cssi/SciSciGPT-SciSciNet huggingface dataset:
Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in myotonic dystrophy

Myotonic dystrophy type I (DM1) is an RNA-mediated disease caused by a non-coding CTG repeat expansion. A key feature of the RNA-mediated pathogenesis model for DM is the disrupted splicing of specific pre-mRNA targets. A link has been established between splicing regulation by CUG-BP1, a member of the CELF family of proteins, and DM1 pathogenesis. To determine whether increased CUG-BP1 function was sufficient to model DM, transgenic mice overexpressing CUG-BP1 (MCKCUG-BP1) in heart and skeletal muscle, two tissues affected in DM1, were generated. Histological and electron microscopic analyses of skeletal muscle reveal common pathological features with DM tissues: chains of central nuclei, degenerating fibers and centralized NADH reactivity. MCKCUG-BP1 mice have disrupted splicing of three CELF target pre-mRNAs, cardiac troponin T (Tnnt2), myotubularin-related 1 gene (Mtmr1) and the muscle-specific chloride channel (Clcn1), consistent with that observed in DM heart and skeletal muscle. The results are consistent with a mechanism for DM pathogenesis in which expanded repeats result in increased CUG-BP1 activity and/or other CELF family members and have trans-dominant effects on specific pre-mRNA targets.
Self-tuning of robot program primitives

Strategies used and parameter selection problems encountered in developing robot programs are addressed by describing an approach to self-tuning of robot program parameters. In this approach, the robot program incorporates control primitives with adjustable parameters and an associated cost function. A hybrid gradient-based and direct-search algorithm uses experimentally measured performance data to adjust the parameters to seek optimal performance and track system variations. Alternative control strategies which have first been optimized with the same cost function are then assessed in terms of their optimized behavior. It is demonstrated that the optimal control strategy for a particular task is a function not only of task geometry, but also of the desired performance. >
The effects of size, shape, and surface functional group of gold nanostructures on their adsorption and internalization by cells.

In this study, we examined the effects of size, shape, and surface chemistry of gold nanostructures on their uptake (including both adsorption and internalization) by SK-BR-3 breast cancer cells. We used both spherical and cubic Au nanostructures (nanospheres and nanocages, respectively) of two different sizes, and their surface was modified with poly(ethylene glycol) (PEG), antibody anti-HER2, or poly(allyamine hydrochloride) (PAA). Our results showed that the size of the Au nanostructures influenced their uptake by the cells in a similar way regardless of the surface chemistry, while the shape dependency could vary depending on the surface functional group. In addition, the cells preferred to take up the Au nanostructures covered by different surface groups in the following order: PAA>> anti-HER2> PEG. The fraction of Au nanostructures attached to the cell surface was also dependent on the aforementioned parameters.
Whac-a-mole: future trends in Chagas transmission and the importance of a global perspective on disease control

. Through the Southern Cone Initia-tive, Chagas disease was effectively ‘whac’d’ byintergovernmental partnerships supervised by thePan American Health Organization (PAHO),and transmission halted in Uruguay (1997),Chile (1999), and in most areas of Argentina,Paraguay and Bolivia, by eliminating the insectvectors and blood transfusion transmission.Called the silent killer, Chagas disease usuallydemonstrates mild symptoms during the initialweeks following infection (swelling at the site ofinfection, fever, malaise and lymphadenopathy),so diagnosis at this stage is rare. Most patientsprogress to the ‘silent’, sometimes decades-longasymptomatic period before 20–40% of infectedpeople advance to fatal heart disease and/ormegasyndrome. Around 80% of transmissionoccurs via insect vectors; parasites in the fecestypically gain access through the bite wound ormucous membranes. Transmission by bloodproducts and solid-organ transplantation, con-genitally and even by contaminated food or drinkalso occurs. Different strains of
The Cross-Linking of Cotton With Vinyl Monomers Using Radiation and Chemical Catalysis1

The work presented here is the result of a series of experiments attempting to cross-link cotton by using difunctional monomers having at least one vinyl group. Emphasis was placed on the delayed cure aspects of these monomers. Chemical reaction of the monomers was initiated both by ionizing radiation and by a conventional. chemical free-radical catalyst.
Bourgeois Vedānta: The Colonial Roots of Middle-class Hinduism

The quest to balance the material and the spiritual has a long history in the Hindu tradition, as it does in the West. While Hindus recognize desire to be a central human value, they also see it as a cause of human suffering. This tension persists within contemporary Hinduism, especially among an emergent middle class that seeks to balance spiritual fulfillment and worldly success. If we are to understand recent manifestations of Hinduism, we would do well to explore their roots in the colonial period. That is the goal of this essay, which explores the
One-loop divergences in the quantum theory of supergravity☆

