cssi/SciSciGPT-SciSciNet huggingface dataset:
Crustacean neuroendocrine systems and their signaling agents

Decapod crustaceans have long served as important models for the study of neuroendocrine signaling. For example, the process of neurosecretion was first formally demonstrated by using a member of this order. In this review, the major decapod neuroendocrine organs are described, as are their phylogenetic conservation and neurochemistry. In addition, recent advances in crustacean neurohormone discovery and tissue mapping are discussed, as are several recent advances in our understanding of hormonal control in this group of animals.
Using Fingerprint Authentication to Reduce System Security: An Empirical Study

Choosing the security architecture and policies for a system is a demanding task that must be informed by an understanding of user behavior. We investigate the hypothesis that adding visible security features to a system increases user confidence in the security of a system and thereby causes users to reduce how much effort they spend in other security areas. In our study, 96 volunteers each created a pair of accounts, one secured only by a password and one secured by both a password and a fingerprint reader. Our results strongly support our hypothesis -- on average. When using the fingerprint reader, users created passwords that would take one three-thousandth as long to break, thereby potentially negating the advantage two-factor authentication could have offered.
Mechanisms of Enhanced Vascular Reactivity in Preeclampsia

Preeclamptic women have enhanced blood pressure response to angiotensin II and extensive systemic vascular infiltration of neutrophils. Neutrophils release reactive oxygen species that might activate the RhoA kinase pathway to enhance vascular reactivity. We hypothesized that enhanced vascular reactivity in preeclampsia is attributed to neutrophil-mediated reactive oxygen species activation of the RhoA kinase pathway. Omental arteries were obtained at cesarean section and studied using a myograph system. We found that arteries of preeclamptic women had extensive infiltration of neutrophils and enhanced reactivity to angiotensin II. Treatment of arteries of normal pregnant women with reactive oxygen species or activated neutrophils enhanced vessel reactivity to angiotensin II mimicking preeclamptic vessels. Pretreatment with superoxide dismutase/catalase to quench reactive oxygen species or RhoA kinase inhibitor blocked enhanced responses in preeclamptic and normal vessels. Reactive oxygen species also enhanced vessel reactivity to norepinephrine, which was blocked by RhoA kinase inhibition. Treatment of arteries with reactive oxygen species increased RhoA kinase activity 3-fold, whereas culture of human vascular smooth muscle cells with angiotensin II and activated neutrophils or reactive oxygen species resulted in phosphorylation of key proteins in the RhoA kinase pathway. We conclude that enhanced vascular reactivity of omental arteries in preeclampsia is attributed to reactive oxygen species activation of the RhoA kinase pathway and that enhanced vascular reactivity is likely attributed to the infiltration of neutrophils. We speculate that neutrophil infiltration into systemic vasculature of preeclamptic women is an important mechanism for hypertension.
Experimental investigation of human and machine-vision arrangements in inspection tasks

Abstract The traditional job of a quality control inspector, whether human or a machine-vision device, is to discriminate products into acceptable and non-acceptable items. The performance of inspectors can be measured in terms of rejecting non-acceptable items (Type I error) or classifying non-acceptable items as acceptable (Type II error). Reinspection is often used afterward to remedy this situation if required. Unfortunately, all such inspections remain prone to errors. This paper uses an experimental investigation to research the various ways in which the positive attributes of human and machine-vision inspection systems can be arranged to achieve enhanced system performance in industrial inspection tasks.
Estimation of Capacitive Crosstalk-Induced Short-Circuit Energy

In the nanometer regime, crosstalk significantly impacts the dynamic power consumption of a chip. In this paper, we present a methodology for analyzing crosstalk-induced short-circuit power dissipation in cell-based digital designs. We introduce a new cell pre-characterization technique for facilitating the estimation of crosstalk-induced short-circuit power. Examples demonstrate that the presented methodology is three orders of magnitude faster than circuit simulators while the average error is as low as 3.5%.
Children's moral reasoning and their perceptions of television violence

This experiment examined the effect of a child's age on his or her interpretation of an act of interpersonal violence on television. One hundred eighty-four children in 2 age groups were randomly assigned to 1 of 4 viewing conditions in which they watched a violent video clip. The clips depicted identical violent acts; however, punishment (yes/no) of the violent act and provocation (yes/no) for the violent act were manipulated to create the 4 conditions. Following the video clip, children were asked to judge whether the act was right or wrong and why. They then engaged in a test of their willingness to choose aggression as a solution to a hypothetical interpersonal conflict. As predicted, younger children thought that unpunished violence was more right than punished violence. Older children thought that provoked violence was more right than unprovoked violence, although this result only approached significance. Children's willingness to choose a violent story ending to a hypothetical interpersonal conflict was related to their experimental condition for older children but not for younger children.
NF‐κB protects from the lysosomal pathway of cell death

