Publications

<p>Western blotting analysis of COMMED1, Skp2, p21, and α-Clusterin protein expression in vehicle control and DSF/CuCl2 treated 22Rv1-DR xenograft tumors.</p>

The performance of the code generated by a compiler depends on the order in which the optimization passes are applied. In high-level synthesis, the quality of the generated circuit relates directly to the code generated by the front-end compiler. Choosing a good order-often referred to as the phase-ordering problem-is an NP-hard problem. In this paper, we evaluate a new technique to address the phase-ordering problem: deep reinforcement learning. We implement a framework in the context of the LLVM compiler to optimize the ordering for HLS programs and compare the performance of deep reinforcement learning to state-of-the-art algorithms that address the phase-ordering problem. Overall, our framework runs one to two orders of magnitude faster than these algorithms, and achieves a 16% improvement in circuit performance over the -O3 compiler flag.

We introduce the $\ell_0\ell_2$-norm regularization and hierarchy constraints into linear regression for the construction of cluster expansion to describe configurational disorder in materials. The approach is implemented through mixed integer quadratic programming (MIQP). The $\ell_2$-norm regularization is used to suppress intrinsic data noise, while $\ell_0$-norm is used to penalize the number of non-zero elements in the solution. The hierarchy relation between clusters imposes relevant physics and is naturally included by the MIQP paradigm. As such, sparseness and cluster hierarchy can be well optimized to obtain a robust, converged, and effective cluster interactions with improved physical meaning. We demonstrate the effectiveness of $\ell_0\ell_2$-norm regularization in two high-component disordered rocksalt cathode material systems, where we compare the cross-validation and convergence speed, reproduction of phase diagrams, voltage profiles, and Li-occupancy energies with those of the conventional $\ell_1$-norm regularized cluster expansion model.

Abstract C(sp 3 )−Cl bonds are present in numerous biologically active small molecules, and an ideal route for their preparation is by the chlorination of a C(sp 3 )−H bond. However, most current methods for the chlorination of C(sp 3 )−H bonds are insufficiently site selective and tolerant of functional groups to be applicable to the late‐stage functionalization of complex molecules. We report a method for the highly selective chlorination of tertiary and benzylic C(sp 3 )−H bonds to produce the corresponding chlorides, generally in high yields. The reaction occurs with a mixture of an azidoiodinane, which generates a selective H‐atom abstractor under mild conditions, and a readily‐accessible and inexpensive copper(II) chloride complex, which efficiently transfers a chlorine atom. The reaction's exceptional functional group tolerance is demonstrated by the chlorination of >30 diversely functionalized substrates and the late‐stage chlorination of a dozen derivatives of natural products and active pharmaceutical ingredients.

Summary Using data from 1721 participants in a community‐based randomized control trial of digital cognitive behavioural therapy for insomnia compared with patient education, we employed linear mixed modelling analyses to examine whether chronotype moderated the benefits of digital cognitive behavioural therapy for insomnia on self‐reported levels of insomnia severity, fatigue and psychological distress. Baseline self‐ratings on the reduced version of the Horne–Östberg Morningness–Eveningness Questionnaire were used to categorize the sample into three chronotypes: morning type ( n = 345; 20%); intermediate type ( n = 843; 49%); and evening type ( n = 524; 30%). Insomnia Severity Index, Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression Scale were assessed pre‐ and post‐intervention (9 weeks). For individuals with self‐reported morning or intermediate chronotypes, digital cognitive behavioural therapy for insomnia was superior to patient education on all ratings (Insomnia Severity Index, Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression Scale) at follow‐up ( p ‐values ≤ 0.05). For individuals with self‐reported evening chronotype, digital cognitive behavioural therapy for insomnia was superior to patient education for Insomnia Severity Index and Chalder Fatigue Questionnaire, but not on the Hospital Anxiety and Depression Scale ( p = 0.139). There were significant differences in the treatment effects between the three chronotypes on the Insomnia Severity Index ( p = 0.023) estimated difference between evening and morning type of −1.70, 95% confidence interval: −2.96 to −0.45, p = 0.008, and estimated difference between evening and intermediate type −1.53, 95% confidence interval: −3.04 to −0.03, p = 0.046. There were no significant differences in the treatment effects between the three chronotypes on the Chalder Fatigue Questionnaire ( p = 0.488) or the Hospital Anxiety and Depression Scale ( p = 0.536). We conclude that self‐reported chronotype moderates the effects of digital cognitive behavioural therapy for insomnia on insomnia severity, but not on psychological distress or fatigue.

