cssi/SciSciGPT-SciSciNet huggingface dataset:
Oral vitamin E supplementation on oxidative stress, vitamin and antioxidant status in intensely exercised horses

Summary Reasons for performing study: Vitamin E is the most commonly supplemented antioxidant in horses; however, previous research is not conclusive as to the recommended level for exercising horses. Objective: To evaluate the effects of 3 levels of vitamin E supplementation on oxidative stress and vitamin/antioxidant status in intensely exercised horses to determine the optimal level of vitamin E supplementation. Methods: Twelve unfit Standardbreds were divided into 3 groups, supplemented orally with 0 (CON), 5000 (MOD), or 10,000 (HI) iu/day of DL-α-tocopheryl acetate. The 3 times 3 Latin square design consisted of three 4 week supplementation periods with 4 week wash out periods between. After each period, horses underwent a treadmill interval exercise test. Blood samples were collected and heart rate (HR) measured before, during and after exercise. Data were analysed using ANOVA with repeated measures in SAS. Results: The CON group had lower HR throughout the test compared to the MOD and HI groups (P<0.05). There was an increase in plasma retinol (RET), β-carotene (BC), red blood cell total glutathione and glutathione peroxidase with exercise (P<0.05), but all groups returned to baseline after 24 h. Plasma α-tocopherol (TOC) increased from baseline with exercise (P<0.0001) in all groups; treatment differences were observed at 24 h (P<0.05). The HI and CON groups had lower BC compared to the MOD group (P = 0.05). Conclusions: Horses supplemented with vitamin E, at nearly 10-times the 1989 NRC recommended level, did not experience lower oxidative stress compared to control horses. Additionally, lower plasma BC levels observed in the HI group, which may indicate that vitamin E has an inhibitory effect on BC metabolism. Potential relevance: Supplementation above control levels is not more beneficial to oxidative stress and antioxidant status in intensely exercising horses; indeed, levels 10 times in excess may be detrimental to BC and should be avoided.
E-Textile Conductors and Polymer Composites for Conformal Lightweight Antennas

We present a conformal and lightweight antenna technology based on E-textile conductors and polymer-ceramic composites. Unique advantages of the proposed technology are its structural integrity, light weight and conformity to the platform. E-textile conductors are fabricated with single wall carbon nanotube (SWNT) and Ag coated textiles. They demonstrate good structural integrity with polymer composites due to their mechanical compatibility. Similarly, polymer composites demonstrate superior RF performance with permittivity ranging from 3 to 13. Fabrication process for E-textile conductors and integration process with polymer composites is described in detail. We also demonstrated merit of the proposed technology with a simple patch antenna whose radiation performance is measured when it was flat and conformed onto a cylindrical surface. We compared its performance with that of an ideal patch. Experiments suggested that the sample patch antenna based on the proposed technique achieved 6 dB gain, which is 2 dB below a patch which has the same dimensions and made of ideal lossless materials. When it is conformed onto a cylindrical surface, we achieved 2.5 dB less gain than that of antenna realized with a PEC surface. This clearly validates the merit of the proposed conformal antenna technique based on non-traditional materials.
Performance estimation and slack matching for pipelined asynchronous architectures with choice

This paper presents a fast analytical method for estimating the throughput of pipelined asynchronous systems, and then applies that method to develop a fast solution to the problem of pipelining "slack matching." The approach targets systems with hierarchical topologies, which typically result when high-level (block structured) language specifications are compiled into data-driven circuit implementations. A significant contribution is that our approach is the first to efficiently handle architectures with choice (i.e., the presence of conditional computation constructs such if-then-else and conditional loops).The key idea behind the fast speed of our analysis method is to exploit information about the hierarchy of a given block-structured system, thereby yielding a runtime that is linear in the number of pipeline stages. In contrast, existing approaches typically represent an entire system as a single Petri net or marked graph, and then apply Markov chain analysis or other state enumeration methods with costly runtimes.Building upon our analysis approach, we introduce a novel solution to the problem of slack matching, i.e., determining optimal insertion of FIFO stages into a pipelined design to improve performance. We present both an optimal solution using an MILP formulation, and a fast heuristic algorithm that yielded optimal results for all of our examples.
Factors controlling aminoacyl-transfer-ribonucleic acid synthesis in vitro by a plant system.

Abstract 1. Factors affecting aminoacyl-tRNA synthesis in vitro by cell-free preparations from bean leaves were investigated. 2. Evidence was obtained that optimum concentrations as well as correct ratios of Mg2+ and ATP are required for aminoacyl-tRNA synthesis in the bean-leaf system. 3. The results indicated that pH is a controlling factor having differential effects on the formation of individual aminoacyl-tRNA species. The possible micro-regulatory function of pH in protein synthesis in vivo is discussed with special reference to alanyl-tRNA formation. 4. Very low rates of alanine-stimulated pyrophosphate exchange were observed in the absence of tRNA. This observation is discussed relative to proposals about the mechanism of aminoacyl-tRNA synthesis.
John Macmurray's personal universe

