cssi/SciSciGPT-SciSciNet huggingface dataset:
A Relative Consistency Proof

Let C be an axiom system formalized within the first order functional calculus, and let C ′ be related to C as the Bernays-Godel set theory is related to the Zermelo-Fraenkel set theory. (An exact definition of C ′ will be given later.) Ilse Novak [5] and Mostowski [8] have shown that, if C is consistent, then C ′ is consistent. (The converse is obvious.) Mostowski has also proved the stronger result that any theorem of C ′ which can be formalized in C is a theorem of C . The proofs of Novak and Mostowski do not provide a direct method for obtaining a contradiction in C from a contradiction in C ′. We could, of course, obtain such a contradiction by proving the theorems of C one by one; the above result assures us that we must eventually obtain a contradiction. A similar process is necessary to obtain the proof of a theorem in C from its proof in C ′. The purpose of this paper is to give a new proof of these theorems which provides a direct method of obtaining the desired contradiction or proof. The advantage of the proof may be stated more specifically by arithmetizing the syntax of C and C ′.
Determination of ranged sets of design specifications by incorporating heterogeneous design capability information

Setting design specifications (targets) is a critical task in the early stages of a design process. Flexible targets can accommodate uncertainty and changes in design by postponing design commitments and preserving design freedom. In this work, a new and efficient method for obtaining a ranged set of design specifications that meets the overall design goal while incorporating heterogeneous design capability information is developed. Our proposed method involves two important aspects. First, a quantization algorithm based on rough set theory is used to decompose a design attribute space into subregions based on how well they meet the overall design goal. Second, a new design flexibility measure is used as a metric to select the most desired “target region” based on both the size of the region and the design capability information retrieved from potential design concepts. Our approach captures heterogeneous design capability information in the design attribute space and enhances the ability to adapt to evolving design knowledge as well as unexpected changes. The proposed method is much more efficient than conventional optimization algorithms for solving such problems. The proposed method is demonstrated by a numerical example and the design of a domestic blender.Copyright © 2006 by ASME
The Analysis of Countermovements

Previously overlooked dimensions of movements and countermovements in conflict (a “conflux”) are suggested. Propositions concerning the forms and outcomes of countermovements are delineated. Civil rights and anti-busing protest in Boston serves as a case study to illustrate the schema with examples from other “anti” movements. This analysis is based on the view that the study of movements and countermovements may usefully be conceptualized as a continuous dialectic of social change.
SEM low magnification stereoscopic technique for mapping surface contours: application to measurement of volume differences in human teeth due to polishing

SUMMARY SEM stereogrammetry with a low magnification mosaic of pictures is used to measure the elevation of many individual points. This random array of elevations is then connected into a triangular mesh, from which a contour map of elevation is drawn for the entire surface. Maps of surfaces before and after removal of material are used to determine the volume removed. The method is applicable to many circumstances of wear, erosion or deformation of surfaces. It is applied here to the erosion of human teeth due to dental polishing.
Regulation of quinolinic acid neosynthesis in mouse, rat and human brain by iron and iron chelators in vitro

Several lines of evidence indicate that excess iron may play an etiologically significant role in neurodegenerative disorders. This idea is supported, for example, by experimental studies in animals demonstrating significant neuroprotection by iron chelation. Here, we tested whether this effect might be related to a functional link between iron and the endogenous excitotoxin quinolinic acid (QUIN), a presumed pathogen in several neurological disorders. In particular, the present in vitro study was designed to examine the effects of Fe2+, a known co-factor of oxygenases, on the activity of QUIN’s immediate biosynthetic enzyme, 3-hydroxyanthranilic acid dioxygenase (3HAO), in the brain. In crude tissue homogenate, addition of Fe2+ (2–40 μM) stimulated 3HAO activity 4- to 6-fold in all three species tested (mouse, rat and human). The slope of the iron curve was steepest in rat brain where an increase from 6 to 14 μM resulted in a more than fivefold higher enzyme activity. In all species, the Fe2+-induced increase in 3HAO activity was dose-dependently attenuated by the addition of ferritin, the main iron storage protein in the brain. The effect of iron was also readily prevented by N,N′-bis(2-hydroxybenzyl) ethylenediamine-N,N′-diacetic acid (HBED), a synthetic iron chelator with neuroprotective properties in vivo. All these effects were reproduced using neostriatal tissue obtained postmortem from normal individuals and patients with end-stage Huntington’s disease. Our results suggest that QUIN levels and function in the mammalian brain might be tightly controlled by endogenous iron and proteins that regulate the bioavailability of iron.
Kosovo and the 'New Interventionism': Promise or Peril?

