Miracle-dz/UniFAR-FTUs huggingface dataset:
The Obesity Prevention Initiative: A Statewide Effort to Improve Child Health in Wisconsin.

BACKGROUND/SIGNIFICANCE Obesity rates have increased dramatically, especially among children and disadvantaged populations. Obesity is a complex issue, creating a compelling need for prevention efforts in communities to move from single isolated programs to comprehensive multisystem interventions. To address these issues, we have established a childhood Obesity Prevention Initiative (Initiative) for Wisconsin. This Initiative seeks to test community change frameworks that can support multisystem interventions and provide data for local action as a means for influencing policies, systems, and environments that support individuals' healthy eating and physical activity. APPROACHES/AIMS The Initiative is comprised of three components: (1) infrastructure to support a statewide obesity prevention and health promotion network with state- and local-level public messaging and dissemination of evidence-based solutions (healthTIDE); (2) piloting a local, multisetting community-led intervention study in 2 Wisconsin counties; and (3) developing a geocoded statewide childhood obesity and fitness surveillance system. RELEVANCE This Initiative is using a new model that involves both coalition action and community organizing to align resources to achieve health improvement at local and state levels. We expect that it will help lead to the implementation of cohesive and sustainable policy, system, and environment health promotion and obesity prevention strategies in communities statewide, and it has the potential to help Wisconsin become a national model for multisetting community interventions to address obesity. Addressing individual-level health through population-level changes ultimately will result in reductions in the prevalence of childhood obesity, current and future health care costs, and chronic disease mortality.
Targeting CYP2J to reduce paclitaxel-induced peripheral neuropathic pain

Significance Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a severe side effect that affects up to 80% of patients during cancer treatment. Pharmacological treatment options are poor, as CIPNP differs mechanistically from other chronic pain states. Here, we describe a mechanism by which pronociceptive oxidized lipid mediators are generated by the cytochrome P450-epoxygenase CYP2J2 in sensory neurons during CIPNP. Blocking the synthesis of these oxidized lipids with telmisartan, which we identified as a potent CYP2J2 inhibitor in a large drug repurposing screen, caused a robust reduction of paclitaxel-induced pain in mice in vivo. We therefore consider targeting CYP2J2 with telmisartan as a treatment option for chemotherapy-induced peripheral neuropathic pain in patients. Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a severe dose- and therapy-limiting side effect of widely used cytostatics that is particularly difficult to treat. Here, we report increased expression of the cytochrome-P450-epoxygenase CYP2J6 and increased concentrations of its linoleic acid metabolite 9,10-EpOME (9,10-epoxy-12Z-octadecenoic acid) in dorsal root ganglia (DRGs) of paclitaxel-treated mice as a model of CIPNP. The lipid sensitizes TRPV1 ion channels in primary sensory neurons and causes increased frequency of spontaneous excitatory postsynaptic currents in spinal cord nociceptive neurons, increased CGRP release from sciatic nerves and DRGs, and a reduction in mechanical and thermal pain hypersensitivity. In a drug repurposing screen targeting CYP2J2, the human ortholog of murine CYP2J6, we identified telmisartan, a widely used angiotensin II receptor antagonist, as a potent inhibitor. In a translational approach, administration of telmisartan reduces EpOME concentrations in DRGs and in plasma and reverses mechanical hypersensitivity in paclitaxel-treated mice. We therefore suggest inhibition of CYP2J isoforms with telmisartan as a treatment option for paclitaxel-induced neuropathic pain.
Body ownership promotes visual awareness

The sense of ownership of one’s body is important for survival, e.g., in defending the body against a threat. However, in addition to affecting behavior, it also affects perception of the world. In the case of visuospatial perception, it has been shown that the sense of ownership causes external space to be perceptually scaled according to the size of the body. Here, we investigated the effect of ownership on another fundamental aspect of visual perception: visual awareness. In two binocular rivalry experiments, we manipulated the sense of ownership of a stranger’s hand through visuotactile stimulation while that hand was one of the rival stimuli. The results show that ownership, but not mere visuotactile stimulation, increases the dominance of the hand percept. This effect is due to a combination of longer perceptual dominance durations and shorter suppression durations. Together, these results suggest that the sense of body ownership promotes visual awareness.
Forecasting Cyber Attacks with Imbalanced Data Sets and Different Time Granularities