The programme of gene expression induced by RelA/NF‐κB transcription factors is critical to the control of cell survival. Ligation of ‘death receptors’ such as tumor necrosis factor receptor 1 (TNF‐R1) triggers apoptosis, as well as NF‐κB, which counteracts this process by activating the transcription of anti‐apoptotic genes. In addition to activating caspases, TNF‐R1 stimulation causes the release of cathepsins, most notably cathepsin B, from the lysosome into the cytoplasm where they induce apoptosis. Here we report a mechanism by which NF‐κB protects cells against TNF‐α‐induced apoptosis: inhibition of the lysosomal pathway of apoptosis. NF‐κB can protect cells from death after TNF‐R1 stimulation, by extinguishing cathepsin B activity in the cytosol. This activity of NF‐κB is mediated, at least in part, by the upregulation of Serine protease inhibitor 2A ( Spi2A ), a potent inhibitor of cathepsin B. Indeed, Spi2A can substitute for NF‐κB in suppressing the induction of cathepsin B activity in the cytosol. Thus, inhibition of cathepsin B by Spi2A is a mechanism by which NF‐κB protects cells from lysosome‐mediated apoptosis.
Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells

A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products. Pathogen-induced host cell death has been characterized as apoptosis in many of these systems. It is increasingly being
Caveolin-1 Upregulation Contributes to c-Myc–Induced High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer

Previously we reported caveolin-1 (Cav-1) overexpression in prostate cancer cells and showed that it promotes prostate cancer progression. Here, we report that Cav-1 was overexpressed in 41.7% (15 of 36) of human high-grade prostatic intraepithelial neoplasia (HGPIN) specimens obtained during radical prostatectomies. Positive correlations exist between Cav-1-positive (Cav-1(+)) HGPIN and Cav-1(+) primary prostate cancer (rho = 0.655, P < 0.0001) and between Cav-1 and c-Myc expression in HGPIN (rho = 0.41, P = 0.032). To determine whether Cav-1 cooperates with c-Myc in development of premalignant lesions and prostate cancer in vivo, we generated transgenic mice with c-Myc overexpression driven by the ARR(2)PB promoter. In this ARR(2)PB-c-myc model, Cav-1 overexpression was found in mouse PIN (mPIN) lesions and prostate cancer cells and was associated with a significantly higher ratio of proliferative to apoptotic labeling in mPIN lesions than in the Cav-1-negative epithelia adjacent to those lesions (10.02 vs. 4.34; P = 0.007). Cav-1 overexpression was also associated with increased levels of P-Akt and VEGF-A, which were previously associated with Cav-1-induced prostate cancer cell survival and positive feedback regulation of cellular Cav-1 levels, respectively. In multiple prostate cancer cell lines, Cav-1 protein (but not mRNA) was induced by c-Myc transfection, whereas VEGF siRNA transfection abrogated c-Myc-induced Cav-1 overexpression, suggesting a c-Myc-VEGF-Cav-1 signaling axis. Overall, our results suggest that Cav-1 is associated with c-Myc in the development of HGPIN and prostate cancer. Furthermore, Cav-1 overexpression in HGPIN is potentially a biomarker for early identification of patients who tend to develop Cav-1(+) primary prostate cancer.
Teledermatology: current concepts and future directions

Teledermatology refers to the use of technology to exchange dermatologic information. The demand for dermatologic care continues to grow rapidly, while the ability to deliver it is relatively static. In a world of scarce dermatologic resources and significant demand, teledermatology offers a relatively economical option for improving access to diagnostically reliable and accurate dermatologic care. Current teledermatologic research is focused on better understanding the quality of teledermatologic care as compared with standard methods of care delivery. This article examines teledermatology, from its origins, to its ‘present’, including recent studies examining the quality of teledermatologic care as well as the variety of ways in which this technology is being employed. Finally, it discusses the bright future of teledermatology and the directions it may take.
CONSTITUTIONALISM IN THE AGE OF TERROR

The threat of terrorism once again raises some of the classic questions about constitutionalism: is it possible for constitutions to do what they aim to do—channel and control political power in such a way as to make it safe and beneficent for those under its rule but also competent to govern? Does not terrorism reraise the Schmittian problem of “the exception”, i.e., the situation of emergency that necessarily escapes all constitutional limitations? Although they did not face the problem of terrorism as we know it, the American founders developed three different models of constitutionalism, embodying three different ways of responding to emergent circumstances and yet remaining bound to the constitutionalist aspiration. We develop the main outlines of the three models both conceptually and historically and show how they continue to be relevant to current discussions of constitutionalism in the age of terror. Finally, we make a tentative effort to judge which of the three models is most able to do what constitutions should do in difficult times.
"How Would That Help Our Work?": The Intersection of Domestic Violence and Human Rights in the United States

This qualitative study explores whether individuals working within the domestic violence (DV) field in the United States have utilized a human rights framework and identifies potential benefits of this framework. Using the critique and experiences of women of color as a focal point, data were gathered through interviews with key individuals working with national and regional DV and human rights organizations. This article focuses on challenges within the mainstream DV movement and how a human rights approach could potentially ameliorate some of these concerns by supporting a more holistic approach to DV and increasing coalition building and community engagement.
Reevaluating the Effects of Redistricting on Electoral Competition, 1972-2012