Abstract Supergravity does not lead to a finite quantum theory of gravitation when coupled to the spin 1, 1 2 matter multiplet. The S-matrix of photon-photon scattering diverges; its divergences are proportional to the square of the photon energy-momentum tensor, in agreement with electro-magnetic duality and chiral invariance. The graviton self-energy corrections are divergent in pure supergravity as well as in the coupled Maxwell-Einstein system and satisfy their Ward identity because the supersymmetry ghost field is commuting. The photon-graviton vertex corrections diverge, as expected from the non-invariance of the action under local scale transformations, and satisfy the equivalence principle at the quantum level. The photon self-energy is divergent.
The TprK protein of Treponema pallidum is periplasmic and is not a target of opsonic antibody or protective immunity.

The finding that Treponema pallidum, the syphilis spirochete, contains 12 orthologs of the Treponema denticola outer membrane major sheath protein has engendered speculation that members of this T. pallidum repeat (Tpr) family may be similarly surface exposed. In this regard, the TprK protein was reported to be a target of opsonic antibody and protective immunity and subject to immunologically driven sequence variation. Despite these findings, results from our previous analyses of treponemal outer membranes in concert with computer-based predictions for TprK prompted us to examine the cellular location of this protein. TprK–alkaline phosphatase fusions expressed in Escherichia coli demonstrate that TprK contains a signal peptide. However, opsonophagocytosis assays failed to indicate surface exposure of TprK. Moreover, results from three independent methodologies, i.e., (a) indirect immunofluorescence analysis of agarose-encapsulated organisms, (b) proteinase K treatment of intact spirochetes, and (c) Triton X-114 phase partitioning of T. pallidum conclusively demonstrated that native TprK is entirely periplasmic. Consistent with this location, immunization with the recombinant protein failed to induce either protective immunity or select for TprK variants in the rabbit model of experimental syphilis. These findings challenge the notion that TprK will be a component of an efficacious syphilis vaccine.
Phosphorylation energy hypothesis : Open chemical systems and 'their biological functions

AbstractBiochemical systems and processes in living cells generally operate far from equilibrium. This review presents an overview of a statistical thermodynamic treatment for such systems, with examples from several key components in cellular signal transduction. Open-system nonequilibrium steady-state (NESS) models are introduced. The models account quantitatively for the energetics and thermodynamics in phosphorylation-dephosphorylation switches, GTPase timers, and specificity amplification through kinetic proofreading. The chemical energy derived from ATP and GTP hydrolysis establishes the NESS of a cell and makes the cell—a mesoscopic–biochemical reaction system that consists of a collection of thermally driven fluctuating macromolecules—a genetically programmed chemical machine.
Response to “Emergence in Sociology”:

Jens Greve has accurately summarized nonreductive individualism (NRI) and has made an important contribution to an ongoing discussion concerning individualism, reductionism, and emergentism. Greve’s primary criticism is of my account of downward causation, and he cites Kim’s critique of Fodor by analogy. I argue that my original paper already addressed Kim’s critique, by drawing on other philosophers of mind that Greve does not engage with, to make an argument for downward causation based on wild disjunction. Further, I argue that Greve does not successfully make the case that the issue of the autonomy of the mental level is distinct from the autonomy of the social level. As empirical examples of irreducible emergent group properties, I cite studies of improvisational theater dialogues, and studies of social networks.
Comparison of manufacturing performance of three team structures in semiconductor plants

Manufacturing programs aimed at improving performance often feature employee teams that address production problems at the shop-floor level. According to cognitive models of participation, performance under such programs is improved via the better utilization of skills and knowledge that occurs as employees are allowed greater decision making in their tasks. The authors examine the cognitive-model premise in a high-technology industry where improvement-team programs are on the rise. The study three types of improvement-team programs among a sample of eight manufacturing sites. The programs feature continuous improvement teams (CITs), quality circles (QCs) or self-directed work teams (SDWTs) and vary in the amount of decision-making power, skill attainment via training and skill use granted to employees. A quantitative analysis of performance reveals that CIT programs were associated with the highest direct and indirect productivity, two metrics that were available for each firm. QC and SDWT programs should not be dismissed, however, as they may lead to improvements in quality metrics, as the authors note in suggestions for future research. Qualitative data gathered in site visits suggest that poor implementation and failure to integrate production programs with engineering departments are two factors that inhibit program success.
On model-based MR spectroscopic imaging

