cssi/SciSciGPT-SciSciNet huggingface dataset:
The effect of epigenetic silencing and TP53 mutation on the expression of DLL4 in human cancer stem disorder

// Zhixing Yao 1 and Zaki A. Sherif 1 1 Department of Biochemistry & Molecular Biology, College of Medicine, Howard University, Washington DC, USA Correspondence to: Zaki A. Sherif, email: // Keywords : p53, DLL4, Notch, epigenetics, angiogenesis Received : July 22, 2016 Accepted : August 02, 2016 Published : August 16, 2016 Abstract The Li-Fraumeni Syndrome (LFS), a genetically rare heterogeneous cancer syndrome, is characterized primarily by a germline p53 ( TP53 ) gene mutation. We recently discovered a balanced reciprocal chromosomal translocation t(11;15)(q23;q15) in the non-cancerous skin fibroblasts of a bilateral breast cancer patient in LFS family. This prompted us to investigate the breakpoint region of the translocation, which uncovered a gene that encodes a Notch ligand, DLL4 , (locus at 15q15.1), a key target in tumor vasculature. We analyzed DLL4 gene expression and protein level in LFS non-cancerous skin fibroblast cell lines and non-LFS cancer cell lines. DLL4 is abrogated in all the LFS cells and drastically down-regulated in breast (MCF7) and brain (IMR32) cancer cells and tumor tissue samples. However, DNA methylation studies revealed that DLL4 promoter is silenced only in MCF7 but not in LFS cells. We further investigated the regulation of DLL4 gene expression by ChIP assays, which demonstrated that p53 binds to DLL4 promoter through its association with CTCF, a chromosomal networking protein CCCTC binding factor. This implies a possible karyotype-phenotype correlation with respect to DLL4 in LFS and breast cancer initiation and progression. The drastic reduction or absence in the expression of DLL4 in LFS as well as breast and brain cancer cells is significant and supports the concept that this ligand may also play a role in cancer immune-surveillance; and its resuscitation in the tumor microenvironment may stimulate T-cell immunity and suppress tumor growth. Therefore, DLL4 may provide a strong platform as an immuno-therapeutic target in LFS and cancer patients.
The rare earths—LXXXV: Syntheses and properties of isocyanato complexes of the tripositive ions

Abstract Crystalline lanthanide isocyanato complexes of general formula [(C2H5)4N]3[Ln(NCO)6], where Ln = Sc, Y, Eu, Gd, Dy, Ho, Er and Yb, have been isolated from absolute ethanol solutions. Comparable complexes of the lighter lanthanide(III) ions (La3+-Sm3+) could not be isolated because of decomposition. The isolated compounds were characterized by i.r. spectroscopy and elemental analysis. I.r. data indicated that all ligand groups are nitrogen-bonded to the Ln3+ ions. Coordination number six is indicated for the Ln3+ ions.
Simultaneous Optical and Electrical Recordings

Development of antiarrhythmic electrical therapies requires knowledge of the characteristics of cardiac arrhythmias and effects of electrical stimulation on the heart. Much of the available knowledge is obtained from measurements of extracellular potentials or transmembrane potentials in the heart using electrical or optical methods. With an extracellular electrode in contact with the heart, activation of the cells is detected by observing the intrinsic negative deflection of the extracellular potential. (In this chapter, the occurrence of a rapid increase in inwardly directed membrane current during the phase zero depolarization is termed activation, whereas the transition of a dye molecule to the excited state by light absorption is termed excitation.) Maps constructed from the times of these deflections at several locations in the heart indicate the spatiotemporal distributions of activation. Also maps of the distribution of extracellular potentials in the heart during a shock reveal characteristics of the electric field, which can be correlated with effects of shocks on the activation. Extracellular potential measurements can also indicate repolarization using t-wave analysis, and action potential contour using the monophasic action potential produced by pressure or suction near the electrode. Most electrical measurements do not detect activation during a shock pulse because of interference by the shock’s electric field. Another way to examine arrhythmic activation and effects of shocks is by optical action potential measurements. An isolated heart or heart tissue specimen is stained with a transmembrane voltage-dependent fluorescent dye and illuminated with excitation light. Absorption of light by dye molecules induces an excited molecular state. The molecules emit fluorescence photons as part of the process of decay to the ground state. The
Diabetes and Fetal Malformations

Diabetic and healthy control pregnant women were followed in a multicenter collaborative study coordinated by the Epidemiological Branch, National Institute of Child Health and Human Development, Bethesda, MD.
Reflective optical limiter based on gallium arsenide

We show that a photonic structure composed of silicon dioxide, silicon nitride, and gallium arsenide layers can act as a reflective optical limiter at near-infrared wavelengths. The limiter transmits low intensity light while totally reflecting high intensity laser radiation, thereby protecting the limiter and the sensor from overheating and destruction.
Does cortical bone thickness in the last sacral vertebra differ among tail types in primates