Insulin resistance is necessary but not sufficient for the development of type 2 diabetes. Diabetes results when pancreatic beta-cells fail to compensate for insulin resistance by increasing insulin production through an expansion of beta-cell mass or increased insulin secretion. Communication between insulin target tissues and beta-cells may initiate this compensatory response. Correlated changes in gene expression between tissues can provide evidence for such intercellular communication. We profiled gene expression in six tissues of mice from an obesity-induced diabetes-resistant and a diabetes-susceptible strain before and after the onset of diabetes. We studied the correlation structure of mRNA abundance and identified 105 co-expression gene modules. We provide an interactive gene network model showing the correlation structure between the expression modules within and among the six tissues. This resource also provides a searchable database of gene expression profiles for all genes in six tissues in lean and obese diabetes-resistant and diabetes-susceptible mice, at 4 and 10 wk of age. A cell cycle regulatory module in islets predicts diabetes susceptibility. The module predicts islet replication; we found a strong correlation between 2 H 2 O incorporation into islet DNA in vivo and the expression pattern of the cell cycle module. This pattern is highly correlated with that of several individual genes in insulin target tissues, including Igf2 , which has been shown to promote beta-cell proliferation, suggesting that these genes may provide a link between insulin resistance and beta-cell proliferation.

Health in My Community:Conducting and Evaluating PhotoVoice as a Tool to Promote Environmental Health and Leadership Among Latino/a Youth Daniel Santiago Madrigal, Alicia Salvatore, Gardenia Casillas, Crystal Casillas, Irene Vera, Brenda Eskenazi, and Meredith Minkler What Is the Purpose of This Study? • Evaluate the use of PhotoVoice in an environmental health leadership program with a group of Latino adolescents from an agricultural area. What Is the Problem? • Latinos and low-income communities bear a disproportionate burden of exposure to environmental contaminants that can lead to health disparities. Residents of the Salinas community are exposed to chemicals used in pesticides because of large scale agricultural production in the area. • PhotoVoice has been used in a diverse array of communities; however, it has not been extensively tested with adolescents from agricultural communities. • Few tools exist to help adolescents learn about environmental health hazards and to prepare them to take action to create healthier environments. What Are the Findings? • Sixteen youth participated in the project and took a total of 712 photographs. The key themes that emerged from their pictures and discussions were: poor access to affordable, healthy foods; limited access to safe spaces for physical activity; ease of access to tobacco products; and poor working conditions for farmworkers. Positive themes or assets included committed individuals and community organizations working for a stronger community and plenty of open spaces in surrounding areas (see photos and summaries at www.cerch.org.com/chamacosycc). • Youth participants shared their photos and narrative summaries with members of their community at the main public library, an event at the local health department, on youth radio, and on public access television. • The youth coordinated two action projects to address the issues identified through PhotoVoice. The first was a 5k Run/Walk in collaboration with another local health organization to bring attention to the lack of safe space for physical activity and provide an opportunity for the community to come together and exercise. Over 800 community members participated in the event. For the second action project, youth members took initial steps toward bringing a recycling program to one of the local high schools. • Pre- and post- tests revealed that after the PhotoVoice project, youth participants were significantly more likely to report improvements in leadership, teamwork, and participatory behavior. No changes were observed on perceived ability to make a real difference in improving their city, or being able to work with other students on an issue that affects youth their city. Measurement timing issues may have resulted in under-estimation of changes observed. Exit interviews with participants showed more positive perceived impacts in ability to help make positive change and other areas than had the pretests and posttests. [End Page 267] • The biggest challenge of the project involved practical issues including: transportation to the meetings, conflicts with other activities that the youth members were involved in such as academics, sports, and extracurricular activities, and maintaining a supportive group environment. Who Should Care Most? • Communities and researchers who are interested in engaging youth in environmental health research and seek to strengthen their findings with perspectives from adolescent members of their communities. • Youth development programs which work with Latino youth from agricultural areas. Recommendation for Action • PhotoVoice should be used in agricultural communities interested in building environmental health leadership in Latino youth. The focus of the work with youth should be to create a program that is engaging, informative, builds leadership, and is centered on action. • New programs using this approach should anticipate and work to address common problems that may occur in areas including transportation, conflicting youth priorities, and effective group dynamics. • New programs should also attempt to include policy makers from the beginning to ensure the successful implementation of any policy- related goals that may arise from the PhotoVoice process. [End Page 268] Daniel Santiago Madrigal University of California, Berkeley, School of Public Health Alicia Salvatore Stanford University School of Medicine Gardenia Casillas University of California, Berkeley, School of Public Health Crystal Casillas Salinas, CA Irene Vera Salinas, CA Brenda Eskenazi University of California, Berkeley, School of Public Health Meredith Minkler University of California, Berkeley, School of Public Health Copyright © 2014 The Johns Hopkins University Press