In this paper, we analyze the model-based reconstruction framework in MR spectroscopic imaging and derive an exact expression for the reconstruction error. Based on the insight provided by the analysis, we propose two modifications: (a) we introduce a new echo-planar imaging sequence to acquire more Fourier samples in the same scan duration, since increasing the number of Fourier samples will decrease the bias in the reconstructions. We then use the model-based framework to effectively compensate for the corresponding loss in signal to noise ratio/measurement, (b) we observe that model misfit can affect the reconstructions in constrained imaging much more seriously than standard Fourier reconstruction. We propose a data adaptive basis selection procedure to reduce the misfit, without significantly increasing the noise variance. Both these improvements together enable high-resolution reconstructions that are more robust and with fewer artifacts as compared to reduced encoding, without increasing the scan time.
Route Prediction from Trip Observations

This paper develops and tests algorithms for predicting the end-to-end route of a vehicle based on GPS observations of the vehicle’s past trips. We show that a large portion of a typical driver’s trips are repeated. Our algorithms exploit this fact for prediction by matching the first part of a driver’s current trip with one of the set of previously observed trips. Rather than predicting upcoming road segments, our focus is on making long term predictions of the route. We evaluate our algorithms using a large corpus of real world GPS driving data acquired from observing over 250 drivers for an average of 15.1 days per subject. Our results show how often and how accurately we can predict a driver’s route as a function of the distance already driven.
Prosody based audiovisual coanalysis for coverbal gesture recognition

Despite recent advances in vision-based gesture recognition, its applications remain largely limited to artificially defined and well-articulated gesture signs used for human-computer interaction. A key reason for this is the low recognition rates for "natural" gesticulation. Previous attempts of using speech cues to reduce error-proneness of visual classification have been mostly limited to keyword-gesture coanalysis. Such scheme inherits complexity and delays associated with natural language processing. This paper offers a novel "signal-level" perspective, where prosodic manifestations in speech and hand kinematics are considered as a basis for coanalyzing loosely coupled modalities. We present a computational framework for improving continuous gesture recognition based on two phenomena that capture voluntary (coarticulation) and involuntary (physiological) contributions of prosodic synchronization. Physiological constraints, manifested as signal interruptions during multimodal production, are exploited in an audiovisual feature integration framework using hidden Markov models. Coarticulation is analyzed using a Bayesian network of naive classifiers to explore alignment of intonationally prominent speech segments and hand kinematics. The efficacy of the proposed approach was demonstrated on a multimodal corpus created from the Weather Channel broadcast. Both schemas were found to contribute uniquely by reducing different error types, which subsequently improves the performance of continuous gesture recognition.
Intrahepatic IL-10 Maintains NKG2A+Ly49− Liver NK Cells in a Functionally Hyporesponsive State

The tolerogenic nature of the liver allows daily exposure to gut-derived foreign Ags without causing inflammation, but it may facilitate persistent infection in the liver. NK cells play a central role in innate immunity, as well as in shaping the adaptive immune response. We hypothesized that the naive mouse liver maintains intrahepatic NK cells in a functionally hyporesponsive state. Compared with splenic NK cells, liver NK cells displayed a dampened IFN-γ response to IL-12/IL-18 stimulation. Importantly, the liver contains a significant population of functionally hyporesponsive NK cells that express high levels of the inhibitory receptor NKG2A and lack expression of MHC class I-binding Ly49 receptors. Adoptively transferred splenic NK cells that migrate to the liver displayed phenotypic and functional changes, suggesting that the liver environment modifies NK cell receptor expression and functional responsiveness. Notably, IL-10 is present at high levels within the liver, and in vivo blockade of IL-10R resulted in a decreased percentage of intrahepatic NKG2A+Ly49− NK cells. These data suggest that the liver environment regulates NK cell receptor expression and that IL-10 contributes to the regulation of liver NK cells, in part, by maintaining a greater percentage of the hyporesponsive NKG2A+Ly49− NK cells in the liver.
Identification of Bona Fide Farmers

Georgia's General Assembly considered differential assessment legislation in 1976, but rejected the final proposals on the last day of the session. Last minute efforts to develop an acceptable legislative proposal concerned the issue of what farmland should be eligible for differential assessment. One proposal considered a single criterion—the proportion of income derived from farming. This proposal stated that operators who derive more than 50 percent of their income from farming should be considered bona fide farmers and their land eligible for differential assessment. While all landowners qualifying as bona fide farm operators would benefit from a reduction in their tax bills, others would probably pay higher taxes than without differential assessment legislation. Consequently, it is important to evaluate criteria used to designate bona fide farm operators.
Leaf gas exchange responses of 13 prairie grassland species to elevated CO2 and increased nitrogen supply