Objectives The external morphology of the sacrum is demonstrably informative regarding tail type (i.e., tail presence/absence, length, and prehensility) in living and extinct primates. However, little research has focused on the relationship between tail type and internal sacral morphology, a potentially important source of functional information when fossil sacra are incomplete. Here, we determine if cortical bone cross-sectional thickness of the last sacral vertebral body differs among tail types in extant primates and can be used to reconstruct tail types in extinct primates. Materials and methods Cortical bone cross-sectional thickness in the last sacral vertebral body was measured from high-resolution CT scans belonging to 20 extant primate species (N = 72) assigned to tail type categories ("tailless," "nonprehensile short-tailed," "nonprehensile long-tailed," and "prehensile-tailed"). The extant dataset was then used to reconstruct the tail types for four extinct primate species. Results Tailless primates had significantly thinner cortical bone than tail-bearing primates. Nonprehensile short-tailed primates had significantly thinner cortical bone than nonprehensile long-tailed primates. Cortical bone cross-sectional thickness did not distinguish between prehensile-tailed and nonprehensile long-tailed taxa. Results are strongly influenced by phylogeny. Corroborating previous studies, Epipliopithecus vindobonensis was reconstructed as tailless, Archaeolemur edwardsi as long-tailed, Megaladapis grandidieri as nonprehensile short-tailed, and Palaeopropithecus kelyus as nonprehensile short-tailed or tailless. Conclusions Results indicate that, in the context of phylogenetic clade, measures of cortical bone cross-sectional thickness can be used to allocate extinct primate species to tail type categories.
Multi-focal HIFU reduces cavitation in mild-hyperthermia.

Mild-hyperthermia therapy (40–45 °C) with high-intensity focused ultrasound (HIFU) is a technique being considered in a number of different treatments such as thermally activated drug delivery, immune-stimulation, and as a chemotherapy adjuvant. Mechanical damage and loss of cell viability associated with HIFU-induced acoustic cavitation may pose a risk during these treatments or may hinder their success. Here we present a method that achieves mild heating and reduces cavitation by using a multi-focused HIFU beam. We quantify cavitation level and temperature rise in multi-focal sonications and compare it to single-focus sonications at the transducer geometric focus. Continuous wave sonications were performed with the Sonalleve V2 transducer in gel phantoms and pork at 5, 10, 20, 40, 60, 80 acoustic watts for 30 s. Cavitation activity was measured with two ultrasound (US) imaging probes, both by computing the raw channel variance and using passive acoustic mapping (PAM). Temperature rise was measured with MR thermometry at 3 T. Cavitation and heating were compared for single- and multi-focal sonication geometries. Multi-focal sonications used four points equally spaced on a ring of either 4 mm or 8 mm diameter. Single-focus sonications were not steered. Multi-focal sonication generated distinct foci that were visible in MRI thermal maps in both phantoms and pork, and visible in PAM images in phantoms only. Cavitation activity (measured by channel variance) and mean PAM image value were highly correlated (r > 0.9). In phantoms, cavitation exponentially decreased over the 30-second sonication, consistent with depletion of cavitation nuclei. In pork, sporadic spikes signaling cavitation were observed with single focusing only. In both materials, the widest beam reduced average and peak cavitation level by a factor of two or more at each power tested when compared to a single focus. The widest beam reduced peak temperature by at least 10 °C at powers above 5 W, and created heating that was more spatially diffuse than single focus, resulting in more voxels in the mild heating (3–8 °C) range. Multi-focal HIFU can be used to achieve mild temperature elevation and reduce cavitation activity.
Model predictive control of large scale processes

Abstract Model predictive control is a receding horizon control policy in which a linear or quadratic program with linear constraints is solved on-line at each sampling instance. An algorithm is developed that allows quick computation of sub-optimal control moves. The linear constraint set is approximated by an ellipsoid and a change of variables is performed so that a solution may be computed efficiently via bisection. The ellipsoid is rescaled on-line to reduce conservatism. This allows the implementation of model predictive control algorithms to large scale processes using simple control hardware.
A Critique of Substance Causation

In her recent paper, “A Defense of Substance Causation,” Ann Whittle makes a case for substance causation. In this paper, assuming that causation is a generative or productive relation, I argue that Whittle’s argument is not successful. While substances are causally relevant in causal processes owing to outcomes being counterfactually dependent upon their role in such occurrences, the real productive work in causal processes is accomplished by the causal powers of substances.
The Industrialization of Services

The industrialization of services, just as with goods production and manufacturing, is a complex topic. Perhaps more so, since services are very heterogeneous, and often have features that do not exist in most manufacturing processes. A fundamental aspect of services is the lack of a tangible output; in fact in many cases the outputs and outcomes may not even be observable. That creates basic issues around the entire question of productivity at least in the sense of measurement and quantification. Another service characteristic is the presence and participation of the customer in front office service processes. This creates challenges for managing process efficiency, as well as necessitating close attention to the implications for customer experience. So one has to look at “industrialization” of services with more than a single perspective and to understand the differences between back room and front office processes.
Insurance Coverage and Health Outcomes in Young Adults With Mental Illness Following the Affordable Care Act Dependent Coverage Expansion.