If cyber incidents are predicted a reasonable amount of time before they occur, defensive actions to prevent their destructive effects could be planned. Unfortunately, most of the time we do not have enough observables of the malicious activities before they are already under way. Therefore, this work suggests to use unconventional signals extracted from various data sources with different time granularities to predict cyber incidents for target entities. A Bayesian network is used to predict cyber attacks where the unconventional signals are used as indicative random variables. This work also develops a novel minority class over sampling technique to improve cyber attack prediction on imbalanced data sets. The results show that depending on the selected time granularity, the unconventional signals are able to predict cyber attacks for the anonimyzed target organization even though the signals are not explicitly related to that organization. Furthermore, the minority over sampling approach developed achieves better performance compared to the existing filtering techniques in the literature.
Strategic Asset Allocation with Arbitrage-Free Bond Market using Dynamic Programming

Recently, Campbell and Viceira (2002) have introduced an intertemporal framework for asset allocation problem where the interest rate and the asset price dynamics are varying with the time. This paper follows up their work and try to explain the asset allocation puzzle of Canner, Mankiw and Weil(1997). We consider the bond prices systematically by integrating the no-arbitrage bond pricing models in the intertemporal framework. We employ the method of Dynamic Programming to solve the intertemporal consumption and portfolio decisions numerically because usually this intertemporal decision problems cannot be solved analytically. The numerical example considers the Vasicek bond price and the Markowitz stock price. Various properties of the consumption and portfolio decisions will be demonstrated in the numerical example. Our numerical results can explain the asset allocation puzzle. JEL Classification: G11(Portfolio Choice), C61(Optimization Techniques). Center of Empirical Macroeconomics(CEM) University Bielefeld, Germany School of Finance and Economics, University of Technology, Sydney, Australia Center of Empirical Macroeonomics(CEM), University Bielefeld and New School University, New York
Psychometric Evaluation of the Symptoms of Dementia Screener (SDS) in a Geriatric Primary Care Population

ABSTRACT Objectives: The Symptoms of Dementia Screener (SDS) is an 11-item scale developed to screen for cognitive impairment. We aim to evaluate the psychometric properties of the SDS for use in primary care. Methods: We analyzed data from 192 patients: 25 not impaired, 42 with mild cognitive impairment (MCI), and 125 with dementia. Cronbach’s reliability, convergent validity, and clinical utility were examined. The SDS was investigated at the item level using binary two-parameter model item response theory (IRT) techniques. Results: The SDS demonstrated good reliability (11 items; α = .74). We found negative correlations between SDS and the Mattis DRS-2 (r = −.523, p < .01). Receiver operating characteristic (ROC) curves demonstrated acceptable clinical utility for detecting MCI and dementia with sensitivities and specificities of 83% and 52% for MCI; 78.4% and 84% for dementia, and 91% and 52% for any impairment. IRT analyses revealed 10 out of 11 items were moderately to very highly related to underlying latent factors of impairment. Conclusions: The SDS demonstrates good psychometric properties and is useful for detecting cognitive impairment in primary care settings. Clinical Implications: The SDS is an effective screening tool that does not require special training for its use in primary care. A positive screen indicates a need for further cognitive testing.
N-terminal Sumoylation of Centromeric Histone H3 Variant Cse4 Regulates Its Proteolysis To Prevent Mislocalization to Non-centromeric Chromatin

Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4. In this study, we have identified lysine 65 (K65) in Cse4 as a site that regulates sumoylation and ubiquitin-mediated proteolysis of Cse4 by Slx5. Strains expressing cse4 K65R exhibit reduced levels of sumoylated and ubiquitinated Cse4 in vivo. Furthermore, co-immunoprecipitation experiments reveal reduced interaction of cse4 K65R with Slx5, leading to increased stability and mislocalization of cse4 K65R under normal physiological conditions. Based on the increased stability of cse4 K65R in psh1∆ strains but not in slx5∆ strains, we conclude that Slx5 targets sumoylated Cse4 K65 for ubiquitination-mediated proteolysis independent of Psh1. In summary, we have identified and characterized the physiological role of Cse4 K65 in sumoylation, ubiquitin-mediated proteolysis, and localization of Cse4 for genome stability.
Exocytosis is not involved in activation of Cl- secretion via CFTR in Calu-3 airway epithelial cells.