John Macmurray, philosophe ecossais (1891-1971) articule la methode philosophique a la foi chretienne pour sa recherche de la verite. Pour lui, la religion represente la forme primitive et ultime de la rationnalite reflexive et pratique. La religion ne designe pas seulement la forme veritable du savoir personnel mais aussi la forme de l'action. Dans cette perspective philosophique, la religion n'est pas d'abord une suite de traditions, de rites, de doctrines ou de voies specifiques de vie spirituelles mais un champ entier d'experience commune en rapport avec la relation personnelle d'ou l'importance de la communaute chez Macmurray.
Static Dipole Polarizabilities of C, N, O and F: The Importance of Spin Projection

The static dipole polarizability for the ground state of C(3Π), N(4Σ+), O(3Π) and F(2Σ+) have been calculated using ab initio molecular orbital techniques. The polarizabilities are obtained from unrestricted Hartree-Fock and Many-Body Perturbation Theory wave functions with and without spin projection, which are computed by finite-field differentiation. The effect of spin contamination is shown to be important on the calculation of static dipole polarizabilities for the ground state of C, N, O and F.
Aggressive secondary surgery for local recurrence of pancreatic cancer

We report two cases of locally recurrent pancreatic cancer treated with repeated resection. In both cases, local recurrence was found in the cut end of the remnant pancreas after initial pancreatic resection, and total remnant pancreatectomy was performed. The postoperative course was uneventful and long-term survival was achieved. Aggressive repeated surgical resection could improve the prognosis of selected patients who are suffering from local recurrence of pancreatic cancer, and can be considered as a treatment option.
Mountain Pine Beetle (Coleoptera: Scolytidae) Mortality in Three Types of Infestations

Populations of mountain pine beetles, Dendroctonus ponderosae Hopkins (Coleoptera: Scolytidae), in lodgepole pine, Pinus contorta var. latifolia Engelmann, were sampled at three heights within trees in endemic, epidemic, and postepidemic infestations. Eight mortality factors were evaluated: competition within and between broods, parasites, predators, pathogens, winter temperature, drying of the phloem, pitch, and unexplained mortality. Beetle survival was significantly greater ( P 0.05) by height in trees. Parasites and predators accounted for 8, 33, and 4% of total mountain pine beetle losses in endemic, epidemic, and postepidemic infestations, respectively. Medetera (13%) and woodpeckers (15%) accounted for the greatest amount of predation, and this occurred during epidemic infestations. Most parasites and predators showed the typical density-dependent response. Clerids were the single exception, taking a greater proportion of beetles in endemic infestations, thus suggesting a role by clerids in keeping mountain pine beetle populations at an endemic level. However, clerids accounted for only 0.9% of beetle losses.
The relationship between apoptosis and expression of P27 protein in hepatocellular carcinoma

Objective To study The relationship between apoptosis and expression of P27 protein in hepatocellular carcinoma(HCC).Methods P27 protein and apoptotic cells were detected by immunohistochemical S-P method and TUNEL method in 86 paraffin-embedded tissues of HCC.Results The positive rate of P27 protein in these tissues was 37.2%(32/86). The mean apoptotic index in the HCC with positive expression of P27 protein (6.72‰) was significantly higher than that in the negative group (2.83‰). Conclusion Expression of P27 protein related significantly with cell apotosis of HCC. Promoting apoptosis may be one of the effective anti-cancer mechanisms of P27 protein.
Quasimonotone schemes for scalar conservation laws. Part II

In this work, the quasimonotone schemes for scalar conservation laws are introduced. These new schemes share with monotone schemes both maximum principles and convergence to the entropy solution. However, they are not necessarily first-order accurate. They include both finite-difference schemes (that are total variation diminishing (TVD)) and finite-element ones (that are not TVD), they can be either explicit or implicit; and they can be used with time-dependent grids. They can be defined for d-space variables in the case of a grid that is a Cartesian product of one-dimensional partitions. Error estimates are provided. Part I covers the quasimonotone finite-difference schemes in one dimension. Part II is devoted to quasimonotone finite-element schemes, also in one dimension. Finally, Part III discusses the general case.
Development of Vaccine-Based Immunotherapy for Murine Large B-Cell Lymphoma