The U.S. and NATO justified their 1999 bombing of Yugoslavia and expulsion of Serb forces from Kosovo primarily on the grounds that their intervention was necessary to halt and reverse a humanitarian disaster, namely the Serbs widespread atrocities against and “ethnic cleansing” of the Albanian Kosovars. This article suggests and discusses some of the significant potential issues and problems raised by NATO’s Kosovo intervention – particularly for the UN and the doctrine of humanitarian intervention, but also for the laws of war, the role of international criminal courts, self-determination and ethnic conflict, and the role of the media and non-governmental organizations (NGOs).The article raises questions in each of these respects, especially as to both the legality and desirability of a proposed doctrine of so-called “New Interventionism,” which suggests that a state or group of states may appropriately engage in a “humanitarian intervention” even in the absence of UN participation, authorization or approval. While recognizing that the situation in Kosovo created a genuine moral and political dilemma in which some international action was perhaps unavoidable, the article warns against its use as a precedent. It also suggests that we must always be on our guard against attempts by governments, groups or individuals to appropriate the enormous potential appeal of human rights ideals for selfish rather than truly humanitarian ends.This article was the Edward Ball Chair lecture delivered at Florida State College of Law in September 1999. It draws in part on and develops ideas included in a series of lectures given by the author on “Rethinking Human Rights: What Have We Learned, Where Are We Going?” delivered at the European University Institute, Academy of European Law, Tenth Anniversary Session on Human Rights, in France and Italy during the summer of 1999.
Deposit Formation by Diffusion of Flame Intermediates to a Cold Surface

The problem of deposit formation on cold surfaces is important in a number of combustion systems and is of special interest in the Otto-cycle engine, where octane requirement is significantly increased above that for a clean engine by the formation of deposits on combustion chamber walls. Past work on this problem supplies information on the effects of fuel, lubricant, and engine variables on the formation of deposits. Elemental analysis and other limited information on deposit composition are also available; however, very little Information is available on the chemical species that reach the surface from the flame to cause these deposits.
Detergent inhibits 70–90% of responses to intravenous endotoxin in awake sheep

Sheep have reactive pulmonary intravascular macrophages, which are essential for the marked pulmonary vascular response to infusions of small quantities of endotoxin. In another species with reacti...
Mexican Mortgages: Structure and Default Incentives, Historical Simulation, 1982 to 1998

In 1995, the Mexican government sponsored a price-level adjusting credit system based on a unit of account called the UDI. This research examines the mechanics and behavior of UDI mortgages and compares them with dual-index mortgages (DIMs) in a simulation under the most volatile economic conditions in Mexico's recent history. We use Mexican economic data from February 1982 through January 1998 to simulate changes in payment-to-income ratios, equity-to-value ratios, and yields, both in pesos and dollars.Results indicate that UDI borrowers opting for the constant-amortization payment plan had low default incentives during most of the study period, reaching moderately high levels for a brief period of time for some borrowers. A comparison reveals that the DIMs used in Mexico resulted in greater incentives to default. We conclude that UDI mortgages are preferable to DIMs and offer greater potential for expansion of Mexico's mortgage markets.
Retinal Changes with Aging

The human fovea undergoes numerous changes during normal aging. Optical and psychophysical techniques allow us to measure these changes in vivo, using non-invasive techniques.
An Intrinsic Equation Solution of a Problem of Euler

(1917). An Intrinsic Equation Solution of a Problem of Euler. The American Mathematical Monthly: Vol. 24, No. 9, pp. 420-422.
Mitochondrial-DNA Analysis of the Systematic Relationships within the Peromyscus maniculatus Species Group

Both parsimony and distance-based phylogenetic analyses of sequence data from three mitochondrial DNA (mtDNA) genes (ND3, ND4L, and ND4) revealed that, as currently recognized, the Peromyscus maniculatus species group is polyphyletic. This apparent poly-phyly is resolved when P. slevini is removed from the species-group, thus limiting the group to P. maniculatus, P. keeni, P. polionotus, P. sejugis , and P. melanotis . Additionally, the phylogenetic analysis revealed that P. m. coolidgei is closer to P. sejugis than to the other subspecies of P. maniculatus examined. The systematic integrity of P. maniculatus is further complicated by the sister-species relationship between P. keeni and P. sejugis-P. m. coolidgei . These relationships suggest either a high degree of lineage sorting within P. maniculatus or that some of the currently recognized subspecies may be distinct species.
Metal-Organic Precursors to high Temperature Superconductors Using 2-(2-Ethoxyethoxy)Ethanol

The copper(II) alkoxide, bis(2-(2-ethoxyethoxy)ethoxide)copper(II), was prepared and had a solubility in organic solvents greatly exceeding those of simple copper(II) alkoxides (>0.4 mol/L in toluene at room temperature). Copper 2-(2-ethoxyethoxy)ethoxide (2-(2-ethoxyethoxy)ethoxide = 2,2-EEE) toluene or toluene/THF solutions gelled upon exposure to moisture. These solutions were hydrolysed with 0.2, 1.0, 2.0, 4.0, and 20.0 equivalents of H2O and the resulting powders were characterized by IR spectroscopy and SEM.
LORAKS makes better SENSE: Phase-constrained partial fourier SENSE reconstruction without phase calibration.