Summary • Leaf gas exchange responses to elevated CO 2 and N are presented for 13 perennial species, representing four functional groups: C 3 grasses, C 4 grasses, legumes, and nonleguminous forbs. Understanding how CO 2 and N effects interact is important to predict plant community response to global change. • Plants were field-grown in monoculture under current ambient and elevated (560 μ mol mol - 1 ) CO 2 concentrations (free-air CO 2 enrichment), in combination with soil N treatments, for two growing seasons. • All species, regardless of functional group, showed pronounced photosynthetic acclimation to elevated CO 2 , resulting in minimal stimulation of photosynthesis ( A ) averaging +15% in C 3 grasses, +8% in forbs, + 7% in legumes and - 2% in C 4 grasses. The effects of CO 2 and soil N supply did not interact for any leaf traits measured. Elevated CO 2 consistently decreased stomatal conductance ( g s ) leading to 40% increase in A / g s . • This substantial acclimation of photosynthesis was greater in magnitude than in most field studies, and was associated with the combined effects of decreased g s and decreased leaf N concentrations in response to growth under elevated CO 2 .
Infarct artery reocclusion after primary angioplasty, stent placement, and thrombolytic therapy for acute myocardial infarction.

Abstract Background The benefits of thrombolytic therapy for acute myocardial infarction (AMI) are limited by reocclusion of the infarct-related artery, which occurs in 25% to 30% of patients after successful reperfusion. The frequency of reocclusion after balloon angioplasty and stenting in this setting is less well documented. The aim of this study was to analyze the frequency and timing of reocclusion after percutaneous transluminal coronary angioplasty (PTCA) and stent placement during AMI from all available studies compared with previously published reocclusion rates after thrombolysis. Methods and Results The previously published thrombolysis data included 4231 patients in 19 studies with ≥75 patients. Only PTCA studies with ≥50 patients and stent studies with ≥30 patients, in which routine angiographic follow-up was obtained in ≥60% of patients, were included. Ten PTCA studies with a total of 1943 patients were analyzed, with follow-up angiography in 1391 (72%). Reocclusion rates ranged from 5% to 16.7%. The stent studies included 698 patients from 7 studies, with follow-up angiography in 92%. Reocclusion rates ranged from 0% to 6%. With the use of logistic regression analysis with allowance for overdispersion, there was a significantly lower rate of reocclusion after PTCA (odds ratio, 0.38; confidence interval, 0.24 to 0.57; P P P Conclusions Reocclusion after PTCA and stent placement during AMI is less frequent than after thrombolysis. This may contribute to the superior outcome of patients treated with PTCA and stent placement in this setting. (Am Heart J 2001;141: 704-10.)
dReal: an SMT solver for nonlinear theories over the reals

We describe the open-source tool dReal, an SMT solver for nonlinear formulas over the reals. The tool can handle various nonlinear real functions such as polynomials, trigonometric functions, exponential functions, etc. dReal implements the framework of δ-complete decision procedures: It returns either unsat or δ-sat on input formulas, where δ is a numerical error bound specified by the user. dReal also produces certificates of correctness for both δ-sat (a solution) and unsat answers (a proof of unsatisfiability).
Choice’s Consequences

We will begin this chapter with a few results about countability whose proofs illustrate the difference between AC N , DC and AC, but our main task is to establish some important consequences of the full Axiom of Choice, including the basic laws of cardinal arithmetic. The telltale mark (AC) will grace practically all the numbered propositions.
Factors affecting return of symptoms 1 year after treatment in a 62-week controlled study of fluoxetine in major depression.

Background: In spite of impressive results in acute studies, the long-term treatment of major depression remains problematic. To explore the return of depressive symptoms and their interaction with social factors on long-term outcome, we assessed 55 patients whose depression had been treated during a 62-week, fluoxetine maintenance study, 1 year after the study's termination. Method: During the year following the study termination, patients were free to select treatment options. Assessments at the 1-year follow-up included measures of depressive symptoms (using the Hamilton Rating Scale for Depression [HAM-D]), social and marital impairment (using the Weissman Social Adjustment Scale [SAS]), personal stressors (using the Holmes Social Readjustment Rating Scale), and history of treatment during the past year. Results: At the time of the naturalistic follow-up, 53% of patients sustained their improvement in mood. Factors associated with return of depressive symptoms included personal stresses, marital maladjustment, personal decision to discontinue antidepressants, and medication failure. Psychosocial variables were associated with poor outcome in over 90% of impaired subjects. Development of subsyndromal symptoms during the 50-week double-blind phase was predictive of poorer outcome at the long-term follow-up. Conclusion: The study demonstrates that no matter how effective initial pharmacologic therapy may be, without ongoing clinical monitoring and support, particularly in dealing with issues such as marriage and handling significant life stresses, and compliance with medications, it will not be successful in the long-term treatment for a significant portion of patients with depression.
Educating Leadership for Effecting Community Change through Voluntary Associations