Diffuse Large B Cell Lymphoma (DLBCL) is an aggressive form of Non-Hodgkin’s Lymphoma (NHL) accounting for 40% of NHL in the United States. Current treatment options are ineffective in eliminating refractory lymphoma, which is responsible for patient relapse. Therefore, a carefully developed immunotherapeutic strategy to specifically target refractory lymphoma might be useful in improving therapy. In this study, anti-lymphoma immune outcome was evaluated in a syngeneic murine model using the aggressive and highly liver metastatic RAW117-H10 lymphoma cell line that expresses the murine leukemia virus protein gp70. Anti-lymphoma immunity was generated by immunizing Balb/c mice with two peptide-based vaccines in which a T cell epitope from gp70 ( SSWDFITV) was covalently attached to the N-termini of two response-selective molecular adjuvants derived from complement component C5a: YSFKPMPLaR (EP54) and YSFKDMP(MeL)aR (EP67). In both vaccines, a protease-sensitive, double-Arg linker sequence (RR) was placed between the epitope and the EP54/EP67 molecular adjuvants: SSWDFITV- RR-YSFKPMPLaR (Vaccine 2) and SSWDFITV- RR-YSFKDMP(MeL)aR (Vaccine 3). To determine the protective effect of the EP54/EP67-containing vaccines against lymphoma growth, separate groups of Balb/c mice were administered 200 μg of Vaccine 2 or Vaccine 3 dissolved in water via intraperitoneal (100 μg) and intradermal (100 μg) injections. Following 4 weekly immunizations, the mice were intravenously transplanted with 5 × 10 3 RAW117-H10 cells to ascertain the protective benefit of the vaccines. The results showed Vaccines 2 and 3 providing complete protective benefit, with pre-vaccinated mice surviving greater than 235 days, whereas all control, unvaccinated animals died within 18 days of tumor inoculation. In addition to survival analysis, histopathological analysis was performed using liver sections from mice upon death, or after sacrifice following 60 days of survival, to evaluate tumor burden in the mice (See Figure 1). No tumor growth was found in livers taken from mice pre-vaccinated with Vaccines 2 and 3. Furthermore, to elucidate the mechanisms of vaccine-mediated protection against lymphoma, the frequency and functions of the immune effector cells from blood and spleens were analyzed at 72 hours following the second and fourth vaccinations using flow cytometry, T and B cell-specific mitogen proliferation assays, and lymphoma-specific cytotoxicity assays in vitro . The results of these analyses showed a significant increase in the frequency (p
Muscle Activation During Pilates Exercises in Participants With Chronic Nonspecific Low Back Pain: A Cross-Sectional Case-Control Study

Abstract Objective To determine the amplitude of the electromyographic activity of trunk muscles during Pilates exercises in women with and without chronic low back pain (LBP). Design Case-control study. Setting University physical therapy clinic. Participants Women (N=60) divided into an LBP group and a control group. Interventions Not applicable. Main Outcome Measures Amplitude of the electromyographic activity (root mean square values) of the gluteus maximus and external oblique muscles collected during 3 Pilates exercises: Shoulder Bridge performed on the mat, and Hip Roll and Breathing performed in equipment. Pain intensity was assessed in the LBP group. Results The amplitude of the electromyographic activity was similar between groups ( P ≥.05). For both groups, the amplitude of the gluteus maximus was higher in the Shoulder Bridge exercise compared with the Hip Roll with 2 springs (control group: mean difference [MD]=.18; 95% confidence interval [CI], .05–.41; LBP group: MD=.29; 95% CI, .16–.31) and the Breathing exercise (control group: MD=−.40; 95% CI, −.55 to −.26; LBP group: MD=−.36; 95% CI, −.52 to −.20). The amplitude of the external oblique muscle was higher in the Shoulder Bridge compared with the Hip Roll with 2 springs (control group: MD=.13; 95% CI, .05–.21; LBP group: MD=.18; 95% CI, .03–.33). Pain intensity increased after exercises, but this increase was lower for the mat exercises. Conclusions Similar muscle activation between groups was found. The findings suggest that mat exercises caused less pain and a greater difference in the amplitude of muscle activation compared with the equipment-based exercises.
Finding Synergy Among Research, Teaching, and Service: An Example from Mathematics Education Research

Being a faculty member in higher education involves the balance and integration of various roles and demands. In this chapter I present my own story, as a mathematics education researcher in the teaching and learning of undergraduate mathematics focusing on linear algebra. Using my experience as an example, I describe how synergy among research, teaching, and service can impact career goals and institutional needs.
Abstract 2948: Combination treatment of PARP inhibitor, BMN 673 and DNMT inhibitor, Azacytidine: A potential therapy for BRCA negative and positive, triple negative breast cancers