OBJECTIVE As a provision of the Affordable Care Act, young adults were able to remain on their parents' health insurance plans until age 26. We examined the impact of the 2010 dependent coverage expansion on insurance coverage and health outcomes among young adults with mental illness. METHODS Data are from the 2008-2013 National Survey on Drug Use and Health, an annual population-based survey of noninstitutionalized US individuals aged 12 and older. We used a difference-in-differences approach to compare young adults with mental illness subject to the provision (aged 19-25 years, n = 19,051) with an older comparison group (aged 26-34 years, n = 7,958) before (2008-2009) and after (2011-2013) the dependent coverage expansion in their insurance coverage, use of health services, and self-reported health. RESULTS In adjusted analyses, following the dependent coverage expansion, private insurance coverage increased by 11.7 percentage points (95% CI, 8.4-15.1, P < .001) and uninsurance decreased by 8.9 percentage points (95% CI, -12.1 to -5.7, P < .001) among 19- to 25-year-olds with mental illness, relative to 26- to 34-year-olds. The provision was associated with a modest increase in young adults with mental illness who received outpatient mental health treatment at least monthly on average (+2.0% [95% CI, 0.1% to 4.0%, P = .04]) and a modest decrease in those reporting their overall health as fair or poor (-2.3% [95% CI, -4.6% to -0.0%, P = .05]). Unmet mental health needs due to cost decreased significantly among those with moderate-to-serious mental illness (-12.3% [95% CI, -22.7% to -2.0%, P = .02]), but did not change among those with mild illness. CONCLUSIONS The 2010 dependent coverage expansion was associated with an increase in insurance coverage, several indicators of mental health treatment, and improved self-reported health among young adults with mental illness.
Toward high-value gas sensing in wearable and distrubuted formats: Discrimination of complex patterns of volatiles using multi-response RFID sensors

Wearable and distributed sensors are attractive for monitoring of gases for environmental surveillance, industrial safety, and other applications. For these sensors to be of high value, they need suitable detection accuracy in complex backgrounds. Here, we show accurate detection of volatiles using low-cost sensors based on a radio-frequency identification (RFID) platform. Our design and excitation conditions of RFID sensors provide several outputs that result in three- and four-dimensional sensor response after multivariate spectral analysis. This high dimensionality of sensor response, achieved in measurements of multiple model vapors and complex patterns of volatiles, make these RFID sensors an attractive addition to high-end existing analytical instruments.
Comparison of chain-growth polymerization in solution versus on surface using reactive coarse-grained simulations

Abstract We developed a reactive coarse-grained model for chain-growth polymerization to study the chain length distribution of polymers grafted from a surface as compared to those grown in solution. The surface-initiated polymer chains exhibit a markedly broader distribution of chain lengths (larger dispersity) and slower chain growth kinetics as compared to the solution phase process. Two key factors that cause deviation from ideal grafting are identified: (1) the formation of chain “loops” with both termini attached to the substrate via recombination and (2) the “starvation” effect, in which the live chain ends of short polymers are sterically shielded from monomers by the presence of longer neighboring chains. Both effects are markedly amplified with increasing initiator surface density, thus limiting the density of high molecular weight chains grafted from the surface. Whereas the “loop” effect is absent in systems that are very strictly “living” (no termination), the starvation effect is likely operative in most real systems. Taken together, these results suggest a theoretical limit on the density of polymer brushes that can form on surfaces by a “grafting-from” technique, based on the kinetics of the chain-growth polymerization process.
Getting to “Exempt!”: Putting the Rubber Stamp on Section 501(c)(3)’s Political Activity Prohibition

Under Internal Revenue Code section 501(c)(3), certain public charities are exempt from income taxation. As a condition to this benefit, such organizations are prohibited from participating or intervening in any political campaign on behalf of, or in opposition to, a candidate for public office. The statute and the regulations promulgated thereunder, however, do not clearly define what activities are prohibited. This lack of clarity, combined with the U.S. Supreme Court’s protection of the political speech rights of other business organizations, has led many commentators to question section 501(c)(3) on constitutional grounds. Others have criticized the statutory scheme for creating inefficiencies in enforcement and compliance efforts. This Note examines the constitutional and policy questions surrounding section 501(c)(3), catalogues existing proposals to change it, and proposes its own changes to cure those deficiencies. It concludes that a bright-line rule should be used to determine when revocation of tax-exempt status is appropriate, and that revoked entities should be permitted to file for exemption under section 501(c)(4).
Wernicke’s Encephalopathy After Hyperemesis Gravidarum (P2.138)