Abstract Voluntary associations are an indispensable tool for placing capacity development issues high on local communities' agendas for action—issues including primary prevention in mental health and health, employment, and social justice. This paper identifies leadership problems faced by professional social workers in their efforts to mobilize voluntary associations to pursue social change objectives at the local level. Professional and volunteer performance of six leadership functions have proven effective in dealing with these problems. The authors conclude that schools of social work should take broad initiatives to refocus attention on voluntary associations and their potential effectiveness as vehicles for social change.
Image as language: Teacher-created photographs and visual literacy for English language learning:

Language is not learned through words alone; images lie at the heart of language development. This article suggests three essential guidelines for teachers as they create and use photographs for content learning, second-language development and image-reading. Each guideline is accompanied by content, visual literacy and language objectives. Photographs and sets of sample-levelled questions exemplify the use of the language objectives for content and visual learning in social studies, geometry or science. In sum, an informed use of visual imagery can enhance the exploration of curriculum content if based on teacher knowledge of content, of the language through which photographs speak, and of the language needed to talk about both content and image.
A Conceptual Design Environment for Technology Selection and Performance Optimization for Torpedoes

Presented at the 9th Multi-Disciplinary Analysis and Optimization Symposium in Atlanta, GA, September 4-6, 2002.
Radiation Transfer in Whispering-Gallery Mode Microcavities

Micro/nanoscale radiation transfer in whispering-gallery mode (WGM) microcavities is investigated. Each cavity consists of a waveguide and a microdisk coupled in a planar chip. In order to characterize the WGM resonance phenomena, studies of configuration parameters, specifically the microdisk size, the gap distance separating the microdisk and waveguide, and the waveguide width are numerically conducted. The finite element method is used for solving Maxwell’s equations which govern the propagation of electromagnetic (EM) field and the radiation energy transport in the micro/nanoscale WGM structures. The EM fields and the radiation energy distributions in the microcavities are then obtained. The scattering spectra for three different microdisk sizes are also obtained; and through which the WGM resonant properties such as the quality factor, the full-width at half maximum (FWHM), the free spectral range, and the finesse of the resonant modes are analyzed. It is found that the resonant frequencies and their free spectral ranges are predominantly determined by the size of the microcavity; while the FWHM, finesse, and quality factor are strong functions of the gap.Copyright © 2005 by ASME
Application of weight grade method in comprehensive assessment of immunization programs of county level

Objective To discuss overall evaluation in immunization programs.Methods Weighted method was applied to comprehensively evaluate immunization programs in 2011.Results Year-end examination and quarterly selective examination data were taken to establish evaluation index system of immunization programs,and calculate comprehensive index queuing.The comprehensive evaluation result was objective,comprehensive,accurate and reliable.Conclusions The weighted method is simple to learn,scientific and practical,feasible to evaluate immunization programs.It is worth popularizing for it can evaluate immunization scientifically and objectively.
Screening and Molecular Analysis of Single Circulating Tumor Cells Using Micromagnet Array

Immunomagnetic assay has been developed to detect rare circulating tumor cells (CTCs), which shows clinical significance in cancer diagnosis and prognosis. The generation and fine-tuning of the magnetic field play essential roles in such assay toward effective single-cell-based analyses of target cells. However, the current assay has a limited range of field gradient, potentially leading to aggregation of cells and nanoparticles. Consequently, quenching of the fluorescence signal and mechanical damage to the cells may occur, which lower the system sensitivity and specificity. We develop a micromagnet-integrated microfluidic system for enhanced CTC detection. The ferromagnetic micromagnets, after being magnetized, generate localized magnetic field up to 8-fold stronger than that without the micromagnets, and strengthen the interactions between CTCs and the magnetic field. The system is demonstrated with four cancer cell lines with over 97% capture rate, as well as with clinical samples from breast, prostate, lung, and colorectal cancer patients. The system captures target CTCs from patient blood samples on a standard glass slide that can be examined using the fluorescence in-situ hybridization method for the single-cell profiling. All cells showed clear hybridization signals, indicating the efficacy of the compact system in providing retrievable cells for molecular studies.
(3H) Opiate binding: anomalous properties in kidney and liver membranes.

[3H]Naloxone and [3H]dihydromorphine bind in a saturable fashion and with high affinity to membrane preparations of guinea pig kidney and liver. Binding in guinea pig kidney displays "reversed" stereospecificity, with pharmacologically inactive dextrallorphan being more potent than the known pharmacologically active levallorphan. Opiate agonists tend to be more potent than their corresponding antagonists in competing for [3H]opiate binding in guinea pig kidney. Unlike brain opiate receptors, in which sodium and manganese selectively decrease and increase, respectively, the binding of [3H]opiate agonists, these ions have no selective effect on the binding of [3H]opiates in guinea pig kidney and liver. The opioid peptides Met-enkephalin and β-endorphin and the opiates etorphine and diprenorphine, which have very high affinity for brain opiate receptors, have negligible effects on [3H]opiate binding in guinea pig kidney.
Introduction: 50 years of evolution of contraceptive medicine.