In this note, we revisit the work of Carson and Crespinto examine the effect of different redistricting plans on competitiveness in U.S. House elections. Similar to the previous results, our probit estimates on an expanded dataset that includes redistricting cycles from 1972 to 2012 reveal that commission and court-drawn districts experience more competition on average than those drawn by legislatures. These results provide additional support for the hypothesis that one way to increase the competitiveness of congressional elections is to allow extra-legislative bodies to draw congressional district boundaries.
A Practical System For Business Ethics

This paper presents a model for behavior that is culturally neutral and virtually universally acceptable in a multicultural society.
PRACTITIONERS' CORNER A Note on the Selection of Time Series Models

We consider issues related to the order of an autoregression selected using information criteria. We study the sensitivity of the estimated order to (i) whether the effective number of observations is held fixed when estimating models of different order, (ii) whether the estimate of the variance is adjusted for degrees of freedom, and (iii) how the penalty for overfitting is defined in relation to the total sample size. Simulations show that the lag length selected by both the Akaike and the Schwarz information criteria are sensitive to these parameters in finite samples. The methods that give the most precise estimates are those that hold the effective sample size fixed across models to be compared. Theoretical considerations reveal that this is indeed necessary for valid model comparisons. Guides to robust model selection are provided.
Improving the design and reliability of future computer systems via using intermediate values of outputs

In future computer systems, we will need to increase the utilization ratio of existing hardware and software modules to achieve the desired efficiency of maximum speed, minimum power usage, and improved reliability. In typical hardware and software modules, once the inputs of the system are ready, the final values of the outputs become available after a certain amount of time (called execution time in software and delay in hardware). While a module is computing the output values, it is often considered as a black box and often we do not have access to intermediate results produced by the module. In this paper, we explore the utilization of intermediate values generated by hardware and software modules in order to improve future computer systems. For modules that do not produce intermediate values, we need to establish techniques to redesign the modules so that they produce useful intermediate values. By using the available/generated intermediate values, we can produce faster computer systems with less power usage. Moreover, the reliability of computer systems (test, verification, and fault tolerance) can be also improved. We present case studies and preliminary simulation results that show that our technique of utilizing intermediate values is highly effective, feasible, and promising.
Cytodiagnosis of malignant melanoma. Immunoperoxidase staining with HMB-45 antibody as an aid to diagnosis.

The specificity and sensitivity of HMB-45, an antimelanoma monoclonal antibody, was evaluated in cytologic specimens from extracutaneous melanomas. Melanoma cells in 23 of 25 (92%) cases stained with this antibody. Staining was intense and diffuse in 22 of these melanomas and focal in 1. Amelanotic tumors and tumors with scanty pigment were included. Neither degree of pigmentation, site of primary, cytologic characteristics of tumor, nor source of specimen predicted the immunostaining pattern. Cytopreparations containing benign (6 cases) and malignant (16 cases) cells with which melanoma may be confused constituted the nonmelanoma group. None of the 22 cases in this group stained. Undifferentiated carcinomas, adenocarcinomas, large cell lymphomas, sarcomas, mesothelial hyperplasias, and a benign nerve sheath tumor were included. Effusions, fine-needle aspirates, bronchial material, and imprints were studied. All smears had been fixed and stained by Papanicolaou’s method before immunostaining. Excellent cytomorphologic characteristics were preserved, and immunostaining was not affected. HMB-45 antibody is a highly specific and sensitive marker for malignant melanoma in cytologic material.
An Archaeological Survey and Monitoring of the Razing of the Acuna Furniture and Music Company Building, Downtown San Antonio, Texas

In September 1985, the Center for Archaeological Research, The University of Texas at San Antonio, was requested to conduct an investigation of the archaeological potential of the Acuna Furniture and Music Company building located at 125 North Flores Street, San Antonio, Texas. An archival search, to determine the construction period of the present building and possible prior structures, was conducted, and an on-site inspection was made. Both indicated that no historic resources would be affected by the demolition of the building. The demolition of the building was monitored to assure that no artifacts were revealed. No further work is recommended at this time.
Predictors of quality of life in patients with advanced heart failure awaiting transplantation.

Background: Quality of life is an important outcome to measure in patients with end-stage heart disease who are awaiting heart transplantation. The purposes of this study were threefold: (1) to assess life satisfaction in multiple areas, (2) to examine correlations between life satisfaction and demographic, physiologic, and psychosocial variables, and (3) to identify predictors of quality of life in patients with advanced heart failure who were awaiting heart transplantation. Methods: Data were collected from a convenience sample of 359 adult heart transplant candidates from a midwestern and a southern medical center. Eight instruments were used to gather data from patients. All tools had adequate psychometric support. Data were analyzed by using descriptive statistics, Pearson correlations, and stepwise multiple regression analysis. Results: Results showed that patients were most satisfied with significant others (e.g., emotional support from others, children, and family's health) and least satisfied with their health and functioning (e.g., current health status, ability to travel, and energy for daily activities). Significant correlations were found between total life satisfaction and age, New York Heart Association Functional classification, total number of daily medications, functional disability, symptom distress, stress, coping, helpfulness of heart transplant team interventions, health perception, expectation of transplant success, and overall quality of life. Conclusions: Eleven of 19 variables were significant predictors of higher quality of life in patients with advanced heart failure awaiting heart transplantation and accounted for 49% of explained variance: less symptom distress, better health perception, greater helpfulness of heart transplant team interventions, less stress, better coping ability, less functional disability, less use of fatalistic coping, older age, greater effectiveness of optimistic coping, being unemployed, and the expectation of transplant success
The Case For Ethical Rightness