Objective: NA Background: Wernicke’s encephalopathy is seen in patients with prolonged nutritional deprivation. Although it has been described in patients with chronic alcohol abuse, a host of other etiologies, including intractable emesis, gastrointestinal surgeries, chemotherapy, and restrictive diets, have been documented in the literature. The classically described clinical triad of Wernicke’s encephalopathy includes mental status changes, ophthalmoplegia, and gait ataxia. However, the majority of patients with Wernicke’s encephalopathy do not demonstrate all three features of this triad. Here, we describe a case of a patient who developed Wernicke’s encephalopathy secondary to hyperemesis gravidarum and presented with nystagmus in the absence of ophthalmoplegia. Design/Methods: NA Results: A 28-year-old woman presented to the emergency department with vertigo, confusion, and falls. Two weeks previously, she had a surgical abortion at 11 weeks gestation. Her pregnancy had been complicated by persistent hyperemesis gravidarum. Examination revealed impaired memory, spontaneous upbeat nystagmus, gaze-evoked nystagmus, and gait ataxia without ophthalmoplegia. MRI revealed T2 hyperintensities involving the periaqueductal white matter and bilateral thalami typical of Wernicke’s encephalopathy. The patient received high-dose intravenous thiamine with alleviation of her eye-movement abnormalities and ataxia. Conclusions: Although the classic clinical description of Wernicke’s encephalopathy includes ophthalmoplegia, some patients develop nystagmus and vestibulo-ocular reflex abnormalities in the absence of ophthalmoplegia. Gaze-evoked nystagmus is a common finding in Wernicke’s encephalopathy and may be the only initial eye movement abnormality. In patients who have not yet developed encephalopathy, thiamine administration may lead to rapid improvement in nystagmus and other eye-movement abnormalities and may prevent encephalopathy. In patients with a history of nutritional deprivation who present with spontaneous vertical and gaze-evoked nystagmus, Wernicke’s encephalopathy should be considered. Study Supported by: NA Disclosure: Dr. Anand has nothing to disclose. Dr. Gold has nothing to disclose.
The structure of sea urchin spines, large biogenic single crystals of calcite

Sea urchin spines are porous, single crystal Mg-rich calcite [(Mg, Ca)(CO3)] with a three dimensional meshwork architecture. The crystallographic orientation of large (∼10 cm in length) spines from Heterocentrotus trigonarius was determined using the X-ray back-reflection Laue technique; the long axis of all spines is parallel to the 〈00·1〉 direction of calcite. The internal structure was studied using SEM and TEM. The macropore structure dominated the SEM images, whereas many small (∼80 nm) protein occlusions can be observed within the single crystal spines using TEM. The spines appeared crystallographically perfect in the TEM. The bend strengths of a group of spines were also determined and varied between ∼13 and 41 MPa.
A na ve de-lambing method for speaker identification.

This paper addresses the issue of close-set text-independent speaker identification from speech samples recorded over telephone. We have known that the speaker identification performance variability can be attributed to many factors. One major factor is the inherent differences in the recognizability of different speakers. In speaker recognition systems such differences are characterized by the use of animal names for different types of speakers. In this paper we use lambs to refer to those speakers who are particularly easy to imitate in our closeset text-independent speaker identification system. That is, other speakers are much more likely to be recognized as these lamb speakers when they cannot be correctly recognized. Lambs adversely affect our close-set text-independent speaker identification performance a lot. In this paper we describe a naive de-lambing method to deal with these lamb speakers so as to improve our system performance. The speech data of our close-set speaker identification system is from the NIST 1999 Speaker Recognition Evaluation. Our experiments were conducted on 230 male speakers. We tried both testing from same telephone channels and sessions with training and different telephone channels and sessions with training for each speaker. Combined, the method developed in this paper result in a 15% relative improvement on the close-set 45-second training 10-second testing condition.
The Overall Research Design and Some Methodical Considerations

In the following pages we will briefly describe the design and methodology of the study. This description will include an outline of the procedures used to include minority and Anglo schoolchildren in the sample, a consideration of the major experimental comparisons that are feasible within the limits of the design, and a discussion of some design problems.
The Development of Hodgkin’s Disease and Lymphoma during Anticonvulsant Therapy

1. Six patients in whom Hodgkin’s disease or lymphosarcoma developed during the use of anticonvulsant agents (Dilantin, phenobarbital, Mysoline, Celontin) are reported. 2. The differential diagnosis from pseudolymphoma, the course of these malignant lymphomas, and their therapeutic management are discussed. 3. Based upon information presently available, it could not be determined whether the atypical hyperplasia sometimes observed during anticonvulsant drug therapy is precancerous, or whether these agents may be carcinogenic in certain sensitive individuals. 4. Patients with a seizure disorder who develop lymphoma require standard therapy for both conditions. The anticonvulsant drugs had no evident adverse effect on the course of the lymphoma, although substitution of another agent seems warranted, if possible, for the offending drug.
Chromatin rewiring mediates programmed evolvability via aneuploidy