The science of contraceptive medicine and reproductive medicine are similar. At present contraceptive medicine has moved beyond understanding the mechanism of action of steroid hormones with the introduction of many safe and effective methods. Long-acting reversible contraceptives are increasing in acceptance and providing very high efficacy. The science has pivoted toward optimization of family planning in selected high-risk populations, such as those with a high-risk of thrombosis, as well as addressing the challenge of obesity. The pipeline for male and female related methods will continue to advance the science and public health impact.
Religion-motivated Enterprises in the Marketplace: A Macromarketing Inquiry

This exploratory essay identifies and examines a variety of religiously affiliated or inspired enterprises operating in otherwise secular marketplaces. While explicitly recognizing that some market...
Synthetic small molecule epigenetic modulators as antitumor agents

H demethylases such as lysine-specific demethylase 1 (LSD1) mediate an important cellular mechanism for epigenetic control of gene expression. In particular, histone H3 dimethyl lysine 4 (H3K4me2) is a transcription activating chromatin mark at gene promoters, and aberrant demethylation of this mark by LSD1 may broadly repress the expression of tumor suppressor genes that are important in human cancer. We, and others, have conducted studies verifying that LSD1 is an exciting new therapeutic target. We reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of recombinant human LSD1. These inhibitors significantly increase H3K4me2 levels, initiate chromatin remodeling and induce the re-expression of tumor suppressor genes. The potent LSD1 inhibitor 2d promoted re-expression of multiple, aberrantly silenced genes important in the development of colon cancer, including members of the secreted frizzle-related proteins (SFRPs) and the GATA family of transcription factors. We were the first to demonstrate the antitumor effects of LSD1 inhibitors in vitro and have recently demonstrated their significant antitumor effects in vivo. Based on this lead, and on a recently conducted virtual screen, we have now identified additional LSD1 inhibitors and begun to elucidate structure/activity relationships for inhibition of LSD1. In this presentation, the syntheses leading to these analogues, their characterization as LSD1 inhibitors, their cellular effects and their evaluation as antitumor agents will be discussed. Patrick M. Woster, Med chem 2013, 3:4 http://dx.doi.org/10.4172/2161-0444.S1.009
Abstract 3117: Hsa-miR-140-5p inhibits colorectal cancer stem cell invasion and metastasis by suppressing Smad2 and autophagy

Colorectal cancer is one of the most common cancers and frequently metastasizes to the liver. TGF-β signaling has been shown to regulate cancer metastasis by promoting epithelial to mesenchymal transition and cancer stem cell (CSC) phenotypes. Smad2 is a key element downstream of TGF-β. In this study, we showed that hsa-hsa-miR-140-5p-5p directly targets Smad2 and overexpression of hsa-miR-140-5p in colorectal cancer cell lines decreases Smad2 expression level, which leads to decreased level of cell invasion and proliferation, as well as increasing cell cycle arrest. Ectopic expression of hsa-miR-140-5p in colorectal CSCs inhibited CSC growth and sphere formation in vitro by disrupting autophagy, an essential process for cancer cell survival and chemoresistance. We have systematically identified the targets of hsa-miR-140-5p involved in autophagy. Furthermore, overexpression of hsa-miR-140-5p in CSCs abolished the tumor formation as well as metastasis in vivo by using subcutaneous xenografts and tail vein injection of CSCs in NOD/SCID mice. In addition, there is a progressive loss of hsa-miR-140-5p expression from normal colorectal mucosa to primary tumor tissues, with further reduction in liver metastatic tissues, quantified by qRT-PCR. The functional and clinical significance of hsa-miR-140-5p suggests that it is a key regulator in colorectal cancer progression and metastasis. As a result, it may have potential as a novel therapeutic molecule to treat colorectal cancer. Citation Format: Haiyan Zhai, Andrew Fesler, Jingfang Ju. Hsa-miR-140-5p inhibits colorectal cancer stem cell invasion and metastasis by suppressing Smad2 and autophagy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3117. doi:10.1158/1538-7445.AM2015-3117
Statistical Issues in Forensic Science

Forensic science refers to the use of scientific methods in a legal context. Several recent events, especially the release in 2009 of the National Research Council (NRC) report Strengthening Forensic Science in the United States: A Path Forward, have raised concerns about the methods used to analyze forensic evidence and the ways in which forensic evidence is interpreted and reported on in court. The NRC report identified challenges including the lack of resources in many jurisdictions compared with the amount of evidence requiring processing, the lack of standardization across laboratories and practitioners, and questions about the analysis, interpretation and presentation of evidence. With respect to the last, the NRC report raises questions about the underlying scientific foundation for forensic examinations on some evidence types. Statistics has emerged as a key discipline for helping the forensic science community address these challenges. The standard elements of statistical analysis—study design, d...
Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury after ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood–brain barrier is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in blood–brain barrier integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.
The Use of Sildenafil for Glomerular Disease.