"Oboy, Oboy," a critical study which dares to grapple with a critically unpopular though not insignificant idea: the determination of ethical rightness in fiction. At a time when literary critics question the validity of ascribing meaning, Truth, or morality to fiction, when philosophers explore the ability or lack of ability of language to convey meaning, and when science suggests that the notions of Truth and reality are at root far more paradoxical and problematic than they once may have seemed, Brian Stonehill's The Self-Conscious Novel: Artifice in Fiction from Joyce to Pynchon takes an admirable risk. In examining the combination of "esthetic neatness and ethical rightness" in modern and contemporary self-reflexive novels, Stonehill sets out to prove that self-consciousness, far from being merely self-indulgent and meaningless, "may in fact be one of the most convincing and compelling forms available to our writers for the expression of what is truly important today" (18).
Surgical management of traumatic frontal sinus fractures: Case series from a single institution and literature review

Background: Neurosurgeons are frequently involved in the management of patients with traumatic frontal sinus injury; however, management options and operative techniques can vary significantly. In this study, the authors review the current literature and retrospectively review the clinical series at a single tertiary referral center. Methods: After Institutional Review Board approval, the medical records and computed tomographic (CT) imaging of patients whose traumatic frontal sinus fractures were treated surgically at the University of Utah were retrospectively reviewed. Demographic information, mechanism of injury, associated injuries, operative technique, and pattern of injury on CT were analyzed. Results: Between 2000 and 2012, 33 patients underwent successful cranialization of the frontal sinus following traumatic injury. The material used to obliterate the sinus varied. No patients required immediate or delayed reoperation. Nasofrontal outflow tract obstruction, the importance of which has been emphasized in the plastic surgery literature, was apparent on either initial or retrospective review of the available CT imaging in 96%. Conclusions: In this series, we successfully surgically treated 33 patients with frontal sinus fractures. The presence of cerebrospinal fluid leak, nasofrontal outflow tract injury, associated depressed skull fractures, and subsequent formation of communicating pathways and infection must be considered when constructing a treatment plan. The goals of treatment should be: (i) surgical repair of the defect and elimination of the conduit from the intracranial space to the outside and (ii) elimination of any cerebrospinal fluid pressure gradient that may develop across the surgical repair. We present a treatment algorithm focusing on the presence of nasofrontal outflow tract injury/obstruction, cosmetic deformity, and cerebrospinal fluid leak.
Grinding wheel motion, force, temperature, and material removal in rotational atherectomy of calcified plaque

Abstract This study investigates the grinding wheel motion, force, material removal, and temperature in rotational atherectomy (RA). RA utilizes a metal-bond diamond wheel to remove plaque from arteries to treat cardiovascular diseases. As a plaque surrogate, a bone workpiece was placed in a vessel simulator and subjected to RA with a wheel rotational speed of 160,000 rpm. This grinding process was monitored by a high-speed camera, a dynamometer, and embedded thermocouples. The results show this process has a 108 Hz wheel orbital frequency, an oscillating grinding force of 0.23 N, 90% debris smaller than 31 μm, and a 4.1 °C temperature rise.
Effects of nitrate or nitro supplementation, with or without added chlorate, on Salmonella enterica serovar Typhimurium and Escherichia coli in swine feces.

The effects of coincubating the active agent of an experimental chlorate product with nitrate or select nitro compounds, possible inducers and competing substrates for the targeted respiratory nitrate reductase, on concentrations of experimentally inoculated Salmonella enterica serovar Typhimurium and indigenous Escherichia coli were determined. Studies were completed in swine fecal suspensions as a prelude to the administration of these inhibitors to pigs. Results confirmed the bactericidal effect of chlorate (5 to 10 mM) against these fecal enterobacteria, reducing (P 2 log CFU ml(-1) after 3 to 6 h of incubation. An effect (P < 0.05) of pH was observed, with considerable regrowth of Salmonella and E. coli occurring after 24 h of incubation in suspensions buffered to pH 7.1 but not in suspensions buffered to pH 6.5 or 5.6. A 24-h coincubation of fecal suspensions with 5 to 10 mM chlorate and as little as 2.5 mM nitrate or 10 to 20 mM 2-nitro-1-propanol, 2-nitroethanol, and, sometimes, nitroethane decreased (P < 0.05) Salmonella but not necessarily E. coli concentrations. 2-Nitro-1-propanol and 2-nitroethanol exhibited inhibitory activity against Salmonella and E. coli by an undetermined mechanism, even in the absence of added chlorate.
Mesoscale studies of ionic closed membranes with polyhedral geometries