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl-channel, which mediates transepithelial Cl- transport in a variety of epithelia, including airway, intestine, pancreas, and sweat duct. In some but not all epithelial cells, cAMP stimulates Cl- secretion in part by increasing the number of CFTR Cl- channels in the apical plasma membrane. Because the mechanism whereby cAMP stimulates CFTR Cl- secretion is cell-type specific, our goal was to determine whether cAMP elevates CFTR-mediated Cl- secretion across serous airway epithelial cells by stimulating the insertion of CFTR Cl- channels from an intracellular pool into the apical plasma membrane. To this end we studied Calu-3 cells, a human airway cell line with a serous cell phenotype. Serous cells in human airways, such as Calu-3 cells, express high levels of CFTR, secrete antibiotic-rich fluid, and play a critical role in airway function. Moreover, dysregulation of CFTR-mediated Cl- secretion in serous cells is thought to contribute to the pathophysiology of cystic fibrosis lung disease. We report that cAMP activation of CFTR-mediated Cl- secretion across human serous cells involves stimulation of CFTR channels present in the apical plasma membrane and does not involve the recruitment of CFTR from an intracellular pool to the apical plasma membrane.
Surface chemistry mediated assembly of polymer-grafted nanorods in solution and polymer matrices

In the dissertation, I investigate ways to assemble nanorods, typically made of gold, in solution and polymer matrices by controlling surface chemistry. Gold nanorods were anisotropically functionalized with polymer on the side and alkane dithiol on the end causing the gold nanorods to spontaneously assemble in solution. The assembly could be tuned by controlling the incubation time which affected the solution absorbance due to plasmon coupling. Linked gold nanorods were cast in polymer thin films and their optical properties were imparted to the film. This anisotropic functionalization method was utilized to placed DNA or peptides on the ends of the gold nanorods allowing for reversibly assembly. In the case of DNA, assembly was reversed upon heating and could be tuned by controlling the concentration of the complimentary DNA strand. In the case of the peptide, assembly was triggered by the presence of Zn2+ ions and could be reversed by adding in a chelater. Anisotropic modification of the nanorods could also be used to assemble organic semiconductors around the nanorods at specific facets. Here, organic semiconductors rhodamine-B, 5(6)-carboxyfluorescein, and cyanine-3 were assembled onto the surface of gold nanorods. By tuning the surface chemistry the organic semiconductors would assemble around the nanorods in different ways which resulted in unique optical properties. The dispersion of PMMA-grafted mesoscopic iron-oxide rods in polymer matrices was studied by varying the PMMA brush molecular weight (N) polymer matrix molecular weight (P), and polymer matrix type. Here, we found that the ratio of P/N and matrix type had little effect on dispersion of iron-oxide mesorods. N was found to be the main factor that determined dispersion, which is attributed to the large size of the mesorods. Long PS and short PMMA brushes were grafted to gold nanorod surfaces and the dispersion of this system in PS and PMMA was investigated by controlling matrix molecular weight. We found that the gold nanorods would disperse in PS matrices 24 times larger than the grafted brush, while in PMMA matrices the nanorods would aggregate. SCFT calculations revealed that the good dispersion is most likely due to the collapse of the short PMMA brush and the enthalpic penalty for the collapse of the PS brush onto the PMMA brush. Finally, PS-grafted gold nanorods were assembled in liquid crystals. Assembly was tuned by controlling temperature and liquid crystal defect structure in the presence of micropillar arrays. The assembly of the nanorods resulted in changes in characteristic absorbance peaks of over 100 nm. From these studies, we are able to predict and control the assembly of nanorods in both solution and polymer matrices allowing us to fine-tune optical properties. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Chemical and Biomolecular Engineering First Advisor Russell J. Composto This dissertation is available at ScholarlyCommons: http://repository.upenn. edu/edissertations/1712
Cardiac diastolic function after recovery from pre-eclampsia

Summary Background Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. Aims The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. Methods This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. Results At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks’ gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11–10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Conclusion Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.
Enhanced photocatalytic activities on Bi_2O_2CO_3/ZnWO_4 nanocomposites

Bi_2O_2CO_3/ZnWO_4 composite photocatalysts have been successfully synthesized by a mixed calcination method after hydrothermal process. The catalysts were characterized by powder x-ray diffraction, scanning electron microscopy, transmission electron microscopy, high resolution transmission electron microscopy, x-ray photoelectron spectroscopy, and UV-vis diffuse reflectance spectrum. The results showed that the hierarchical Bi_2O_2CO_3/ZnWO_4 nanocomposites were obtained by mixed grinding calcination method and Bi_2O_2CO_3 nanospheres grow on the primary ZnWO_4 particles. The Bi_2O_2CO_3/ZnWO_4 composites exhibit higher photocatalytic activities compared to pure ZnWO_4 and Bi_2O_2CO_3 particles under UV light irradiation. Furthermore, the excellent photocatalytic efficiency of the Bi_2O_2CO_3/ZnWO_4 composite was deduced closely related to Bi_2O_2CO_3/ZnWO_4 heterojunctions whose presence is generally regarded to be a favorable factor for the separation of photogenerated electrons and holes.
Filopodia formation and endosome clustering induced by mutant plus-end–directed myosin VI