Transient receptor potential channel 6 (TRPC6) is a Ca2+ ion transport channel associated with the slit diaphragm of podocytes, and is indispensable for regulation of structural components of podocytes and renal function.[1][1] Since the discovery of a TRPC6 gain-of-function mutation that causes
Sensitivity Analyses over the Service Area for Mobility Allowance Shuttle Transit (MAST) Services

A Mobility Allowance Shuttle Transit (MAST) system is an innovative concept that merges the flexibility of Demand Responsive Transit (DRT) systems with the low cost operability of fixed-route bus systems. It allows vehicles to deviate from the fixed path so that customers within the service area may be picked up or dropped off at their desired locations. In this paper, we summarize the insertion heuristic presented by Quadrifoglio et al. (2007) for routing and scheduling MAST services, and we carry out a set of simulations to show a sensitivity analysis of the performance of the algorithm and the capacity of the system over different shapes of the service area. The results show that a slim service area performs better in general, but also that the positive effects of a proper setting of the control parameters of the heuristic is much more evident for wider service areas. In addition, a performance comparison shows that MAST systems can provide a better service to customers than fixed-route ones even for a slim service area.
Unusual Electronic Structure of the Donor–Acceptor Cocrystal Formed by Dithieno[3,2-a:2′,3′-c]phenazine and 7,7,8,8-Tetracyanoquinodimethane

Mixed cocrystals derived from electron-rich donor (D) and electron-deficient acceptor (A) molecules showcase electronic, optical, and magnetic properties of interest for a wide range of applications. We explore the structural and electronic properties of a cocrystal synthesized from dithieno[3,2-a:2′,3′-c]phenazine (DTPhz) and 7,7,8,8-tetracyanoquinodimethane (TCNQ), which has a mixed-stack packing arrangement of the (π-electronic) face-to-face stacks in a 2:1 D:A stoichiometry. Density functional theory investigations reveal that the primary electronic characteristics of the cocrystal are not determined by electronic interactions along the face-to-face stacks, but rather they are characterized by stronger electronic interactions orthogonal to these stacks that follow the edge-to-edge donor–donor or acceptor–acceptor contacts. These distinctive electronic characteristics portend semiconducting properties that are unusual for semiconducting mixed cocrystals and suggest further potential to design organic s...
Spatiotemporal variability in building energy use in New York City

Abstract Data on building energy use for large and dense cities is not yet available at adequate spatial and temporal scales. The energy consumption from buildings significantly influences the local climate and this impact is not adequately integrated into regional or local scale weather models. The primary objective of his study is to understand and map building energy consumption and quantify its impact on the urban environment; here, New York City (NYC) is used as a test case. The project involved a detailed classification of buildings in NYC using a high-resolution landuse/landcover dataset. The customized classification was then coupled with a single building energy model (SBEM) to estimate the building energy use. The developed model matched the annual energy use of NYC within 5% of the observed value. Coupled energy simulations were then performed with the Weather Research and Forecasting (WRF) model. The results show that heat released from building's heating and air conditioning system during extreme heat events can be as high as 18% of the overall available energy. Finally, a comparison between the average annual energy use, the urban heat island intensity (UHI) and the landcover/landuse fraction for various parcels during extreme heat events indicated that neighborhoods surrounding the highly-commercialized zones were disproportionately impacted by high UHI values. The increase was related to advection of heat.
Medicare and the Affordable Care Act: Fraud Control Efforts and Results

Medicare fraud and abuse costs are estimated at 3–10% of overall Medicare spending, which is expected to expand considerably until 2024 and as such the amount of fraud dollars would be expected to ...
American Democracy and Its Spaces: An Introduction

The introduction explains that the book—using the landscape and urban design visions of Jefferson, Thoreau, Olmsted, Wright, Moses, and several new urbanists—provides a unique history of American democratic ideas. Moreover, to set the stage for the rest of the project, the chapter describes different models of democracy, seeks to define and differentiate landscape and urban design, and offers a brief account of why spatial philosophy matters for politics. Finally, it spells out the book’s key normative claim, to wit, that a communally oriented democratic theory and its associated urban designs strike a better balance than individualistic theories and their built spaces—that the former are able to combine the protection of individual liberty with the nurturing of civic practices and values.
Birds and Burrows: Avifauna Use and Visitation of Burrows of Gopher Tortoises At Two Military Sites In the Florida Panhandle