Poly-ADP-ribose polymerase inhibitors (PARPis) represent one of the most exciting recent developments in cancer therapy and have shown efficacy in a minority (5-10%) of triple negative (estrogen, progesterone and herceptin receptor negative) breast cancers (TNBCs) with inherited mutations in breast cancer genes BRCA1/2 (BRCA-ve). In PARPi clinical trials, approximately of 60% BRCA-ve patients showed responses, while a significant proportion did not. In addition, sporadic TNBCs with intact BRCA1/2 have failed PARPi therapy. This suggests the urgent need for additional novel therapies for breast cancer. Our studies are underpinned by 4 important findings: (1) the development of a new class of potent PARPis exemplified by BMN 673, (2) the mechanism of cytotoxicity of PARPis, including BMN 673, is attributed to its ability to trap PARP-DNA complexes in chromatin, (3) unpublished findings by our group that PARP interacts with epigenetic factors such as DNMT1 in a high molecular weight complex on chromatin in response to DNA damage and (4) DNMT inhibitors (DNMTis) such as FDA approved Azacytidine (AzaC) covalently trap DNMTs in DNA as their mechanism of action. Therefore, the interaction of PARP and DNMT1 suggest a therapeutic opportunity for combining PARPis and DNMTis in an effort to enhance the effects of PARPi therapy. We first set out to determine whether a combination of these two drugs would enhance trapping of PARP-DNA complexes in chromatin, leading to increased cytotoxicity of TNBC. We treated MDA-MB-231 with BMN 673 (10-100nM) or AzaC (150nM) alone, or the two drugs in combination, and measured PARP trapping in chromatin extracts following induction of DNA damage by radiation (2Gy) after 72hrs. As expected, BMN 673 treatment leads to PARP trapping as determined by western blotting of proteins from chromatin extracts. Interestingly, treatment with AzaC treatment alone also leads to the presence of PARP in chromatin. Importantly, AzaC in combination with BMN 673 treatment shows an at least a 2-fold increase in PARP trapping, compared to the individual drug treatments. To determine whether PARP trapping correlates with cytotoxicity and cell death, BRCA+ve TNBC lines MDA-MB-231 and MDA-MB-468 and BRCA-ve TNBC lines SUM149PT and HCC1937 cells were treated with the drugs alone and in combination and placed in colony forming assays. Compared with single drug treatments, the combination treatment showed a significant (p Citation Format: Khadiza Chowdhury, Rena G. Lapidus, Eun Yong Choi, Stephen Baylin, Feyruz V. Rassool. Combination treatment of PARP inhibitor, BMN 673 and DNMT inhibitor, Azacytidine: A potential therapy for BRCA negative and positive, triple negative breast cancers. [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 2948. doi:10.1158/1538-7445.AM2015-2948
Ensemble learning for effective run-time hardware-based malware detection: a comprehensive analysis and classification

Malware detection at the hardware level has emerged recently as a promising solution to improve the security of computing systems. Hardware-based malware detectors take advantage of Machine Learning (ML) classifiers to detect pattern of malicious applications at run-time. These ML classifiers are trained using low-level features such as processor Hardware Performance Counters (HPCs) data which are captured at run-time to appropriately represent the application behaviour. Recent studies show the potential of standard ML-based classifiers for detecting malware using analysis of large number of microarchitectural events, more than the very limited number of HPC registers available in today’s microprocessors which varies from 2 to 8. This results in executing the application more than once to collect the required data, which in turn makes the solution less practical for effective run-time malware detection. Our results show a clear trade-off between the performance of standard ML classifiers and the number and diversity of HPCs available in modern microprocessors. This paper proposes a machine learning-based solution to break this trade-off to realize effective run-time detection of malware. We propose ensemble learning techniques to improve the performance of the hardware-based malware detectors despite using a very small number of microarchitectural events that are captured at run-time by existing HPCs, eliminating the need to run an application several times. For this purpose, eight robust machine learning models and two well-known ensemble learning classifiers applied on all studied ML models (sixteen in total) are implemented for malware detection and precisely compared and characterized in terms of detection accuracy, robustness, performance (accuracy × robustness), and hardware overheads. The experimental results show that the proposed ensemble learning-based malware detection with just 2 HPCs using ensemble technique outperforms standard classifiers with 8 HPCs by up to 17%. In addition, it can match the robustness and performance of standard ML-based detectors with 16 HPCs while using only 4 HPCs allowing effective run-time detection of malware.
Multidimensional Finite Volume Fully Implicit Ablation and Thermal Response Code

A finite volume, fully implicit ablation and thermal response code that simulates the pyrolysis gas flow, thermochemical ablation, and shape change of thermal protection materials and systems in mu...
Oral, dental, and supportive care in the cancer patient.

Patients undergoing chemotherapy and/or head and neck radiation treatment may have multiple side effects occurring simultaneously such as mucositis, candidiasis, herpetic stomatitis or xerostomia. It is important to make the diagnosis(es) and treat the patient as effectively as possible on the basis of the diagnosis(es). Therapeutic management is generated by the diagnosis (Table 2). The oral and dental care management should be individualized on a case by case basis as there are so many variables involved with the cancer patient.
Attention Deficit Hyperactivity Disorder and Learning Disabilities

Attention deficit hyperactivity disorder (ADHD) and learning disabilities (LD) are the most commonly used diagnoses for children who experience academic and behavioral difficulties. Not only do questions concerning ADHD and LD comprise the majority of referrals made to psychologists, psychiatrists, and other professionals, but many children diagnosed with one of these disorders also meet diagnostic criteria for the other disorder (1). Educators, other professionals, and parents often ask questions such as: What are the differences between ADHD and LD? Why do ADHD and LD co-occur so frequently? What impact do the similarities and differences between these disorders have on developing and implementing effective interventions for these children? Although many of the current answers and debates regarding these questions can be examined within many of the chapters contained in this book, this chapter focuses on a unique aspect of ADHD—i.e., the co-occurrence of ADHD and LD. This chapter provides an overview of the definitional issues presented by ADHD and LD, and discusses the notion of comorbidity and co-occurrence of these two disorders. A major portion of this chapter is devoted to reviewing many of the key studies in which the overlap between ADHD and LD has been examined, with a particular focus on ADHD and reading disabilities (RD), ADHD and writing disabilities (WD), and ADHD and math disabilities (MD). The chapter concludes with evidence-based directions for the field based on the available literature.
Fire Fragility Functions for Steel Frame Buildings: Sensitivity Analysis and Reliability Framework