Formate is a major reactive carbon species in one-carbon metabolism, where it serves as an endogenous precursor for amino acid and nucleic acid biosynthesis and a cellular source of NAD(P)H. On the other hand, aberrant elevations in cellular formate are connected to progression of serious diseases, including cancer and Alzheimer’s disease. Traditional methods for formate detection in biological environments often rely on sample destruction and/or extensive processing, resulting in a loss of spatiotemporal information. To help address these limitations, here we present the design, synthesis, and biological evaluation of a first-generation activity-based sensing system for live-cell formate imaging that relies on iridium transfer hydrogenation catalysis. Formate facilitates an aldehyde-to alcohol conversion on various fluorophore scaffolds to enable fluorescence detection of this one-carbon unit, including through a two-color ratiometric response with internal calibration. The resulting two-component probe system can detect changes in formate levels in living cells with high selectivity over potentially competing biological analytes. Moreover, this activity-based sensing system can visualize changes in endogenous formate fluxes through alterations of one-carbon pathways in cell-based models of human colon cancer, presaging the potential utility of this chemical approach to probe the continuum between one-carbon metabolism and signaling in cancer and other diseases.

ABSTRACT Progressive increases in the precision of the Hubble-constant measurement via Cepheid-calibrated Type Ia supernovae (SNe Ia) have shown a discrepancy of ∼4.4σ with the current value inferred from Planck satellite measurements of the cosmic microwave background radiation and the standard $\Lambda $cold dark matter (ΛCDM) cosmological model. This disagreement does not appear to be due to known systematic errors and may therefore be hinting at new fundamental physics. Although all of the current techniques have their own merits, further improvement in constraining the Hubble constant requires the development of as many independent methods as possible. In this work, we use SNe II as standardisable candles to obtain an independent measurement of the Hubble constant. Using seven SNe II with host-galaxy distances measured from Cepheid variables or the tip of the red giant branch, we derive H$_0= 75.8^{+5.2}_{-4.9}$ km s−1 Mpc−1 (statistical errors only). Our value favours that obtained from the conventional distance ladder (Cepheids + SNe Ia) and exhibits a difference of 8.4 km s−1 Mpc−1 from the Planck + ΛCDM value. Adding an estimate of the systematic errors (2.8 km s−1 Mpc−1) changes the ∼1.7σ discrepancy with Planck +ΛCDM to ∼1.4σ. Including the systematic errors and performing a bootstrap simulation, we confirm that the local H0 value exceeds the value from the early Universe with a confidence level of 95 per cent. As in this work, we only exchange SNe II for SNe Ia to measure extragalactic distances, we demonstrate that there is no evidence that SNe Ia are the source of the H0 tension.

One of the major challenges facing the rapidly growing field of two-dimensional (2D) transition metal dichalcogenides (TMDCs) is the development of growth techniques to enable large-area synthesis of high-quality materials. Chemical vapor deposition (CVD) is one of the leading techniques for the synthesis of TMDCs; however, the quality of the material produced is limited by defects formed during the growth process. A very useful nondestructive technique that can be utilized to probe defects in semiconductors is the room-temperature photoluminescence (PL) quantum yield (QY). It was recently demonstrated that a PL QY near 100% can be obtained in MoS2 and WS2 monolayers prepared by micromechanical exfoliation by treating samples with an organic superacid: bis(trifluoromethane)sulfonimide (TFSI). Here we have performed a thorough exploration of this chemical treatment on CVD-grown MoS2 samples. We find that the as-grown monolayers must be transferred to a secondary substrate, which releases strain, to obtain high QY by TFSI treatment. Furthermore, we find that the sulfur precursor temperature during synthesis of the MoS2 plays a critical role in the effectiveness of the treatment. By satisfying the aforementioned conditions we show that the PL QY of CVD-grown monolayers can be improved from ∼0.1% in the as-grown case to ∼30% after treatment, with enhancement factors ranging from 100 to 1500× depending on the initial monolayer quality. We also found that after TFSI treatment the PL emission from MoS2 films was visible by eye despite the low absorption (5-10%). The discovery of an effective passivation strategy will speed the development of scalable high-performance optoelectronic and electronic devices based on MoS2.