Purpose Parallel imaging and partial Fourier acquisition are two classical approaches for accelerated MRI. Methods that combine these approaches often rely on prior knowledge of the image phase, but the need to obtain this prior information can place practical restrictions on the data acquisition strategy. In this work, we propose and evaluate SENSE-LORAKS, which enables combined parallel imaging and partial Fourier reconstruction without requiring prior phase information. Theory and Methods The proposed formulation is based on combining the classical SENSE model for parallel imaging data with the more recent LORAKS framework for MR image reconstruction using low-rank matrix modeling. Previous LORAKS-based methods have successfully enabled calibrationless partial Fourier parallel MRI reconstruction, but have been most successful with nonuniform sampling strategies that may be hard to implement for certain applications. By combining LORAKS with SENSE, we enable highly accelerated partial Fourier MRI reconstruction for a broader range of sampling trajectories, including widely used calibrationless uniformly undersampled trajectories. Results Our empirical results with retrospectively undersampled datasets indicate that when SENSE-LORAKS reconstruction is combined with an appropriate k-space sampling trajectory, it can provide substantially better image quality at high-acceleration rates relative to existing state-of-the-art reconstruction approaches. Conclusion The SENSE-LORAKS framework provides promising new opportunities for highly accelerated MRI. Magn Reson Med 77:1021–1035, 2017. © 2016 International Society for Magnetic Resonance in Medicine
RNAi knockdown of HdmX or Hdm2 leads to new insights into p53 signaling.

3640 Cell Cycle Volume 9 Issue 18 The p53 tumor suppressor protein is a central player in the cellular response to stress and considerable evidence supports that p53 inactivation plays a critical in human tumorigenesis. While nearly half of all human tumors inactivate p53 through gene mutation or deletion, remaining tumors harbor inactive wildtype p53 protein through deregulation of various components in the p53 signaling pathway. A growing interest has developed in understanding the therapeutic implications of p53 reactivation by targeting p53 inhibitors. On the forefront of potential therapeutic targets are the p53 negative regulators Hdm2 and HdmX. Originally discovered as associating with p53, Hdm2 overexpression is seen in about 20% of human tumors, the majority harboring wild-type p53. HdmX overexpression is seen in a similar percentage of human tumors with retinoblastomas showing the highest percentage (65%) of HdmX deregulation. In the paper by Heminger et al, MCF7 breast cancer cells that harbor wild-type p53 and elevated levels of Hdm2 and HdmX were used to assess the biological and gene expression impact of knocking down Hdm2 or HdmX protein. As anticipated RNAi knockdown of either Hdm2 or HdmX triggered a p53-dependent cell cycle arrest as noted by colony formation assays and flow cytometry. This cell cycle arrest was transitory and while it resulted in increased p21 protein levels it did not trigger cellular senescence (K. Heminger, personal communication). It has been reported that nutlin 3a, an inhibitor of Mdm2:p53 interactions, can trigger a p53dependent but reversible cell cycle arrest in several tumor cell lines. RNAi knockdown of HdmX or Hdm2 leads to new insights into p53 signaling
Evaluation on Synergistic Effect of Acidizing Corrosion Inhibitor and Surfactant

Using the static coupon method,the corrosion synergistic effect of the imidazoline inhibitor and surfactant was evaluated.It was shown that when the temperature is 70℃ and the imidazoline inhibitor and surfactant was remixed,the delayed corrosion effect was better than using the imidazoline inhibitor single.The delayed corrosion effect of Q235 Steel is improved and the corrosion inhibitor can satisfy the requirement of oil field acidizing.
The major histocompatibility complex region marked by HSP70-1 and HSP70- 2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups

Genes of the major histocompatibility complex (MHC) have been associated with susceptibility to drug-induced adverse reactions. We previously found that clozapine-induced agranulocytosis (CA) is associated with the HLA-DRB1*0402, DRB4*0101, DQB1*0302, DQA1*0301 haplotype in Ashkenazi Jewish patients and with the HLA-DRB1*1601, DRB5*02, DQB1*0502, DQA1*0102 haplotype in non-Jewish patients. In the present study, we tested the hypothesis that the variants of the heat-shock protein 70 (HSP-70) encoded by the HSP-70 loci located within the MHC region and known to be involved in apoptosis and regulation of cell proliferation could play an important role in molecular mechanisms of CA. First, we analyzed HSP70-2 polymorphism in risk-associated haplotypes from HLA homozygous cells and normal individuals and confirmed that the HSP70-2 9-kb variant was associated invariably with DR4 (HLA-DRB1*0402, DQB1*0302) and DR2 (HLA-DRB1*01601, DQB1*0502, DQA1*0102 and HLA-DRB1*1501, DQB1*0602) haplotypes, which were the haplotypes found increased in Jewish and non-Jewish patients with CA, respectively. The 9.0-kb variant was also found to be associated with HLA-B44, DRB1*0401 and HLA-B44, DRB1*07 haplotypes. Second, in patients with CA (12 Ashkenazi Jewish and 20 non-Jewish patients), HSP70-1 A and HSP70-2 9.0-kb variants were associated with the MHC haplotypes found by us to be markers of susceptibility to CA. The clozapine-treated control group had an excess number of HSP70-1 C and HSP70-2 8.5-kb variants, consistent with genetic resistance to CA associated with those variants. This finding supports our hypothesis that a dominant gene within the MHC region (marked by HSP70-1 and HSP70-2), but not necessarily HLA, is associated with CA in two different ethnic groups.
Extracorporeal shock wave lithotripsy in a renal transplant patient.

