in completing the technical analysis

Redesigning a Street Corridor in San Clemente, CA: South El Camino Real Urban Design Concept Plan

The South El Camino Real Urban Design Concept Plan was developed by a first-year MCRP studio for the City of San Clemente, CA. The San Clemente community, the City planners and the City Council welcomed the students’ ideas for making the corridor appealing, economically attractive, and safer for pedestrians and bicyclists

Cal Poly Climate Action Plan

The Cal Poly Climate Action Plan (PolyCAP) is designed to achieve the California State University (CSU) Chancellor’s mandate to reduce greenhouse gas (GHG) emissions to 1990 levels by 2020 and 80% below 1990 levels by 2040 (CSU, 2014). California Polytechnic State University, San Luis Obispo (Cal Poly) Facility Management and Development (FM&D) and the City and Regional Planning (CRP) Senior Community Planning Laboratory developed the PolyCAP during the Fall 2015 and Winter 2016 quarters, with editing and refinement in subsequent quarters. The goal of the PolyCAP is to reduce Cal Poly’s GHG emissions and to adapt the Campus to a changing climate. The PolyCAP aims to exceed the CSU mandate and achieve Net Zero GHG emissions by 2050, in accordance with Cal Poly’s signing of the Second Nature Climate Commitment. Cal Poly is updating its Master Plan to 2035, examining University academics, buildings, housing, transportation, agriculture, and more. The PolyCAP is intended to aid the Draft Master Plan Update to achieve its goal to be responsive to climate change. Many strategies of the PolyCAP can also be implemented as mitigation measures in the Draft Master Plan Update Environmental Impact Report (EIR)

Systems analysis of dynamic transcription factor activity identifies targets for treatment in Olaparib resistant cancer cells

The development of resistance to targeted therapeutics is a challenging issue for the treatment of cancer. Cancers that have mutations in BRCA, a DNA repair protein, have been treated with poly(ADP‐ribose) polymerase (PARP) inhibitors, which target a second DNA repair mechanism with the aim of inducing synthetic lethality. While these inhibitors have shown promise clinically, the development of resistance can limit their effectiveness as a therapy. This study investigated mechanisms of resistance in BRCA‐mutated cancer cells (HCC1937) to Olaparib (AZD2281) using TRACER, a technique for measuring dynamics of transcription factor (TF) activity in living cells. TF activity was monitored in the parental HCC1937 cell line and two distinct resistant cell lines, one with restored wild‐type BRCA1 and one with acquired resistance independent of BRCA1 for 48 h during treatment with Olaparib. Partial least squares discriminant analysis (PLSDA) was used to categorize the three cell types based on TF activity, and network analysis was used to investigate the mechanism of early response to Olaparib in the study cells. NOTCH signaling was identified as a common pathway linked to resistance in both Olaparib‐resistant cell types. Western blotting confirmed upregulation of NOTCH protein, and sensitivity to Olaparib was restored through co‐treatment with a gamma secretase inhibitor. The identification of NOTCH signaling as a common pathway contributing to PARP inhibitor resistance by TRACER indicates the efficacy of transcription factor dynamics in identifying targets for intervention in treatment‐resistant cancer and provides a new method for determining effective strategies for directed chemotherapy. Biotechnol. Bioeng. 2017;114: 2085–2095. © 2017 Wiley Periodicals, Inc.Dynamic cell response to therapy is dependent on the sensitivity of the cells to treatment. In this work, a transcriptional activity cell array (TRACER) was used to measure transcription factor activity dynamics in BRCA‐mutated breast cancer cells during treatment with Olaparib. The dynamic measurements were used to both identify sensitive and resistant cells as well as suggest therapy to resensitize resistant cells.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137743/1/bit26293_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137743/2/bit26293.pd

The prevalence and incidence of mental ill-health in adults with autism and intellectual disabilities

The prevalence, and incidence, of mental ill-health in adults with intellectual disabilities and autism were compared with the whole population with intellectual disabilities, and with controls, matched individually for age, gender, ability-level, and Down syndrome. Although the adults with autism had a higher point prevalence of problem behaviours compared with the whole adult population with intellectual disabilities, compared with individually matched controls there was no difference in prevalence, or incidence of either problem behaviours or other mental ill-health. Adults with autism who had problem behaviours were less likely to recover over a two-year period than were their matched controls. Apparent differences in rates of mental ill-health are accounted for by factors other than autism, including Down syndrome and ability level