Large crystalline molecular shells buckle spontaneously into icosahedra while multicomponent shells buckle into various polyhedra. Continuum elastic theory explains the buckling of closed shells with one elastic component into icosahedra. A generalized elastic model, on the other hand, describes the spontaneous buckling of inhomogeneous shells into regular and irregular polyhedra. By co-assembling water-insoluble anionic (−1) amphiphiles with cationic (3+) amphiphiles, we realized ionic vesicles. Results revealed that surface crystalline domains and the unusual shell shapes observed arise from the competition of ionic correlations with charge-regulation. We explain here the mechanism by which these ionic membranes generate a mechanically heterogeneous vesicle.
Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer.

Background Pancreatic cancer is characterised by the accumulation of a fibro-inflammatory stroma. Within this stromal reaction, myeloid cells are a predominant population. Distinct myeloid subsets have been correlated with tumour promotion and unmasking of anti-tumour immunity. Objective The goal of this study was to determine the effect of myeloid cell depletion on the onset and progression of pancreatic cancer and to understand the relationship between myeloid cells and T cell-mediated immunity within the pancreatic cancer microenvironment. Methods Primary mouse pancreatic cancer cells were transplanted into CD11b-diphtheria toxin receptor (DTR) mice. Alternatively, the iKras* mouse model of pancreatic cancer was crossed into CD11b-DTR mice. CD11b + cells (mostly myeloid cell population) were depleted by diphtheria toxin treatment during tumour initiation or in established tumours. Results Depletion of myeloid cells prevented Kras G12D -driven pancreatic cancer initiation. In pre-established tumours, myeloid cell depletion arrested tumour growth and in some cases, induced tumour regressions that were dependent on CD8 + T cells. We found that myeloid cells inhibited CD8 + T-cell anti-tumour activity by inducing the expression of programmed cell death-ligand 1 (PD-L1) in tumour cells in an epidermal growth factor receptor (EGFR)/mitogen-activated protein kinases (MAPK)-dependent manner. Conclusion Our results show that myeloid cells support immune evasion in pancreatic cancer through EGFR/MAPK-dependent regulation of PD-L1 expression on tumour cells. Derailing this crosstalk between myeloid cells and tumour cells is sufficient to restore anti-tumour immunity mediated by CD8 + T cells, a finding with implications for the design of immune therapies for pancreatic cancer.
An unlikely union: the love-hate story of New York's Irish and Italians

This historical narrative by Paul Moses – a prize-winning author and journalist – is an investigation of the mostly contentious relationship between the Irish and Italian ethnic groups in New York ...
DDEL-03INTRAVENOUS NANOPARTICLE DELIVERY TO GLIOBLASTOMA

A major obstacle in the treatment of glioblastoma (GBM) is the blood brain barrier (BBB), which restricts drug molecules in the bloodstream from reaching the tumor. The BBB may be disrupted at or near the GBM tumor core, but it is intact at the growing edge of the tumor, where invasive cells reside and can cause disease recurrence. To combat GBM more effectively, novel drug transport technology that crosses intact BBB is urgently needed. Brain microvascular endothelial cells (BMEC) found in the BBB are lined with low-density lipoprotein receptors (LDLr) and LDL-like receptor proteins (LRP), which are essential to the endocytosis/ transcytosis processes of BMEC. GBM cells are known to express higher levels of LDLr and LRP than normal brain cells. The objective of our research is to develop a novel lipid nanoparticle (NP) that targets LDLr and LRP to facilitate BMEC endocytosis/ transcytosis and GBM uptake. We focused on developing antisense oligonucleotides (oligos) as the drug cargo for our NP. Less than 20% of disease-associated genes are targetable by conventional drug molecules; however, we hypothesize that disease-associated genes, like EZH2 and ZEB1 transcriptional repressors, are amendable to antisense oligo inhibition. We engineered a novel NP which is composed of neutral lipids: phosphatidylcholine (PC), cholesterol (Chol) and a polymer called poloxamer (PXR). Toxicology studies indicated that NP composed of PC/Chol/PXR did not have adverse effects on mice. Flow cytometry and fluorescent microscopy revealed that PC/Chol/PXR NP was avidly taken up by BMEC, and that PC/Chol/PXR efficiently delivered antisense oligos to GBM cells. Additionally, intravenous injection of PC/Chol/PXR led to deposition of antisense oligos in intracranial GBM xenografts. Future studies will determine the efficacy of the innovative PC/Chol/PXR NP in suppressing target gene expression in intracranial GBM. (Supported by Florida Center for Brain Tumor Research and Accelerate Brain Cancer Cure).
Third Generation Chimeric Antigen Receptors Containing CD137 or CD134 Signaling Endodomains Augment CD19-Specific T-Cell Effector Function.