Significance How the mechanical properties of myosin motors relate to their functions in cells is poorly understood. Myosin VI (MYO6) is the only myosin that moves to the minus end of actin filaments, but the cellular requirement of this reverse movement is unknown. To investigate this question, we generated a mechanical mutant of MYO6, MYO6+, which moves to the plus end of actin filaments. This mutant causes clustering of signaling endosomes coupled to reorganization of cortical actin filaments into elongated filopodia. These two phenotypes depend on the multimerization of MYO6+ on the endosomal membrane induced by binding to lipids and adaptor proteins. Our results highlight the importance of endosomes for myosin-dependent regulation of cortical actin filaments in mammalian cells. Myosin VI (MYO6) is the only myosin known to move toward the minus end of actin filaments. It has roles in numerous cellular processes, including maintenance of stereocilia structure, endocytosis, and autophagosome maturation. However, the functional necessity of minus-end–directed movement along actin is unclear as the underlying architecture of the local actin network is often unknown. To address this question, we engineered a mutant of MYO6, MYO6+, which undergoes plus-end–directed movement while retaining physiological cargo interactions in the tail. Expression of this mutant motor in HeLa cells led to a dramatic reorganization of cortical actin filaments and the formation of actin-rich filopodia. MYO6 is present on peripheral adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) signaling endosomes and MYO6+ expression causes a dramatic relocalization and clustering of this endocytic compartment in the cell cortex. MYO6+ and its adaptor GAIP interacting protein, C terminus (GIPC) accumulate at the tips of these filopodia, while APPL1 endosomes accumulate at the base. A combination of MYO6+ mutagenesis and siRNA-mediated depletion of MYO6 binding partners demonstrates that motor activity and binding to endosomal membranes mediated by GIPC and PI(4,5)P2 are crucial for filopodia formation. A similar reorganization of actin is induced by a constitutive dimer of MYO6+, indicating that multimerization of MYO6 on endosomes through binding to GIPC is required for this cellular activity and regulation of actin network structure. This unique engineered MYO6+ offers insights into both filopodia formation and MYO6 motor function at endosomes and at the plasma membrane.
Identification of Unequally Represented Founder Viruses Among Tissues in Very Early SIV Rectal Transmission

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission. We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses was unequally represented in different tissues. This cluster of rare T/F viruses phylogenetically related to the non-dominant SIV variants in the inoculum and was not detected in any rectum tissues, but could be identified in the descending colon, jejunum, spleen, or plasma. In 2 out of 6 macaques, identical SIVmac251 variants belonging to this cluster were detected simultaneously in descending colon/jejunum and the inoculum. We also demonstrated that the average CG dinucleotide frequency of these rare T/F viruses found in tissues, as well as non-dominant variants in the inoculum, was significantly higher than the dominant T/F viruses in tissues and the inoculum. Collectively, these findings suggest that descending colon/jejunum might be more susceptible than rectum to SIV in the very early phase of infection. And host CG suppression, which was previously shown to inhibit HIV replication in vitro, may also contribute to the bottleneck selection during in vivo transmission.
Functional MRI examination of empathy for pain in people with schizophrenia reveals abnormal activation related to cognitive perspective-taking but typical activation linked to affective sharing

Background Schizophrenia is associated with important disturbances in empathy that are related to everyday functioning. Empathy is classically defined as including affective (sharing others’ emotions) and cognitive (taking others’ cognitive perspectives) processes. In healthy individuals, studies on empathy for pain revealed specific brain systems associated with these sets of processes, notably the anterior middle cingulate (aMCC) and anterior insula (AI) for affective sharing and the bilateral temporoparietal junction (TPJ) for the cognitive processes, but the integrity of these systems in patients with schizophrenia remains uncertain. Methods Patients with schizophrenia and healthy controls performed a pain empathy task while undergoing fMRI scanning. Participants observed pictures of hands in either painful or nonpainful situations and rated the level of pain while imagining either themselves (self) or an unknown person (other) in these situations. Results We included 27 patients with schizophrenia and 21 healthy controls in our analyses. For the pain versus no pain contrast, patients showed overall typical activation patterns in the aMCC and AI, with only a small part of the aMCC showing reduced activation compared with controls. For the other versus self contrast, patients showed an abnormal modulation of activation in the TPJ bilaterally (extending to the posterior superior temporal sulcus, referred to as the TPJ/pSTS). Limitations The design included an unnecessary manipulation of the visual perspective that reduced the number of trials for analysis. The sample size may not account for the heterogeneity of schizophrenia. Conclusion People with schizophrenia showed relatively intact brain activation when observing others’ pain, but showed abnormalities when asked to take the cognitive perspectives of others.