Cortical interactions during the resolution of information processing demands in autism spectrum disorders

Introduction Our flexible and adaptive interactions with the environment are guided by our individual representation of the physical world, estimated through sensation and evaluation of available information against prior knowledge. When linking sensory evidence with higher-level expectations for action, the central nervous system (CNS) in typically developing (TD) individuals relies in part on distributed and interacting cortical regions to communicate neuronal signals flexibly across the brain. Increasing evidence suggests that the balance between levels of signal and noise during information processing may be disrupted in individuals with Autism Spectrum Disorders (ASD). Methods Participants with and without ASD performed a visuospatial interference task while undergoing functional Magnetic Resonance Imaging (fMRI). We empirically estimated parameters characterizing participants’ latencies and their subtle fluctuations (noise accumulation) over the 16-min scan. We modeled hemodynamic activation and used seed-based analyses of neural coupling to study dysfunction in interference-specific connectivity in a subset of ASD participants who were nonparametrically matched to TD participants on age, male-to-female ratio, and magnitude of movement during the scan. Results Stochastic patterns of response fluctuations reveal significantly higher noise-to-signal levels and a more random and noisy structure in ASD versus TD participants, and in particular ASD adults who have the greatest clinical autistic deficits. While individuals with ASD show an overall weaker modulation of interference-specific functional connectivity relative to TD individuals, in particular between the seeds of Anterior Cingulate Cortex (ACC) and Inferior Parietal Sulcus (IPS) and the rest of the brain, we found that in ASD, higher uncertainty during the task is linked to increased interference-specific coupling between bilateral anterior insula and prefrontal cortex. Conclusions Subtle and informative differences in the structure of experiencing information exist between ASD and TD individuals. Our findings reveal in ASD an atypical capacity to apply previously perceived information in a manner optimal for adaptive functioning, plausibly revealing suboptimal message-passing across the CNS

Social Networks and Friendships at School: Comparing Children With and Without ASD

Self, peer and teacher reports of social relationships were examined for 60 high-functioning children with ASD. Compared to a matched sample of typical children in the same classroom, children with ASD were more often on the periphery of their social networks, reported poorer quality friendships and had fewer reciprocal friendships. On the playground, children with ASD were mostly unengaged but playground engagement was not associated with peer, self, or teacher reports of social behavior. Twenty percent of children with ASD had a reciprocated friendship and also high social network status. Thus, while the majority of high functioning children with ASD struggle with peer relationships in general education classrooms, a small percentage of them appear to have social success

Achieving positive change for children? Reducing the length of child protection proceedings: lessons from England and Wales

Court decisions are required to remove children, compulsorily, from their families, and approve permanent care arrangements which restrict or terminate parents’ rights. The children involved are mostly young, have experienced serious abuse or neglect and may require permanent placement away from their parent(s) for their remaining childhoods. In England and Wales, justice to parents has dominated the rhetoric about these proceedings; this has resulted in lengthy proceedings, long periods of uncertainty for children and reduced placement options. In order to reduce delays, reforms in England and Wales have set a time limit for the completion of care proceedings. The Children and Families Act 2014 limits proceedings to 26 weeks; approximately 60% of care proceedings are now completed within this period. This article will discuss the impact of these reforms on decision-making for children, questioning whether they achieve both good decisions for children and justice for families. It uses the findings of an ESRC-funded study: ‘Establishing outcomes of care proceedings for children before and after care proceedings reform (2015–2018)’

Methodological approaches in application of synthetic lethality screening towards anticancer therapy

A promising direction in the development of selective less toxic cancer drugs is the usage of synthetic lethality concept. The availability of large-scale synthetic low-molecular-weight chemical libraries has allowed HTS for compounds synergistic lethal with defined human cancer aberrations in activated oncogenes or tumour suppressor genes. The search for synthetic lethal chemicals in human/mouse tumour cells is greatly aided by a prior knowledge of relevant signalling and DNA repair pathways, allowing for educated guesses on the preferred potential therapeutic targets. The recent generation of human/rodents genome-wide siRNAs, and shRNA-expressing libraries, should further advance this more focused approach to cancer drug discovery