Fire fragility functions are a powerful method to characterize the probabilistic vulnerability of buildings to fire in the context of urban resilience assessment. But this method is recent and the influence of the different uncertain parameters on the functions has not been systematically studied. The first objective of this paper is to identify the prevailing parameters in constructing fire fragility functions for steel frame buildings. To this end, sensitivity analyses are conducted using Monte Carlo Simulations and a variance-based method, focusing on column failure fragilities. Fragilities for buildings with 3 to 12 stories, 0 to 3 h fire resistance rating and various occupancies are compared, assuming compartment areas ranging from 15 m2 to 80 m2. Results show that uncertainties in fire, heat transfer and structural models all generate significant variability in the fire fragility. In addition to fire load as the intensity measure, significant probabilistic parameters are the compartment geometry and openings, the thickness and thermal conductivity of fire protection, and the temperature dependent mechanical properties of steel. The second objective is to clarify the incorporation of fragility functions in a comprehensive structural fire reliability framework. A methodology for combining the functions with the ignition likelihood per year and with the fire loading in MJ/m2 is described, yielding annual probability estimates of column failure due to fire in the buildings. For a sprinklered office building designed according to prescriptive provisions, this annual probability ranges from 1.90 × 10−7 to 0.12 × 10−7 per year as a function of the building height. The probabilistic modeling techniques proposed in this paper can be used to establish consistent reliability levels in different buildings and to evaluate resilience for fire scenarios.
Improvement in Primary Care Provider Self-Efficacy and Use of Patient-Centered Counseling To Address Child Overweight and Obesity after Practice-Based Changes: Texas Childhood Obesity Research Demonstration Study.

Abstract Background: The Texas Childhood Obesity Research Demonstration project, a multicenter, multisystem approach to childhood overweight and obesity (OW/OB), included training and materials to ...
Valuing studies in higher education: Symbolic means and strategies of students negotiating their position in the library and information science field:

The library and information science field attempts to legitimize its position in higher education, in a ‘culture of uncertainty’, where boundaries are fluid. The position of LIS in the hierarchical...
Touch imprint (TI) cytology of needle core biopsies (NCB) in pathology laboratories: A practice survey of participants in the College of American Pathologists (CAP) Non Gynecologic Cytopathology (NGC) Education Program

Background Intra-procedural assessment of touch imprint (TI) cytology from needle core biopsies (NCB) is used to ensure sample adequacy and to provide immediate diagnosis in various settings. We aimed to survey laboratories for current practices on the use of cytology with NCB. Methods A voluntary supplemental questionnaire including questions on demographics, personnel involved, sites, accessioning, and reporting was sent with the College of American Pathologists (CAP) 2015 Non gynecologic Cytopathology Education Program to survey practices of cytologic assessment of NCB. Results Among 844 respondents, 403 (48%) performed cytologic assessment of NCB. Common body sites included lung (94%; 368/392), liver (87%; 340/ 392), and lymph nodes/spleen (77%; 303/392). Most of the time, a pathologist was present on-site 75% (295/393) for adequacy assessment which was usually verbally reported to the provider performing the procedure. Specimens were prepared by cytotechnologists (50%; 193 of 388) or pathologists (45%; 176 of 388) by touching the core to the slide (50%; 196 of 390) and rolling the core on the slide (45%; 177/390). Among the respondents, 19% said that cytotechnologists independently performed immediate assessment of TI of NCB. Most laboratories (69%; 264/384) evaluated air-dried slides with a modified Giemsa stain and rendered one TI/NCB combined report (87%, 334/385). Conclusions This is the first survey performed specifically to determine the practice of adequacy assessment of TI of NCB. Cytotechnologists are generally not performing adequacy assessment of TI without pathologist oversight. A single report is usually issued which includes the adequacy assessment as a part of the final report.
Drying of moist food snacks with innovative slot jet reattachment nozzle

This study was financially supported by the Center for Advanced Research in Drying (CARD), a US National Science Foundation Industry University Cooperative Research Center. CARD is located at Worcester Polytechnic Institute and the University of Illinois at Urbana-Champaign (co-site).
A novel non-peptide and orally active proteasome inhibitor overcomes bortezomib-resistance in multiple myeloma (MM) cells