Abstract 4097 Poster Board III-1032 CD19-specific chimeric antigen receptors (CARs) based on first and second generation designs (Figure) expressed by genetically manipulated T cells are being evaluated in clinical trials and it is apparent that the long term in vivo survival of the infused T cells will be critical to achieving therapeutic successes. We have previously demonstrated that the first-generation CAR can be modified to include and provide an improved T-cell survival signal through addition of a chimeric CD28 endodomain (designated second generation CAR, CD19RCD28). However, it is recognized that optimal activation of T cells through CD28 for sustained proliferation may require co-stimulation through other signaling molecules. To address this issue we have altered the second generation CAR to include additional intracellular signal transduction domains from CD137 (4-1BB) or, CD134 (OX40) to generate (Figure) third generation CARs (CD19RCD28CD137 or, CD19RCD28CD134, respectively). The third generation CARs were electro-transferred into peripheral blood T cells using the Sleeping Beauty transposon/transposase system and propagated on K562-derived CD19+ artificial antigen presenting cells (aAPCs). We observed the selective outgrowth of CD19-specific T cells expressing similar percentages of expression and densities of CD19RCD28, CD19RCD28CD137, and CD19RCD28CD134 CARs with a subset of the propagated T cells displaying a central memory phenotype (CD62L+CD28+). The T cells expressing the third generation CARs exhibited redirected-killing and were able to produce IFN-g in response to CD19. Although the cytolytic ability and Tc1 cytokines released by both second and third generation CARs were similar, differences due to the presence of the CD137 and CD134 intracellular signaling endodomains were apparent using in vitro experiments designed to mimic in vivo T-cell persistence, by measuring long-term propagation in the absence of exogenous cytokines added to the T-cell culturing process. We observed an approximate 200% increase in the numeric expansion of CD19RCD28CD137+ and CD19RCD28CD134+ T cells as compared to the CD19RCD28+ T cells at the end of 14 days of co-culture on CD19+ aAPC. These data highlight the fact that CD19-dependent signaling through chimeric CD28 might be improved by the addition of signaling through chimeric CD137 or CD134 domains so as to fully maintain T-cell activation and sustain proliferation in vivo after adoptive transfer. Disclosures: No relevant conflicts of interest to declare.
Non-invasive Measures of Core Temperature versus Ingestible Thermistor during Exercise in the Heat.

The accuracy of core temperature (Tc) thermometry from temporal, tympanic, and oral thermometry devices has been variable during exercise in a hot, humid environment. The purpose of the present study was to cross-validate temporal, two tympanic devices, and oral devices compared to an ingestible thermistor during exercise in a hot, humid environment. Fourteen young, active adults (6 women) completed a graded exercise test until voluntary exhaustion in an environmental chamber (35.5 ± 0.6 °C, 53.9 ± 5.8 % RH). There was no statistical difference in mean temperature between tympanic device 1 and pill-based core temperature (PBTc) measurements across all time points and were positively correlated (0.357; P<0.001). Temperatures of tympanic device 2 were statistically higher than PBTc (37.8 ± 0.7 oC vs. 37.6 ± 1.0 oC; respectfully) (P=0.008). At all time points, temperatures for the second tympanic device and PBTc were positively correlated (0.192; P=0.043). Temporal and PBTc values did not differ across time points and were positively correlated (0.262; P=0.005) across all time points. Mean oral temperature was significantly less than mean PBTc across all time points. (37.0 ± 0.4 oC vs. 37.6 ± 1.0 oC, respectively) (P<0.001). Across all time points, oral and PBTc were positively correlated (0.262; P=0.010). Tympanic and temporal devices can reflect Tc while exercising in a hot, humid environment. However, care should be taken when selecting the tympanic or temporal measurement device and validation is advised prior to heat illness mitigation in the field.
Technology Assessment in the Automotive Sector

Innovation is not a new concept, but the extent to which it is used is. Economies are shifting from industrial based to knowledge based innovation. Innovation has been effectively applied to product and manufacturing process innovation, but with the growth of innovation, more focus is being applied to improve management of innovation and information to effectively introduce the volume of innovation. This includes processes and tools used to manage innovation. Finally innovation is being applied to all areas and operations of businesses. Application of innovation to all parts of a business has been recognized as a crucial element to remain competitive.
Cord Blood Transplants for Lymphoid Malignancies in Adults

Umbilical cord blood transplantation (UCBT) has emerged as a viable treatment strategy for patients with high-risk lymphoid malignancies such as acute lymphoblastic leukemia and advanced mature lymphoproliferative disorders. Donor-derived, immune-mediated graft-versus-tumor responses may result in long-term disease control and potential cure. Because of the proliferative potential of UCB hematopoietic cells, the UCB cell dose can be nearly ten times lower than the dose used for peripheral blood transplants; however, the number of cells obtained with a single UCB unit is limited, and double UCB unit transplants are often required for adults. We review the data on the use of UCBT in acute lymphoblastic leukemia in adults and the extended use of reduced intensity conditioning UCBT for non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic lymphocytic leukemia.
Investigating coevolutionary archive based genetic algorithms on cyber defense networks