Eukaryotes have evolved elaborate mechanisms to ensure that chromosomes segregate with high fidelity during mitosis and meiosis, and yet specific aneuploidies can be adaptive during environmental stress. Here, we identify a chromatin-based system for inducible aneuploidy in a human pathogen. Candida albicans utilizes chromosome missegregation to acquire resistance to antifungal drugs and for ploidy reduction after mating. We discovered that the ancestor of C. albicans and two related pathogens evolved a variant of histone H2A that lacks the conserved phosphorylation site for Bub1 kinase, a key regulator of chromosome segregation. Expression of this variant controls the rates of aneuploidy and antibiotic resistance in this species. Moreover, CENP-A/Cse4, the histone H3 that specifies centromeres, is depleted from tetraploid mating products and virtually eliminated from cells exposed to aneuploidy-promoting cues. Thus, changes in chromatin regulation can confer the capacity for rapid evolution in eukaryotes.
Retrospectives: On the Genius Behind David Ricardo's 1817 Formulation of Comparative Advantage

Last year marked the 200th anniversary of Ricardo's famous "four numbers" paragraph on comparative advantage, which is one of the oldest analytical results in economics. Following the lead of James Mill (1821), these four numbers have been interpreted as unit labor coefficients. This interpretation has provided the basis for the development of the 'Ricardian model' from John Stuart Mill (1852) to Eaton and Kortum (2002). However, if we accept the labor unit interpretation of these numbers, Ricardo's exposition in his 1817 Principles of Political Economy and Taxation makes little logical sense. Building on Sraffa's (1930) interpretation of Ricardo's numbers as labor embodied in trade, our discussion reveals the amazing simplicity and generality of Ricardo's comparative advantage formulation and gains-from-trade logic.
Thermoelectric Properties of NaCo 2-x Fe x O y

NaCo2O4 has one of the highest figures of merit among all ceramic thermoelectric materials. Because of its large thermopower and low resistivity, the ceramic oxide NaCo2O4 is a promising candidate for potential thermoelectric applications. NaCo2O4 is, moreover, a ceramic compound with high decomposition temperature and chemical stability in air and it does not contain any toxic elements. Like all 3-d transition ions, Co ions have multiple spin and oxidation states. In this investigation, thermopower and electrical conductivity of NaCo2O4 as a function of substitution of Co by Fe ions were measured. Fe substitution for Co causes resistivity to increase, whereas the Seebeck coefficient remained nearly invariant, especially above 330 K.
Cross Reality Spaces in Engineering Education – Online Laboratories for Supporting International Student Collaboration in Merging Realities

This paper discusses online laboratories as cross reality spaces in education. Cross Reality (also XR) as a term is borrowed from the field of gaming and broadly describes the integration of immersive, augmented, mixed, and virtual reality technology within physical reality. Online laboratories form an ideal example, as different realities (the real hands-on world in real labs, the virtual world in simulated labs or even a mixture of both in context with remote labs) are merged. The connection between different realities in laboratory education and their relation to engineering education contexts are discussed by describing a three-dimensional matrix for categorizing (online) laboratories in teaching and displaying current research results in this area. On basis of this, a scholarly research study is discussed, which is making use of a remote lab in mechanical engineering education for an international student body. In this study, the lab and its application are evaluated from the learner, the system, and the course perspective. These three perspectives offer a holistic view of the lab and the students’ learning. The study proofs a positive effect on the students learning experiences. The results also show which current needs and future potentials lie on the intersection of engineering education, internationalization, and digitalization in terms of collaborating and learning in Cross Reality Spaces.
A novel antibody-cell conjugation method to enhance and characterize cytokine-induced killer cells

Abstract Background Cytokine-induced killer (CIK) cells are an ex vivo–expanded cellular therapy product with potent anti-tumor activity in a subset of patients with solid and hematologic malignancies. We hypothesize that directing CIK cells to a specific tumor antigen will enhance CIK cell anti-tumor cytotoxicity. Methods We present a newly developed method for affixing antibodies directly to cell surface proteins. First, we evaluated the anti-tumor potential of CIK cells after affixing tumor-antigen targeting monoclonal antibodies. Second, we evaluated whether this antibody-conjugation method can profile the surface proteome of CIK cells. Results We demonstrated that affixing rituximab or daratumumab to CIK cells enhances cytotoxic killing of multiple lymphoma cell lines in vitro. These ‘armed’ CIK cells exhibited enhanced intracellular signaling after engaging tumor targets. Cell surface proteome profiling suggested mechanisms by which antibody-armed CIK cells concurrently activated multiple surface proteins, leading to enhanced cytolytic activity. Our surface proteome analysis indicated that CIK cells display enhanced protein signatures indicative of immune responses, cellular activation and leukocyte migration. Conclusions Here, we characterize the cell surface proteome of CIK cells using a novel methodology that can be rapidly applied to other cell types. Our study also demonstrates that without genetic modification CIK cells can be rapidly armed with monoclonal antibodies, which endows them with high specificity to kill tumor targets.
Effect of BMI on clinical outcomes following minimally invasive sacrocolpopexy.