6153 Bortezomib/PS-341 is a novel proteasome inhibitor for the treatment of relapsed/refractory multiple myeloma (MM) patients; however, some patients have intrinsic and others acquire resistance. Here we demonstrate that a novel non-peptide proteasome inhibitor NPI-0052 triggers apoptosis even in bortezomib-resistant patient MM cells, without altering the viability of normal cells. NPI-0052 overcomes MM cell-resistance to conventional therapies including melphalan (LR5), doxorubicin (Dox-40), and dexamethasone (MM.1R, U266, RPMI-8226) Moreover, NPI-0052 retains its anti-tumor activity in cancer cells overexpressing P-glycoprotein and altered topoisomerase-II activity. Importantly, NPI-0052 blocks MM cell growth triggered by adhesion to bone marrow stromal cells (BMSCs) and related cytokine secretion. Moreover, NPI-0052 induces MM cells apoptosis even in the presence of interleukin-6 or insulin-like growth factor-1, two major survival/anti-apoptotic factors for MM cells. NPI-0052 also overcomes the cytoprotective effects of anti-apoptotic proteins Bcl2 and Hsp27 in MM cells. NPI-0052-triggered MM cell death is associated with these events: loss of mitochondrial membrane potential; superoxide generation; release of mitochondrial proteins cytochrome-c/Smac; and activation of caspase-8/9/3. Conversely, the pan caspase inhibitor Z-VAD-fmk abrogates NPI-0052-induced apoptosis. Initial in vivo studies in animal models using either oral or intravenous administration have established the maximum tolerated dose (MTD) based on the whole blood proteasome activity. NPI-0052 decreased proteasome activity in packed whole blood lysates in a dose dependent fashion, and these data also suggest that NPI-0052 is orally active. Finally, combining NPI-0052 and bortezomib triggers synergistic apoptosis (Combination Index
Somatic Symptoms in Pediatric Patients With Chronic Pain: Proposed Clinical Reference Points for the Children's Somatic Symptoms Inventory (Formerly the Children's Somatization Inventory).

Abstracts Among youth with chronic pain, elevated somatic symptoms across multiple body systems have been associated with greater emotional distress and functional disability and could represent poor adaptation to pain. The Children's Somatic Symptoms Inventory (formerly the Children's Somatization Inventory) is commonly used to assess somatic symptoms in children. However, no studies have evaluated the clinical usefulness of the measure in the assessment of pediatric patients with chronic pain. This study evaluated the factor structure and clinical relevance of the 24-item Children's Somatic Symptoms Inventory (CSSI-24) in youth (n = 1,150) with mixed chronic pain complaints presenting to a tertiary pain clinic. The CSSI-24 total scores were equal or superior to factor scores as indicators of patients’ clinical characteristics (functional disability, pain catastrophizing, fear of pain, and anxiety and depressive symptoms) and parental catastrophizing and protective responses. Tertile-derived clinical reference points for the CSSI-24 total score ( Perspective: Clinical reference points based on the CSSI-24 total scores meaningfully differentiated youth with chronic pain on measures of emotional distress, functioning, parent catastrophizing and protective responses, and health care use. Assessing somatic symptoms could provide useful information regarding a pediatric patient's psychosocial risk, tendency to access health services, and need for enhanced care coordination.
Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis

Distinguishing malignant cells from non-neoplastic ones is a major challenge in triple-negative breast cancer (TNBC) treatment. Here, we developed a complementary targeting strategy that uses precisely matched, multivalent ligand-receptor interactions to recognize and target TNBC tumors at the primary site and metastatic lesions. We screened a panel of cancer cell surface markers and identified intercellular adhesion molecule–1 (ICAM1) and epithelial growth factor receptor (EGFR) as optimal candidates for TNBC complementary targeting. We engineered a dual complementary liposome (DCL) that precisely complements the molecular ratio and organization of ICAM1 and EGFR specific to TNBC cell surfaces. Our in vitro mechanistic studies demonstrated that DCLs, compared to single-targeting liposomes, exhibited increased binding, enhanced internalization, and decreased receptor signaling. DCLs consistently exhibited substantially increased tumor targeting activity and antitumor efficacy in orthotopic and lung metastasis models, indicating that DCLs are a platform technology for the design of personalized nanomedicines for TNBC.
Abstract 19847: Combination of QRS Duration and JT interval is More Prognostic Than the QT interval for Cardiovascular Death in an Ambulatory Population

Background: Few studies have compared the prognostic value of the QT interval and the JT interval for cardiovascular death in an ambulatory population. Hypothesis: We tested the null hypothesis that the prognostic value of the QT interval and the JT interval were the same for cardiovascular death in this ambulatory population. Methods: Resting 12-lead ECGs from 20903 ambulatory subjects at the VA Health System were recorded. Rate corrected QT and JT intervals were grouped by percentiles (75th, 90th, 95th, & 99th); the use of population percentiles allows for generalizability. The primary outcome (CV death) was obtained from state and federal databases. Multivariate Cox Regressions were used to study the associations between the QT interval, JT interval, and cardiovascular death. Results: The majority of subjects (n=18941 (91%)) were men (44 ± 8 years of age) and 9% were women 40 ± 10 years of age). Median follow-up time was 17.5 years. CVD occurred in 4% of subjects (n=884). Univariate analysis shows significant association between CVD and both QTc interval (1.6 p p 120ms), the cumulative hazards ratio was highest when combining long QRS duration with a JTc interval above the >99 th percentile ( HR= 6.9 [ 95%CI: 4.8-9.6] p HR= 5.7 [ 95%CI: 4.0-8.1] p Adjusted HR by JTc interval percentile group. Conclusion: We find the JTc interval to be a stronger prognostic indicator over the QTc interval for cardiovascular death in this ambulatory population.
Parallelism Analysis of Prominent Desktop Applications: An 18- Year Perspective