We introduce a new cybersecurity project named RIVALS. RIVALS will assist in developing network defense strategies through modeling adversarial network attack and defense dynamics. RIVALS will focus on peer-to-peer networks and use coevolutionary algorithms. In this contribution, we describe RIVALS' current suite of coevolutionary algorithms that use archiving to maintain progressive exploration and that support different solution concepts as fitness metrics. We compare and contrast their effectiveness by executing a standard coevolutionary benchmark (Compare-on-one) and RIVALS simulations on 3 different network topologies. Currently, we model denial of service (DOS) attack strategies by the attacker selecting one or more network servers to disable for some duration. Defenders can choose one of three different network routing protocols: shortest path, flooding and a peer-to-peer ring overlay to try to maintain their performance. Attack completion and resource cost minimization serve as attacker objectives. Mission completion and resource cost minimization are the reciprocal defender objectives. Our experiments show that existing algorithms either sacrifice execution speed or forgo the assurance of consistent results. rIPCA, our adaptation of a known coevolutionary algorithm named IPC A, is able to more consistently produce high quality results, albeit without IPCA's guarantees for results with monotonically increasing performance, without sacrificing speed.
Why insurgents kill civilians in capital cities: A disaggregated analysis of mechanisms and trends

Abstract Research into the causes of violence against civilians has increased significantly in recent years, yet the mechanisms governing spatial patterns of victimization remain poorly understood. My investigation explores if and why one specific locality, capital cities, experiences a higher frequency of violence against civilians perpetrated by armed insurgent organizations. I argue that the political value associated with capitals allows these groups to asymmetrically impose higher costs on the regime by targeting civilians in these localities. I lay out and validate three specific mechanisms to explain this pattern: elite coercion, popular intimidation, and international persuasion. In the first scenario insurgents aim to influence domestic elites directly. In the second, they aim is to affect domestic civilians’ resolve. In the third, they seek to influence international audiences. Using new geolocated global atrocities data for the years 1996–2009, I evaluate this linkage by employing different methodological approaches and accounting for potential reporting biases. Finally, I show that ethnic and secessionist wars are more likely to experience atrocities in the capital compared with other conflicts. The findings illustrate potential benefits from explaining the temporal and spatial variation in violence by insurgents, with a focus on strategic conditions and power asymmetries.
Unconstitutional limbo: why the Smithsonian Institution may violate the separation of powers doctrine

With the opening of the National Museum of African-American History, people are once again coming in mass to the National Mall to see the Smithsonian’s newest edition. And just about everyone in America knows of the Smithsonian--its name recognition is well over 90% in public surveys. Each year 30 million people visit the Smithsonian museums along the National Mall in Washington, D.C., the National Air and Space Museum, the National Museum of American History, and the National Museum of Natural History among them. But is that about to change? The Smithsonian is an odd government entity. Despite its private, non-profit status, the Smithsonian still receives federal funds, is chartered by an Act of Congress, employs a majority civil service staff, and operates through a board overseen by the Chief Justice of the Supreme Court, the Vice President, and legislators from the United States Senate and Congress. As such, the Smithsonian has been deemed a governmental entity is some instances and a private entity in others. However, with a new bill being introduced to Congress and recent Supreme Court precedent regarding government instrumentalities, the Smithsonian may face dissolution of its current supervisory board less it run the risk of violating the separation of powers doctrine.
Identification of damage in plates using full-field measurement with a continuously scanning laser Doppler vibrometer system

Abstract An effective and reliable damage identification method for plates with a continuously scanning laser Doppler vibrometer (CSLDV) system is proposed. A new constant-speed scan algorithm is proposed to create a two-dimensional (2D) scan trajectory and automatically scan a whole plate surface. Full-field measurement of the plate can be achieved by applying the algorithm to the CSLDV system. Based on the new scan algorithm, the demodulation method is extended from one dimension for beams to two dimensions for plates to obtain a full-field operating deflection shape (ODS) of the plate from velocity response measured by the CSLDV system. The full-field ODS of an associated undamaged plate is obtained by using polynomials with proper orders to fit the corresponding full-field ODS from the demodulation method. A curvature damage index (CDI) using differences between curvatures of ODSs (CODSs) associated with ODSs that are obtained by the demodulation method and the polynomial fit is proposed to identify damage. An auxiliary CDI obtained by averaging CDIs at different excitation frequencies is defined to further assist damage identification. An experiment of an aluminum plate with damage in the form of 10.5% thickness reduction in a damage area of 0.86% of the whole scan area is conducted to investigate the proposed method. Six frequencies close to natural frequencies of the plate and one randomly selected frequency are used as sinusoidal excitation frequencies. Two 2D scan trajectories, i.e., a horizontally moving 2D scan trajectory and a vertically moving 2D scan trajectory, are used to obtain ODSs, CODSs, and CDIs of the plate. The damage is successfully identified near areas with consistently high values of CDIs at different excitation frequencies along the two 2D scan trajectories; the damage area is also identified by auxiliary CDIs.
Solving the Puzzle of Neurodegeneration