Our objective was to compare success and complication rates following minimally invasive sacrocolpopexy (SCP) based on body mass index (BMI). This is a retrospective cohort study of women who underwent laparoscopic or robotic SCP at one academic center from 2006 to 2016. Women were included if they had a postoperative pelvic organ prolapse quantification (POPQ) exam and subjective success documented. For our primary outcome, we compared composite success (POPQ stage ≤ I and report of no bulge symptoms) amongst three groups: normal weight (BMI ≤ 25), overweight (BMI 25–30) and obese (BMI ≥ 30) women. Secondary outcomes included intraoperative complications, 6 week postoperative complications, and sacrocolpopexy mesh exposure. Of the 431 women who met inclusion criteria, 140 (32%) had normal BMI (23 kg/m2; IQR 22, 24), 177 (41%) were overweight (27 kg/m2; IQR 26, 28), and 114 (26%) were obese (32 kg/m2; IQR 31, 36). Mean age was 60 ± 11 years, and most were Caucasian, with no differences in demographics or Charlson Comorbidity Index (CCI). Median length of follow-up was 49 weeks (IQR 9, 104), with similar follow-up for all groups. For our primary outcome, composite success was 72% overall, with no significant differences in composite success rates between groups. For secondary outcomes, there were no differences in the rates of perioperative complications but obese women had a 2.8 increased risk of mesh exposure (p = 0.02). Obesity was not associated with differences in the success or peri-operative complication rates for SCP in our population, but was associated with mesh exposure.
Tatonnement modeling with linear programming: demand and supply for some United States crops in 2000

During the last decade, two concerns have been raised about the future of U.S. crop production. These concerns are: (a) Will the United States have enough land available in the future that is suitable for crop production? and (b) What will future crop yields be? Future U.S. crop production is highly dependent upon both these issues;The real problem may not be the quantity of future crop production, but rather the price of the quantity that is available. The development of a model to answer this question is one of the objectives of this study. The other objective is the projection of prices and quantities for barley, corn, oats, sorghum, soybeans, and wheat for the year 2000 under alternative yield and land availability assumptions;An iterative model based on the theory of tatonnement process of market adjustments is developed using a linear programming model to stimulate the behavior of producers and demand equations estimated econometrically to stimulate the behavior of consumers. The iterative model starts at an arbitrary level of demand for each commodity and solves for approximate equilibrium prices and quantities;The iterative model is used to estimate approximate equilibrium prices and quantities for barley, corn, oats, sorghum, soybeans, and wheat and supply prices for corn silage, sorghum silage, legume hay, other hay, and cotton for the year 2000. Seven scenarios consisting of three alternative yield levels and three alternative levels of land constraints are run and analyzed;The results from the seven scenarios suggest that the future equilibrium prices and quantities are highly dependent upon the assumptions made about future crop yields and future cropland availability. The highest equilibrium price for barley, corn, oats, sorghum, wheat, and soybeans is 182.1, 158.8, 145.3, 165.1, 182.4, and 208.9 percent higher than the lowest equilibrium price, respectively.
Production and comprehension of pronouns in individuals with autism: A meta-analysis and systematic review

This study compared pronoun use in individuals with autism to their typically developing peers via meta-analysis and systematic review of 20 selected articles to examine differences in overall pron...
Is Melatonin the Cornucopia of the 21st Century

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes and extra-pineal cells, plays an important role in timing circadian rhythms (24-h internal clock) and regulating the sleep/wake cycle in humans. However, in recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant and free radical scavenging action. Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. Melatonin-induced signal transduction through melatonin receptors promotes the expression of antioxidant enzymes as well as inflammation-related genes. Melatonin also exerts an immunomodulatory action through the stimulation of high-affinity receptors expressed in immunocompetent cells. Here, we reviewed the efficacy, safety and side effects of melatonin supplementation in treating oxidative stress- and/or inflammation-related disorders, such as obesity, cardiovascular diseases, immune disorders, infectious diseases, cancer, neurodegenerative diseases, as well as osteoporosis and infertility.
Validation of SATURN, a free, electronic, self-administered cognitive screening test

Background Cognitive screening is limited by clinician time and variability in administration and scoring. We therefore developed Self-Administered Tasks Uncovering Risk of Neurodegeneration (SATURN), a free, public-domain, self-administered, and automatically scored cognitive screening test, and validated it on inexpensive (<$100) computer tablets. Methods SATURN is a 30-point test including orientation, word recall, and math items adapted from the Saint Louis University Mental Status test, modified versions of the Stroop and Trails tasks, and other assessments of visuospatial function and memory. English-speaking neurology clinic patients and their partners 50 to 89 years of age were given SATURN, the Montreal Cognitive Assessment (MoCA), and a brief survey about test preferences. For patients recruited from dementia clinics (n = 23), clinical status was quantified with the Clinical Dementia Rating (CDR) scale. Care partners (n = 37) were assigned CDR = 0. Results SATURN and MoCA scores were highly correlated (P < .00001; r = 0.90). CDR sum-of-boxes scores were well-correlated with both tests (P < .00001) (r = -0.83 and -0.86, respectively). Statistically, neither test was superior. Most participants (83%) reported that SATURN was easy to use, and most either preferred SATURN over the MoCA (47%) or had no preference (32%). Discussion Performance on SATURN-a fully self-administered and freely available (https://doi.org/10.5061/dryad.02v6wwpzr) cognitive screening test-is well-correlated with MoCA and CDR scores.
Furthering a partnership: Air quality modeling and improving public health.