ABSTRACT.— The United States Department of Defense (DoD) has a dual mission of maintaining military readiness and stewardship of its natural resources. The DoD invests more than $334 million on land and species management on their properties, which support high levels of biodiversity and harbor a disproportionate number of threatened, endangered, and at-risk species. The gopher tortoise (Gopherus polyphemus) occurs on 28 DoD installations in the southeastern United States. Because more than 350 species have been documented to use their burrows, the gopher tortoise is considered a keystone species. However, few species of birds have previously been documented as burrow associates. In this study, we compare bird species richness, visitation frequency, and behaviors at gopher tortoise burrows at two Department of Navy properties (Santa Rosa County, Florida) that differed in size, training intensity, habitat diversity, and proportion of habitat suitable for gopher tortoises. We detected a total of 33 species ...
Distal clavicle fracture radiography and treatment: a pictorial essay

Fractures of the distal clavicle represent 15-30% of all clavicle fractures. The local osseoligamentous anatomy and deforming forces result in increased risk of delayed union and nonunion than fractures in other parts of the clavicle. These factors also contribute to challenges in fracture repair. Understanding these injuries and their imaging features enhances care and ensures patients are directed to appropriate management. We review the anatomy of the distal clavicle and surrounding ligaments, options for radiographic evaluation, relevant classification systems, and current concepts in management. Illustrative examples of specialized views are provided. Pediatric acromioclavicular joint pseudosubluxation is also reviewed, with findings specific to that injury.
Energy-Efficient Deep In-memory Architecture for NAND Flash Memories

This paper proposes an energy-efficient deep in-memory architecture for NAND flash (DIMA-F) to perform machine learning and inference algorithms on NAND flash memory. Algorithms for data analytics, inference, and decision-making require processing of large data volumes and are hence limited by data access costs. DIMA-F achieves energy savings and throughput improvement for such algorithms by reading and processing data in the analog domain at the periphery of NAND flash memory. This paper also provides behavioral models of DIMA-F that can be used for analysis and large scale system simulations in presence of circuit non-idealities and variations. DIMA-F is studied in the context of linear support vector machines and k-nearest neighbor for face detection and recognition, respectively. An estimated 8×-to-23× reduction in energy and 9×-to-15× improvement in throughput resulting in EDP gains up to 345× over the conventional NAND flash architecture incorporating an external digital ASIC for computation.
Virtual Safe: Unauthorized Walking Behavior Detection for Mobile Devices

The prevalence and monetary value of mobile devices, coupled with their compact and, indeed, mobile nature, lead to frequent theft due to a lack of proper anti-theft mechanisms. Currently, there only exist damage control efforts such as remote wiping the device's memory or GPS tracking, but nothing to notify users of theft while it takes place. We propose such a mechanism which utilizes the unique walking patterns inherent to humans and differentiate our work from other walking behavior studies by using it as first-order authentication and developing matching methods fast enough to act as an actual anti-theft system. We test our system with the aid of 45 volunteers and demonstrate detection of unauthorized movement within 10 to 20 steps with an accuracy of 96.4 to 98.4 percent, while simultaneously distinguishing owners as themselves with 97.8 percent accuracy.
Mycobacterium abscessus Infections in Children: A Review of Current Literature

There is limited literature on Mycobacterium abscessus infections in children and limited data about its diagnosis and management. The incidence of infections due to M abscessus appears to be increasing in certain populations and can be a significant cause of morbidity and mortality.Management of these infections is challenging and relies on combination antimicrobial therapy and debridement of diseased tissue, depending on the site and extent of disease. Treatment regimens often are difficult to tolerate, and the antimicrobials used can cause significant adverse effects, particularly given the long duration of therapy needed.This review summarizes the literature and includes information from our own institution's experience on pediatric M abscessus infections including the epidemiology, transmission, clinical manifestations, and the management of these infections. Adult data have been used where there are limited pediatric data. Further studies regarding epidemiology and risk factors, clinical presentation, optimal treatment, and outcomes in children are necessary.
Sorting Large Datasets with Heterogeneous CPU/GPU Architectures

We examine heterogeneous sorting for input data that exceeds GPU global memory capacity. Applications that require significant communication between the host and GPU often need to obviate communication overheads to achieve performance gains over parallel CPU-only algorithms. We advance several optimizations to reduce the host-GPU communication bottleneck, and find that host-side bottlenecks also need to be mitigated to fully exploit heterogeneous architectures. We demonstrate this by comparing our work to end-to-end response time calculations from the literature. Our approaches mitigate several heterogeneous sorting bottlenecks, as demonstrated on single- and dual-GPU platforms. We achieve speedups up to 3.47x over the parallel reference implementation on the CPU. The current path to exascale requires heterogeneous architectures. As such, our work encourages future research in this direction for heterogeneous sorting in the multi-GPU NVLink era.