AbstractWe report a case of nephrolithiasis in a transplanted kidney that was treated successfully with extracorporeal shock wave lithotripsy. The patient experienced transient partial obstruction after lithotripsy and, thus, intense monitoring of the transplant patient is necessary.
The Influences of Dietary Sugar and Related Metabolic Disorders on Cognitive Aging and Dementia

Abstract The influence of diet on health has become of major concern in recent years. Research indicates that increased sugar consumption has been related to the development of insulin resistance syndrome, type II diabetes (T2D), and cardiovascular disease (CVD). In addition to contributing to poor metabolic health, accumulating evidence suggests that the consumption of sugar-rich foods also plays a substantial role in accelerated brain and cognitive aging, including risk of dementia through similar mechanisms underlying dietary sugar-induced metabolic dysfunction. Here, research examining the specific influence of dietary sugar and related metabolic abnormalities on cognitive aging and dementia are discussed, with an emphasis on shared mechanistic pathways. Overall, evidence supports the theory that sugar consumption may be an important target in the identification of risk factors and treatment strategies for poor cognitive functioning and dementia in an increasingly aging population.
Hiding Death: Contextualizing the Dover Ban

ABSTRACTFollowing the terrorist attacks against the US in 2001, the Bush administration reaffirmed the Dover ban, the policy that prohibited press coverage of military coffins arriving at Dover Air Force Base from conflicts abroad. Conventional wisdom holds that the Bush administration enforced the ban in the hope of maintaining public support for the wars in Afghanistan and Iraq. This understanding, though, is incomplete. If the Dover ban were enforced only in response to eroding public opinion, then other coalition states would have responded likewise to this shared incentive. I argue instead that maintaining public support is only one factor among many that led the US to uphold this policy. In addition to considering the influence of factors such as perceived media bias and casualty aversion, I focus on necropolitics and the related impetus for governments to regulate the observation of death. Through this interpretation, part of the American response to the involuntary loss of sovereignty on 9/11 was ...
HLA-C Mismatch Is Associated with Inferior Outcome after Unrelated Donor Non-Myeloablative Hematopoietic Stem Cell Transplantation.

Donor-recipient disparity at HLA-C is an important determinant of clinical outcome after myeloablative unrelated donor (URD) hematopoietic stem cell transplantation, but its importance in URD non-myeloablative stem cell transplantation (NST) is less clear. Methods: We performed a retrospective analysis of 111 patients who underwent unrelated donor NST for hematologic malignancies from 2000–2004. Of these, 78 were 10/10 matched at HLA-A, B, C, DRB1, DQB1, and 33 were mismatched at one or more HLA-C antigen/allele (21 single C, 3 double C, 9 single C + other HLA locus mismatch). A majority (78%) of the mismatches at HLA-C were detectable at the antigen level. Diseases included AML (24), ALL (3), MDS (17), CML (10), CLL (23), NHL (22), and HD (12). All patients received non-myeloablative conditioning with intravenous busulfan (0.8mg/kg/d x 4 days) and fludarabine (30mg/m 2 /d x 4 days). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine plus prednisone or tacrolimus plus low-dose methotrexate based regimens. Stem cell source was primarily G-CSF mobilized PBSC. Results: Median time to neutrophil engraftment (ANC > 500/ul) among patients who nadired was 12 days (range 8–21 days) in both groups. Median unfractionated marrow donor chimerism were ≥ 90% donor at day+30 and day +100 in both groups. There was one late graft failure in the C-mismatched cohort, and one early graft rejection in the 10/10 matched cohort. HLA-C disparity was associated with an increased risk for grade III-IV acute GVHD (33% vs. 12%, p = 0.01) in univariate and multivariate logistic regression analyses (odds ratio 3.6, p = 0.03). This finding remained significant even when baseline differences in GVHD prophylaxis between the 2 cohorts were taken into consideration. Cumulative relapse incidence was not statistically different: 35% in the C-mismatched group, versus 55% in the 10/10 matched cohort, p = 0.09. There was a higher incidence of treatment related mortality in the C-mismatched group: 48% versus 16% ( p = 0.001). Overall survival at 2 years was 27% in C-mismatched, vs. 47% in 10/10 matched patients ( p = 0.009). In Cox regression model, HLA-C disparity was an independent factor for poor survival (hazard ratio 1.85, p = 0.04). Conclusions: Donor recipient disparity at HLA-C does not influence engraftment or donor chimerism after URD NST, but is associated with increased acute GVHD and inferior survival. HLA-C is an important transplantation antigen and should be considered in the selection of unrelated donors for NST.
The Early Preclinical Development Program for Locally Administered Investigational Medicinal Products in Ophthalmology: Preclinical Data Required for Starting a First-in-Human Clinical Trial in Europe-Basic Considerations and 2 Case Studies.

Background:Although regulatory guidance defines which preclinical data are required in general before proceeding to first-in-human clinical trials, a certain level of flexibility exists in the actu...
Nutrition Label Use and Sodium Intake in the U.S.