Improvements in clock speed and exploitation of Instruction-Level Parallelism (ILP) hit a roadblock during mid-2000s. This, coupled with the demise of Dennard scaling, led to the rise of multi-core machines. Today, multi-core processors are ubiquitous and architects have moved to specialization to work around the walls hit by single-core performance and chip Thermal Design Power (TDP). The pressure of innovation in the aftermath of Dennard scaling is shifting to software developers, who are required to write programs that make the most effective use of underlying hardware. This work presents quantitative and qualitative analyses of how software has evolved to reap the benefits of multi-core and heterogeneous computers, compared to state-of-the-art systems in 2000 and 2010. We study a wide spectrum of commonly-used applications on a state-of-the-art desktop machine and analyze two important metrics, Thread-Level Parallelism (TLP) and GPU utilization. We compare the results to prior work over the last two decades, which state that 2–3 CPU cores are sufficient for most applications and that the GPU is usually under-utilized. Our analyses show that the harnessed parallelism has improved and emerging workloads show good utilization of hardware resources. The average TLP across the applications we study is 3.1, with most applications attaining the maximum instantaneous TLP of 12 during execution. The GPU is over-provisioned for most applications, but workloads such as cryptocurrency mining utilize it to the fullest. Overall, we conclude that the effectiveness of software in utilizing the underlying hardware has improved, but still has scope for optimizations.
Generalizing Gender: Reason and Essence in the Legal Thought of Catherine Mackinnon

Catharine MacKinnon's work has been a shaping force in the development of feminist legal theory as well as on the course of legal reform. Although few feminist scholars accept her views on gender and sexuality in their entirety, her preeminent contribution to feminist legal theory is generally acknowledged. MacKinnon's most signal legal reform success has been in identifying sexual harassment as a form of sex discrimination prohibited by federal employment law. More recently, attended by greater controversy and less material success, she has been active in the feminist antipornography campaign. This chapter has two objectives. The first is simply the journeywoman task of understanding MacKinnon's theory of gender and especially the methodology she employs. The second objective is to defend an aspect of MacKinnon's methodology that has of late come under political and philosophical attack. She has been accused of gender essentialism, a vice that is variously defined but is most commonly understood to mean treating the concept of gender as a transcultural and transhistorical universal. The price of gender essentialism, according to its critics, is the imposition of false uniformity on the disparate experience of women of different classes, races, ethnicities, and sexual orientations. Privileged white intellectuals read their own experience as that of women as such. In doing so we falsify the experience of those whom we call sisters but whose voices we ignore. In my view, these deplorable consequences do not necessarily overtake the theorist who seeks to generalize about gender. The impulse that animates MacKinnon's work, the desire to formulate a theory that speaks from and to the experience of all women, should not be easily relinquished. Generalizing about gender, at least in the modest form in which it is done by this bold theorist, need not be philosophically or politically pernicious.
Abstract 2620: Global epigenetic regulation of gene expression and tumor suppression in T-cell leukemia by Ikaros

Ikaros encodes a DNA-binding zinc finger protein that functions as a tumor suppressor. Loss of Ikaros function results in the development of high-risk B-cell and T-cell acute lymphoblastic leukemia. Previous studies suggested that Ikaros controls expression of its target genes via chromatin remodeling, and by forming complexes with the histone deacetylase, HDAC1. However, the mechanisms through which Ikaros regulates the global epigenetic signature in leukemia is unknown. We studied the role of Ikaros in regulating tumor suppression in Ikaros-defficient T-cell acute lymphoblastic leukemia (T-ALL) cells. The re-introduction of Ikaros at physiological levels via retroviral transduction into T-ALL cells, results in a cessation of cellular proliferation and cell cycle arrest within 4 days. To determine the dynamics of Ikaros-mediated epigenetic regulation of gene expression in T-ALL, we performed ChIP-seq of Ikaros, HDAC1, and histone modifications, along with microarray and ATAC-seq in wild-type T-ALL (that lacks Ikaros), and during each of 3 days following the re-introduction of Ikaros. Our results demonstrated that Ikaros directly regulates the global epigenomic landscape including genome wide de novo formation of enhancers in T-ALL. Further analysis showed that Ikaros induces the re-distribution of HDAC1 via direct recruitment of HDAC1 to promoter and enhancer regions of different target genes resulting in their transcriptional repression. Expression analysis identified a large number of novel signaling pathways that are directly regulated by Ikaros and HDAC1, and are responsible for the cessation of proliferation and the cell cycle arrest of T-ALL cells. Our results identified novel functions of Ikaros in the epigenetic regulation of gene expression and tumor suppression in T-ALL. Citation Format: Yali Ding, Bo Zhang, Jonathon L. Payne, Kimberly J. Payne, Chunhua Song, Chandrika Gowda, Soumya Iyer, Pavan K. Dhanyamraju, Dhimant Desai, Suming Huang, Feng Yue, Sinisa Dovat. Global epigenetic regulation of gene expression and tumor suppression in T-cell leukemia by Ikaros [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2620.
Identification of the pathway of iontophoretic drug delivery: light and ultrastructural studies using mercuric chloride in pigs.