Abstract Neurodegenerative disease is a major health problem worldwide. While no effective therapeutics have been developed to slow, halt or prevent any neurodegenerative disease, considerable progress has been made toward identifying pathological biomolecules and mutations associated with familial disease. These findings have stimulated the exploration of hypotheses about the molecular and cellular processes that lead to neurodegeneration. Common themes include protein misfolding and aggregation, insufficient protein clearance, dysfunctional mitochondria and altered energy metabolism, disrupted axonal transport, neuroinflammation, and RNA-mediated toxicity. The transsynaptic spread of pathological protein seeds from neuron to neuron is also emerging as an important common theme with implications for developing therapeutics. Aging is a general risk factor for neurodegenerative diseases, as postmitotic neurons and their unique morphology and function make them especially vulnerable to disrupted cellular homeostasis that occurs with age. A wide variety of animal models have been developed, particular transgenic mice, which provide critical tools to test hypotheses about pathogenic mechanisms and candidate therapeutics. Advances in diagnostics are essential for identifying presymptomatic at-risk individuals and testing agents for prevention, as considerable neurodegeneration has already occurred by the time of disease onset. The prospects for discovering effective therapeutics for these devastating diseases are promising but will require filling in gaps in knowledge, examining assumptions regarding disease mechanisms, and a committing to the exploration of a variety of targets.
Managerial Attitudes Toward the Valuation of Information Technology

As Tom Peters points out, “information is everything” to business organizations in their pursuit of competitive advantage and profitability [Peters, 1992 p. 109]. The intangible aspect of information, however, gives managerial personnel the vague task of placing value on the systems which create, collect, compile, and translate information into a source of profitability. The information systems (IS) literature has dealt with this issue from a quantitative standpoint with varying results [cf Matlin, 1979, West & Courtney, 1993]. However, when senior executives are asked to indicate how information technology expenditures are quantified, they cannot point to a hard measurable quantity that can express the value of the IS [Katz, 1993].
From Premed to US Professor of the Year: My Personal Journey

Mom was always a renaissance woman. Her singing voice was pitch-perfect, and she could play the piano. She could paint and draw, and her artwork was framed throughout the house and featured on t-shirts. She would drag my sister and me into the kitchen to teach us her cooking skills. Her closet was full of the most fashionable shoes, clothing, colorful scarfs, and jewelry. We had a costume drawer filled with costumes she had hand-sewn herself. Despite much resistance from us, she was everyone in the house’s barber. She fixed leaky sinks and changed tires. There was nothing my mom couldn’t do, and if she didn’t know how, she would teach herself, try it out on us, then make us learn how to do it, too.—Mariam El-Ashmawy
Heritage Somali and Identity in Rural Wisconsin

Wisconsin has a long history of heritage language use, which continues to the present. Latinos, Hmong, and Somalis are groups, which now call Wisconsin home. As new generations of American-born individuals emerge, more removed from immigrant culture, the vitality of the language as a heritage language may weaken. This study examines the vitality of Somali as a heritage language in Barron, Wisconsin. It investigates the negotiation of identities in the context of heritage Somali in the rural Upper Midwest.
Digital Asset Planning for Minors

This article is one of the first to explore minors, digital assets, and estate planning. It argues that there are special considerations when it comes to minors and their control over their digital assets upon death or incapacity. First are issues concerning the capacity of minors. This is important in two contexts: the capacity of minors to execute a binding estate planning instrument and to enter into a contract with a service provider. Second, it observes that internet law does not treat all minors under the age of eighteen the same. The article offers guidance on how parents, children, and estate planners might approach digital asset planning.
Neurofilament light chain: An important step toward a disease biomarker in multiple sclerosis

Multiple sclerosis (MS) is a chronic progressive disorder of the CNS that leads to neurodegeneration and accumulation of neurologic disability. At disease onset, it is challenging to predict whether individual patients will have a benign or aggressive disease course, and whether individual patients will respond to disease-modifying therapies. MS phenotypes1 and diagnostic criteria2 are defined on the basis of clinical and MRI characteristics. They are limited in their ability to guide treatment decisions.
Nucleon Spin Structure and Large $p_T$ Processes at $pp$ Colliders

QCD motivated polarized parton distributions, evolved directly in $x$-space, are used to predict rates for prompt photon production at RHIC centre of mass energies. Various scenarios for the polarized gluon distributions are considered and compared, and the possibility of using large $p_T$ processes in polarized $pp$ collision experiments to choose between them is analyzed.
Race, Gender, and Nation in an Age of Shifting Borders: The Unstable Prisms of Motherhood and Masculinity

The contributions that critical race theory scholars have made to the literature on nation, borders, and sovereignty have become even more salient in the Age of Trump. However, what remains undertheorized is how gender intersects with race in the legal construction of nation and borders today. In particular, this essay analyzes two common tropes in the current immigration debate – the “criminal” and the “welfare cheat” –not only to demonstrate how these narratives have been used to justify restrictive immigration law and policy, but also how they are used to reinforce and even shift legal constructions of nationhood and borders as both raced and gendered.