Introduction High sodium intake is a major risk factor for hypertension, but evidence is limited on which interventions are effective in reducing sodium consumption. This study examined the associations between frequent use of nutrition labels and daily sodium intake and the consumption of high-sodium foods in the U.S. Methods Using the 2007–2008 and 2009–2010 Flexible Consumer Behavior Survey, this study compared sodium intake measured from the 24-hour dietary recalls, availability of salty snacks at home, and frequencies of eating frozen meals/pizzas between frequent (i.e., always or most of the time) and infrequent nutrition label users. Also, the study examined the association between nutrition label use and sodium-related dietary behaviors across different demographic and socioeconomic groups. Data were analyzed in 2016. Results Frequent users of nutrition labels consumed 92.79 mg less sodium per day (95% CI= −160.21, −25.37), were less likely to always or most of the time have salty snacks available at home (OR=0.86, 95% CI=0.76, 0.97), but were just as likely to eat frozen meals or pizzas (incidence rate ratio=0.96, 95% CI=0.84, 1.08) compared with infrequent label users. The associations between nutrition label use and sodium intake differed considerably across age, gender, and socioeconomic groups. Conclusions Frequent use of nutrition labels appears to be associated with lower consumption of sodium and high-sodium foods in the U.S. Given this small reduction, interventions such as enhancing nutrition label use could be less effective if implemented without other strategies.
Doped dielectric polymers with low dielectric constant nanofillers

Nanoparticles, through interfacial effects, can markedly influence material properties of the matrix. Here we report the finding of a significantly enhanced dielectric response in dipolar polymers such as polytherimide (PEI) by doping with very low volume content nanoparticles. The presence of nanoparticles reduces the constraints on the dipole response to the applied electric field in the interfacial region, thus enhancing the dielectric constant. The finding eliminates the practical constraint of the traditional dielectric nanocomposites, where in order to raise the dielectric constant, inorganic particles with much higher dielectric constants are added to the polymer matrix, causing high local electric fields in the polymer and resulting in a large reduction of the electric breakdown strength. Our results demonstrate that through nanostructure engineering, the dielectric constant of polymers can be enhanced markedly without using high dielectric constant nanoparticles, thereby not compromising on breakdown strength.
From the Digital to the Physical: Federal Limitations on Regulating Online Marketplaces

Online marketplaces have transformed how we shop, travel, and interact with the world. Yet, their unique innovations also present a panoply of challenges for communities and states. Surprisingly, federal laws are chief among those challenges despite the fact that online marketplaces facilitate transactions traditionally regulated at the local level. In this Article, we survey the federal laws that frame the situation, especially §230 of the Communications Decency Act (CDA), a 1996 law largely meant to protect online platforms from defamation lawsuits. The CDA has been stretched beyond recognition to prevent all manner of prudent regulation. We offer specific suggestions to correct this misinterpretation to assure that state and local governments can appropriately respond to the digital activities which impact physical realities.
Geometric Quantization for Nilpotent Coadjoint Orbits

Suppose G is a Lie group, g its Lie algebra, and g* the dual vector space. It is a classical idea of Kirillov and Kostant (see [10] and [11]) that irreducible unitary representations of G are related to the orbits of G on g*.
The intraventricular-spot sign: prevalence, significance, and relation to hematoma expansion and outcomes

The presence of the spot sign on computed tomography angiogram (CTA) is considered a sign of active bleeding, and studies have shown it can predict hematoma expansion in intraparenchymal hemorrhage (IPH). The spot sign in intraventricular hemorrhage (IVH) has not been explored yet. The purpose of this study is to estimate the prevalence of the intraventricular-spot sign, and its prediction of hematoma expansion and clinical outcomes. We retrieved data of hemorrhagic stroke patients seen at our medical center from January 2013 to January 2018. A total of 321 subjects were filtered for the prevalence analysis (PA). We further excluded 114 subjects without a follow-up CT-head for the hematoma expansion analysis (HEA). Patients were grouped based on the location of hemorrhage into three groups: isolated IPH with the spot sign always in IPH (i-IPH), isolated IVH with the spot sign always in IVH (i-IVH), and combined IPH and IVH which would be further sub-grouped according to the location of the spot sign: in IPH only (IPH+/IVH) and in IVH only (IPH/IVH+). The prevalence, demographics, and incidence of hematoma expansion were compared between the groups using Pearson’s chi-square test and Student’s t test. The prevalence of the spot sign was 8, 20, 17, 5% in (i-IPH), (i-IVH), (IPH+/IVH), and (IPH/IVH+) groups, respectively. The rate of hematoma expansion were (42 vs. 13%), (33 vs. 31%), (80 vs. 22%), and (25 vs. 22%) in spot sign positive vs. negative subjects in each group, respectively (p values = 0.023, = 1, <0.001, and = 1). We studied the prediction of spot sign on hematoma expansion and clinical outcomes in the different subtypes of ICH. Our study showed that spot sign is a good predictor in IPH but not IVH. Despite the rarity of IVH; the prevalence of spot sign was higher in IVH than IPH. This might be due to anatomical and physiological variations.
Abstract 346: Targeting DNA repair with the combination of p97 and HDAC6 inhibitors in mantle cell lymphoma