Air pollution is one of the top five risk factors for population health globally. In recent years, advances in air pollution data and modeling have occurred simultaneously with advances in data and...
The consistency of prior movements shapes locomotor use-dependent learning

Repetition is an indispensable component of motor skill acquisition. However, it is unknown how consistent repeated movement patterns must be to engage an implicit ‘use-dependent’ learning mechanism. In this Registered Report, we tackled this question through a combination of computational modeling, simulations, and behavioral experiments involving visually-guided treadmill walking. Our hypotheses were formalized by two distinct computational models: In the two-process Strategy plus Use-Dependent model, use-dependent learning is viewed as a slowly updating and slowly decaying bias in the direction of repeated movements. The Adaptive Bayesian model frames use-dependent learning as an emergent property of quickly adapting prior probabilities of target step lengths. Critically, the Adaptive Bayesian model is much more sensitive to variable practice than the Strategy plus Use-Dependent model. To test these hypotheses, human participants (N=18, 10 females) learned a novel asymmetric stepping pattern under three conditions with differing amounts of practice consistency during a learning block. We probed use-dependent movement biases immediately post-learning by asking participants to ‘walk normally’ during a washout block with no visual feedback. We found that the total magnitude of use-dependent learning depended on practice consistency during learning, consistent with the Adaptive Bayesian model. However, this dependence faded quickly as biases became similar in magnitude over subsequent strides across all conditions, an observation more consistent with the Strategy plus Use-Dependent model. Simple post-hoc adjustments to the Strategy plus Use-Dependent model made clear that these seemingly opposing effects of practice consistency can result from a unitary use-dependent learning process shaped by recent movement history. Significance Statement Practice, in the form of movement repetition, is central to motor learning. However, we do not know how consistently a person must move in order to benefit from repeated practice. We aimed to answer this question through a combination of computational modeling and behavioral experiments. We found that the total magnitude of use-dependent learning was dependent on practice consistency, but this dependence faded quickly, leaving a small but sustained aftereffect that is resistant to completely washing out. A simple model that learned only from recent movement history could explain our results. These findings should have broad implications for the study of locomotor learning as repetition is central to both basic locomotor learning and gait rehabilitation studies.
Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells.

Bispecific T-cell engagers (BiTEs) preferentially targeting tumour-associated antigens and stimulating CD3-mediated signalling are being used in patients to treat acute B-cell lymphoblastic leukemia. However, the potency of BiTEs in solid tumours is limited by their short half-life and their severe toxicity at relevant therapeutic doses. Here we report the design and in vivo performance of a bispecific antibody that simultaneously targets the murine T-cell co-receptor CD3e and the murine immune checkpoint programmed-death ligand 1 (PD-L1). In multiple syngeneic tumour models, the bispecific antibody generated higher antitumour immune responses than conventional BiTEs targeting tumour-associated antigens and CD3e. We found that the durable antigen-specific T-cell responses resulted from the rejuvenation of CD8 T cells, owing to the blockade of PD-L1 on dendritic cells (but not on tumour cells) and co-stimulation by B7-1&2 (a peripheral membrane protein on dendritic cells). Bispecific T-cell engagers targeting dendritic cells rather than tumour cells may represent a general means of T-cell rejuvenation for durable cancer immunotherapy. A bispecific antibody targeting the T-cell co-receptor CD3e and the immune checkpoint programmed-death ligand 1 on dendritic cells rejuvenates tumour-specific CD8 T cells, leading to durable antitumour responses in murine models of cancer.
Acetyl-l-carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury

In the present study, we evaluated the therapeutic efficacy of acetyl-l-carnitine (ALC) administration on mitochondrial dysfunction following tenth thoracic level contusion spinal cord injury (SCI) in rats. Initial results from experiments in vitro with naive mitochondria showed that, in the absence of pyruvate, ALC can be used as an alternative substrate for mitochondrial respiration. Additionally, when added in vitro to mitochondria isolated from 24 h injured cords, ALC restored respiration rates to normal levels. For administration studies in vivo, injured rats were given i.p. injections of saline (vehicle) or ALC (300 mg/kg) at 15, 30 or 60 min post-injury, followed by one booster after 6 h. Mitochondria were isolated 24 h post-injury and assessed for respiration rates, activities of NADH dehydrogenase, cytochrome c oxidase and pyruvate dehydrogenase. SCI significantly (p < 0.05) decreased respiration rates and activities of all enzyme complexes, but ALC treatment significantly (p < 0.05) maintained mitochondrial respiration and enzyme activities compared with vehicle treatment. Critically, ALC administration in vivo at 15 min and 6 h post-injury versus vehicle, followed once daily for 7 days, significantly (p < 0.05) spared gray matter. In summary, ALC treatment maintains mitochondrial bioenergetics following contusion SCI and, thus, holds great potential as a neuroprotective therapy for acute SCI.
Back to the Future: Does Apprendi Bar a Legislature's Power to Shift the Burden of Proof Away from the Prosecution by Labeling an Element of a Traditional Crime as an Affirmative Defense?