Although electrically assisted transdermal drug delivery has recently achieved a great deal of research attention, the precise anatomical pathway followed by these drugs through the stratum corneum has not been clearly defined. Pigs are an accepted model for studying iontophoretic drug delivery in humans. The purpose of this investigation was to visualize the pathway of ion transport by iontophoresing mercuric chloride. Weanling Yorkshire swine were dosed with 7.4% mercuric chloride in the positive electrode at a current density of 200 µAmp/cm2 applied for 1 hr. Biopsies were immediately taken, exposed to 25% ammonium sulfide vapor to precipitate and localize the mercury, fixed, and processed for light and transmission electron microscopy. The presence of mercury, which appeared as a black precipitate, was confirmed using energy-dispersive X-ray microanalysis. Although some compound penetrated the skin through appendageal pathways, the electron micrographs clearly revealed that mercuric chloride traversed the intact stratum corneum via an intercellular route. Precipitate was also localized in the outer membrane of the mitochondria in the viable epidermal cells, dermal fibroblasts, and capillaries, demonstrating transdermal delivery and systemic exposure to the mercury. These findings have implications for iontophoretic drug delivery, since they allow visualization of the functional “pores” predicted by mathematical models.
Nutrients mitigate the impacts of extreme drought on plant invasions.

Extreme climate events, such as drought, are becoming increasingly important drivers of plant community change, yet little is known about their impacts on invasive plants. Further, drought impacts may be altered by other anthropogenic stressors, such as eutrophication. We found drought dramatically reduced density of invasive Lepidium latifolium in salt marshes, and this die-back was mitigated by nutrient addition. In a 3-yr field experiment (2014-2016) conducted during an unprecedented drought (2012-2015), we tracked the effects of drought and nutrient addition on the plant community. We conducted this research at four salt marshes across a salinity gradient in the San Francisco Bay, California, USA. We manipulated paired native and invaded plots, one-half of which were treated monthly with N and P for 1.5 yr during the most intense period of the drought and one subsequent wet winter. In addition, we monitored unmanipulated L. latifolium-invaded transects within our freshest and most saline sites throughout the three years of our manipulative experiment and one additional wet winter. We documented a dramatic die-back of invasive L. latifolium during extreme drought, with reductions in stem density (52-100%) and height (17-47%) that were more severe at low salinity sites than high salinity sites. We found nutrient application lessened the effect of drought on L. latifolium stem density, but not height. In native plots, extreme drought reduced native plant cover (4-24%), but nutrient addition mitigated this impact. Interestingly, native plants in invaded plots did not suffer reductions in cover due to drought, perhaps because they were simultaneously benefiting from the die-back of the invader. Our results show drought negatively impacted both native and invasive plants and this impact was stronger on the invader, which experienced persistent declines two years after the end of the drought. However, by mitigating the effect of drought on invasive plants, nutrient addition potentially erased the advantage drought provided native plants over invasive plants under ambient nutrient conditions.
Why Does the Indian State Both Fail and Succeed

The Indian state's performance spans the spectrum from woefully inadequate, especially in core public goods provision, to surprisingly impressive in successfully managing complex tasks and on a massive scale. It has delivered better on macroeconomic rather than microeconomic outcomes, where delivery is episodic with inbuilt exit than where delivery and accountability are quotidian and more reliant on state capacity at local levels, and on those goods and services where societal norms on hierarchy and status matter less than where they are resilient. The paper highlights three reasons for these outcomes: under-resourced local governments, the long-term effects of India's "precocious" democracy, and the persistence of social cleavage. However, claims that India's state is bloated in size and submerged in patronage have weak basis. The paper concludes by highlighting a reversal of past trends in that state capacity is improving at the micro level even as India's macro performance has become more worrisome.
Using Feedback on Symptomatic Infections to Contain the Coronavirus Epidemic: Insight from a SPIR Model

Abstract A study is presented on the use of real-time information about symptomatic infectious individuals to adjust restrictions of human contacts at two basic levels, the stricter being on the symptomatic infectious group. Explicit analytical formulas as well as numerical results are presented to rapidly elucidate what-if questions on averting resurgence of the coronavirus epidemic after the first wave wanes. Implementation of related ideas would rely on a mix of several factors, including personal initiative and sophisticated technology for monitoring and testing. For robust decision making on the subject, detailed multidisciplinary studies remain indispensable.
A Systematic Study on BEOL Defectivity Control for Future AI Application

In this paper, a case study on control of BEOL defectivity in a systematic way for the future AI application is presented. A few novel methodologies were introduced to identify the source of defectivity in various BEOL sectors, such as, patterning, barrier deposition, plating, and CMP. We successfully reduced the defectivity to the level required to yield target AI devices.
Contracting in the shadow of a corrupt court

This paper presents an incomplete contracting model to show how judicial corruption and judicial favoritism can lead to distortions in agents' incentives to invest in relation-specific assets and cause inefficiency. I also show that while an increase in the judge's income always increases investment, it is possible that a strongly favoritism-reducing increase in the authority's propensity to monitor the judiciary can actually reduce, instead of increase, investment in equilibrium. The implications of these findings for the study of institutional reforms, the relationship between the institutional environment and institutional arrangements, and the political economy of connections are explored.