p97 is an ATPase which is involved in remodeling multi-subunit protein complexes. It plays a pivotal role in the retrotranslocation and proteasomal degradation of misfolded ubiquitinated proteins in the endoplasmic reticulum. In association with cytosolic histone deacetylase 6 (HDAC6), p97 promotes the autophagic degradation of polyubiquitylated proteins and damaged organelles. More recently p97 has been implicated in regulating cell division and in facilitating DNA repair by promoting the recruitment of DNA repair proteins to the site of DNA damage. In this study, we determined the molecular mechanisms through which HDAC6 promotes p97 function in mantle cell lymphoma (MCL) cells. We report that treatment of MCL cells with the p97 inhibitors, DBeQ, ML240, NMS-873 and CB-5083 induces ER stress markers GRP78 and CHOP and resulted in dose-dependent apoptosis. Treatment of Z138C xenografts in NSG mice with CB-5083, the first in-class p97 inhibitor, resulted in increased accumulation of polyubiquitylated proteins and improved survival in vivo compared to control mice. Co-treatment with CB-5083 and the HDAC6-selective inhibitor ACY-1215, resulted in accumulation of polyubiquitylated proteins, impaired DNA double-stranded break repair and resulted in the partial depletion of BRCA1 and Cyclin D1 in MCL cells compared to either agent alone. We also demonstrate that shRNA-mediated knockdown of HDAC6 induced enhanced accumulation of H2AX-γ under basal conditions and following treatment with CB-5083 in cultured and primary MCL cells. Finally, treatment of MCL cells with p97 inhibitors and ACY-1215 results in synergistic apoptotic cell death in MCL cells. Collectively our studies create a strong rationale to test efficacy of the combination of p97 inhibitors in combination with HDAC6 inhibitors in MCL. Citation Format: Pratikkumar Vekaria, Anusha Vallurupalli, Dharmalingam Subramaniam, Frank Schoenen, Joseph McGuirk, Rekha M. Rao. Targeting DNA repair with the combination of p97 and HDAC6 inhibitors in mantle cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 346.
Narcissists’ Perceptions of Narcissistic Behavior

Do narcissists view their narcissistic reputations and behavior as a curse or a blessing? Herein, we reviewed studies that have addressed narcissists’ (a) awareness of their narcissistic reputation and behavior, (b) evaluations of their narcissistic traits and behavior, (c) perspective on their prototypical narcissistic action as strategic (i.e., a pattern of behavior designed to accomplish goals) vs. impulse-driven, and (d) evaluation of other narcissists. Our review suggested that narcissists are generally aware that they are more “narcissistic,” view their own prototypical narcissistic traits and behaviors as both rather beneficial and highly strategic, and are more tolerant of other people that behave narcissistically. Perhaps this constellation of findings suggests that “narcissism” possesses subjective logic and can be understood in terms of straightforward normative models of human behavior (e.g., people act “narcissistically” because they think “narcissistic” images lead to more favorable life outcomes). We conclude by discussing areas for future research in this vein.
A Survey of Digital Literacy in General Education Degree Requirements at Southern Utah University Peer Institutions

Digital literacy does not have the long-standing tradition in academics that other curriculum topics have, e.g. Mathematics. This lack of long-standing tradition surrounding computing, and the current breadth of possible digital literacies, has given rise to many varied curriculum approaches at higher education institutions. Faculty, and other curriculum creators at Southern Utah University (SUU), are currently creating digital literacy curriculum that is both integrative, and focuses on just in time learning, but these curriculum creators struggle with determining proper digital literacy requirements that should be required of all students in a General Education (GE) curriculum. This paper records the approaches towards digital literacy found at SUU, its peer institutions, and other Higher Education Institutions in the State of Utah.
“Black Genius, Asian Fail”: The Detriment of Stereotype Lift and Stereotype Threat in High-Achieving Asian and Black STEM Students:

Asians are typically situated at the top of the STEM educational and career hierarchy and enjoy a host of material benefits as a result. Thus, their STEM lives are often considered problem-free. Th...
Hardware Obfuscation Through Reconfiguration Finite Field Arithmetic Units

Intellectual property (IP) piracy and electronic counterfeiting have emerged as critical threats to the semiconductor industry in the current horizontal business model where the supply chain usually involves a large number of vendors. Hence, techniques that can protect integrated circuit (IC) against reverse engineering are demanded, especially for security-critical tasks. Hardware obfuscation is a broad category of techniques that could create ambiguity to the adversary by hiding the actual information from illegitimate users. This paper presents a novel hardware obfuscation design through reconfigurable finite field arithmetic units, which can be employed in various error correction and cryptographic algorithms. The effectiveness and efficiency of the proposed methods are verified by an obfuscated reformulated inversion-less Berlekamp-Massey (RiBM) Reed-Solomon decoder. Our experimental results show the hardware implementation of RiBM based Reed-Solomon decoder built using reconfigurable field multiplier designs. The proposed design provides only very low overhead.
TeamTalk: Interprofessional Team Development and Communication Skills Training.

Background: Communication training is a hallmark of palliative care education. The purpose of this article is to report on the development, exploratory outcomes, and lessons learned from a pilot pr...
DNA methylation biomarkers discovered in silico detect cancer in liquid biopsies from non-small cell lung cancer patients

Identification of cancer-specific methylation of DNA released by tumours can be used for non-invasive diagnostics and monitoring. We previously reported in silico identification of DNA methylation loci specifically hypermethylated in common human cancers that could be used as epigenetic biomarkers. Using DNA methylation specific qPCR we now clinically tested a group of these cancer-specific loci on cell-free DNA (cfDNA) extracted from the plasma fraction of blood samples from healthy controls and non-small cell lung cancer (NSCLC) patients. These DNA methylation biomarkers distinguish lung cancer cases from controls with high sensitivity and specificity (AUC = 0.956), and furthermore, the signal from the markers correlates with tumour size and decreases after surgical resection of lung tumours. Presented observations suggest the clinical value of these DNA methylation biomarkers for NSCLC diagnostics and monitoring. Since we successfully validated the biomarkers using independent DNA methylation data from multiple additional common carcinoma cohorts (bladder, breast, colorectal, oesophageal, head and neck, pancreatic or prostate cancer) we predict that these DNA methylation biomarkers will detect additional carcinoma types from plasma samples as well.
Vulcan: a state-aware fuzzing tool for wear OS ecosystem

This demo abstract introduces Vulcan, a fuzz testing tool for evaluating the robustness of wearable device by injecting intra-device and inter-device communication messages. Vulcan first builds a state-model of a wearable app by offline training then steers the app to a target state for injecting mutated messages. The target state of the app typically runs a high number of concurrent processes. By testing a set of 100 popular Wear OS apps, Vulcan was able to trigger 45 unique crashes and 18 system reboots. These system reboots are triggered by a fuzzing user-level app and we present a mitigation strategy to prevent it.
Ophthalmic Trauma in Basketball

Ocular injuries are common in basketball, and evidence indicates that ocular injuries may be more common in basketball than any other sport. Most of these injuries are benign and self-limiting without persistent visual impairment. However, the assessment of ocular injuries is of extreme importance and often requires an ophthalmologist’s assistance for accurate diagnosis and treatment. A wide array of diagnoses are possible, each with specific strategies for ideal management. Herein we review the epidemiology of ocular injuries, describe guidelines for sideline ocular assessment, and highlight common ocular injuries, describing each condition, its treatment, and guidelines for safe return to play.
Bank Competition and Borrower Conservatism

We study the influence of bank competition on U.S. public borrowers’ accounting conservatism by exploiting the staggered adoption of the Riegle-Neal Interstate Banking and Branching Efficiency Act (IBBEA) of 1994, which increased the threat of new bank entrants and competition. We find that borrowers’ conditional conservatism fell after IBBEA adoption, suggesting that IBBEA reduced banks’ bargaining power and their ability to demand conservatism. Conservatism fell more for firms located in states with weak incumbent banks, relying more on bank loans, and having fewer large shareholders and analysts to monitor them. We also find that loans included fewer covenants after IBBEA. Finally, we explore how firms reduce their commitment to conservatism and find that bank loan borrowers became less likely to choose Big N auditors and industry specialist auditors after IBBEA.
Temperature dependence of contact quality inducing suppression of stick–slip friction

Abstract Atomic-scale stick–slip friction of monolayer graphene on a copper substrate is computationally studied at a wide range of temperatures, which reveals strong temperature dependence of friction force and friction mode. The increase in temperature distorts regular stick–slip behavior and causes a nonlinear decrease of friction force, demonstrating a friction behavior transition from athermal friction to thermally activated. By analyzing atomic morphologies, the true contact area, defining the number of atoms interacting across the interface, shows a weak temperature dependence, yet the quality of interfacial contact substantially varies with temperature. Spatial distributions of atomic friction force uncover the significant effect of Moire superlattices, that act as strong pinning sites at low temperatures, partly change to pushing due to nonconcurrent atomic jumps at high temperatures, which leads to a chaotic friction mode with reduced lateral force. Additionally, we demonstrate the role of superlattices in strengthening friction and dictating the periodic stick–slip motion of interfacial sliding.
Alcohol use and perceived drinking risk trajectories across adolescence: the role of alcohol expectancies

The current longitudinal study tested pathways between alcohol expectancies at baseline and both perceived drinking risk and alcohol use trajectories over a five-year period through adolescence. An adolescent community sample (N = 243; Wave 1 demographics: 45% female, 51% non-white, 49% white, mean age = 13.06 years) completed self-report questionnaires annually for five years. Measures included the Alcohol Expectancy Questionnaire – Adolescent Brief Version, one Youth Risk Behavior Survey (YRBS) item assessing annual perceived drinking risk, an adapted item from the YRBS assessing annual alcohol use, the Revised Children’s Anxiety and Depression Scale, and the Disruptive Behavior Disorders Rating Scale. We specified dual latent growth curves to estimate trajectories of change in perceived drinking risk and alcohol use over time. Alcohol use significantly increased, while perceived drinking risk significantly decreased. More positive alcohol expectancies at baseline predicted a less steep decline in perceived drinking risk (β = 0.31, p = .009), whereas more negative expectancies at baseline predicted a steeper decline in perceived risk (β = −0.26, p = .03). Alcohol expectancies did not directly predict alcohol use, but instead operated indirectly via the starting point of the perceived drinking risk trajectory. Specifically, greater positive expectancies (B = -0.19, p < .001) and lower negative expectancies (B = 0.17, p = 0.006) predicted a lower risk perception trajectory starting point, which then predicted a greater alcohol use trajectory starting point (B = -1.41, p < .001). Findings underscore the starting point of perceived drinking risk trajectories as one factor linking alcohol expectancies and alcohol use. Prevention efforts aimed at shifting these starting points and altering early cognitive factors may be appropriate targets for minimizing alcohol use risk.
SPAC Attack: An Examination of SPAC Director Compensation and Its Legal Implications

Special Purpose Acquisition Company (“SPAC”) directors are compensated with economic ownership of founders shares, shares which have value if the SPAC combines with an operating business and which expire worthless if that does not occur. By analyzing the public filings of the 248 SPACs that IPOed in 2020, I create a dataset of SPAC director compensation, which is the first of its kind. I find that a director of the median SPAC receives approximately 30,000 founders shares (estimated value $300,000) and a director of the average SPAC receives approximately 40,000 founders shares (estimated value $400,000). I then demonstrate how the current director compensation subjects SPACs and their directors to greater litigation risk under Delaware law. Specifically, SPAC directors may not be considered independent under Delaware law because of the structure and quantum of compensation via founders shares. Furthermore, under Delaware law, if SPAC directors are not independent, legal claims surrounding the SPAC merger may be examined under the exacting entire fairness standard rather than the deferential business judgement rule because potential procedural safeguards of the SPAC, such as the shareholder vote, may not be sufficiently “cleansing.” Finally, I propose changes in SPAC director compensation to improve director independence.
Lipid Hydroperoxide Induced Oxidation of Cysteine in Peptides

Proteins may be exposed to a variety of oxidizing conditions during food processing and storage. Examples of deliberate oxidation are the addition of bromate, acetone peroxide or benzoyl peroxide to improve dough strength in the baking industry and the direct addition of hydrogen peroxide for bleaching or preservation elsewhere in the food industry (1). However, the most common oxidizing agents are lipid hydroperoxides. Urbanization of society has necessitated increased processing, shipping and storage of food products, all of which increase the likelihood of lipid hydroperoxide formation and possible development of off-flavors and odors. In protein foods containing polyunsaturated lipids, there is the additional risk of lipid hydroperoxide-induced oxidation of proteins and, more specifically, the sulfur amino acids of proteins. The oxidative changes in amino acids have been previously reviewed extensively (2,3,4,5,6). Significant nutritional losses have been reported in proteins which have been exposed to either hydrogen peroxide or oxidizing lipids (7,8).
Transfer Pricing of Intangible Assets, E-Commerce, and International Taxation

This paper investigates the effect of e-commerce and international taxation on transfer pricing of intangible assets. In the 21st century, the fast development of e-commerce era and service companies' paradigms in proportion to the bricks-and mortar business activities pushes most tax authorities to continue the attack of transfer pricing practices of multinational companies (MNCs) by issuing new or modified transfer pricing regulations to meet these challenges. First, general understanding of the nature of intangible assets and the new trends in transfer pricing are discussed. Second, MNCs' strategies of ownership are analyzed. Third, the appropriate transfer pricing methods are investigated. Finally, it is suggested that in designing an effective transfer pricing system, MNCs should consider tax and non-tax strategies to manage global earnings; the driving motivation behind the system; the environmental conditions; incorporate short-run active features within the system; potential income tax consequences; the selection of the best transfer pricing method; and practical solutions to avoid tax audits.
Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: robust response of alveolar type 1 epithelial cells

Engineered nanoparticles (NP) are being developed for inhaled drug delivery. This route is non-invasive and the major target; alveolar epithelium provides a large surface area for drug administration and absorption, without first pass metabolism. Understanding the interaction between NPs and target cells is crucial for safe and effective NP-based drug delivery. We explored the differential effect of neutral, cationic and anionic polystyrene latex NPs on the target cells of the human alveolus, using primary human alveolar macrophages (MAC) and primary human alveolar type 2 (AT2) epithelial cells and a unique human alveolar epithelial type I-like cell (TT1). We hypothesized that the bioreactivity of the NPs would relate to their surface chemistry, charge and size as well as the functional role of their interacting cells in vivo. Amine- (ANP) and carboxyl- surface modified (CNP) and unmodified (UNP) polystyrene NPs, 50 and 100 nm in diameter, were studied. Cells were exposed to 1–100 μg/ml (1.25-125 μg/cm2; 0 μg/ml control) NP for 4 and 24 h at 37 °C with or without the antioxidant, N-acetyl cysteine (NAC). Cells were assessed for cell viability, reactive oxygen species (ROS), oxidised glutathione (GSSG/GSH ratio), mitochondrial integrity, cell morphology and particle uptake (using electron microscopy and laser scanning confocal microscopy). ANP-induced cell death occurred in all cell types, inducing increased oxidative stress, mitochondrial disruption and release of cytochrome C, indicating apoptotic cell death. UNP and CNP exhibited little cytotoxicity or mitochondrial damage, although they induced ROS in AT2 and MACs. Addition of NAC reduced epithelial cell ROS, but not MAC ROS, for up to 4 h. TT1 and MAC cells internalised all NP formats, whereas only a small fraction of AT2 cells internalized ANP (not UNP or CNP). TT1 cells were the most resistant to the effects of UNP and CNP. ANP induced marked oxidative damage and cell death via apoptosis in all cell types, while UNP and CNP exhibited low cytotoxicity via oxidative stress. MAC and TT1 cell models show strong particle-internalization compared to the AT2 cell model, reflecting their cell function in vivo. The 50 nm NPs induced a higher bioreactivity in epithelial cells, whereas the 100 nm NPs show a stronger effect on phagocytic cells.