This Article considers whether it would be sound to extend the Apprendi rule to affirmative defenses. Part II of this Article considers the historical foundation of the Due Process Clause and the evolution of the assignment of the burden of proof for affirmative defenses and sentencing factors. Part II also reviews Mullaney and its progeny through the most current case, Apprendi. Part III discusses the Court's model for determining which categories of statutory language constitute elements requiring proof beyond a reasonable doubt and which are "nonessential element[s] of an offense." Part IV evaluates whether it is appropriate to assign the defendant the burden of proving affirmative defenses to the defendant under the post-Apprendi construct and considers the likelihood and wisdom of returning Mullaney to its full constitutional vigor. Ultimately, this Article concludes that while extending the Apprendi rule to affirmative defenses would not be inconsistent with recent Court decisions, it would be inappropriate because the Court's reasoning for curtailing the legislature's ability to shift the burden of proof for sentence enhancements is not applicable to affirmative defenses.
Impact of Structure and Functionality of Core Polyol in Highly Functional Biobased Epoxy Resins

Highly functional biobased epoxy resins were prepared using dipentaerythritol (DPE), tripentaerythritol (TPE), and sucrose as core polyols that were substituted with epoxidized soybean oil fatty acids, and the impact of structure and functionality of the core polyol on the properties of the macromolecular resins and their epoxy-anhydride thermosets was explored. The chemical structures, functional groups, molecular weights, and compositions of epoxies were characterized using nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, gel permeation chromatography (GPC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI MS). The epoxies were also studied for their bulk viscosity, intrinsic viscosity, and density. Crosslinked with dodecenyl succinic anhydride (DDSA), epoxy-anhydride thermosets were evaluated using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), tensile tests, and tests of coating properties. Epoxidized soybean oil (ESO) was used as a control. Overall, the sucrose-based thermosets exhibited the highest moduli, having the most rigid and ductile performance while maintaining the highest biobased content. DPE/TPE-based thermosets showed modestly better thermosetting performance than the control ESO thermoset.
Diseconomies of Scale

Diseconomies of scale are said to exist when long run average total costs increase because a firm is too large. Keywords: average total cost; economies of scale; minimum efficient scale
Energy outlier detection in smart environments

Despite a dramatic growth of power consumption in households, less attention has been paid to monitoring, analyzing and predicting energy usage. In this paper, we propose a framework to mine raw energy data by transforming time series energy data into a symbol sequence, and then extend a suffix tree data structure as an efficient representation to analyze global structural patterns. Then, we use a clustering algorithm to detect energy pattern outliers which are far from their cluster centroids. To validate our approach, we use real power data collected from a smart apartment testbed during two months.
Bacterial Peptidoglycan-Induced tnf-α Transcription Is Mediated Through the Transcription Factors Egr-1, Elk-1, and NF-κB

Bacteria and their ubiquitous cell wall component peptidoglycan (PGN) activate the innate immune system of the host and induce the release of inflammatory molecules. TNF-α is one of the highest induced cytokines in macrophages stimulated with PGN; however, the regulation of tnf-α expression in PGN-activated cells is poorly understood. This study was done to identify some of the transcription factors that regulate the expression of the tnf-α gene in macrophages stimulated with PGN. Our results demonstrated that PGN-induced expression of human tnf-α gene is regulated by sequences proximal to −182 bp of the promoter. Mutations within the binding sites for cAMP response element, early growth response (Egr)-1, and κB3 significantly reduced this induction. The transcription factor c-Jun bound the cAMP response element site, Egr-1 bound the Egr-1 motif, and NF-κB p50 and p65 bound to the κB3 site on the tnf-α promoter. PGN rapidly induced transcription of egr-1 gene and this induction was significantly reduced by specific mutations within the serum response element-1 domain of the egr-1 promoter. PGN also induced phosphorylation and activation of Elk-1, a member of the Ets family of transcription factors. Elk-1 and serum response factor proteins bound the serum response element-1 domain on the egr-1 promoter, and PGN-induced expression of the egr-1 was inhibited by dominant-negative Elk-1. These results indicate that PGN induces activation of the transcription factors Egr-1 and Elk-1, and that PGN-induced expression of tnf-α is directly mediated through the transcription factors c-Jun, Egr-1, and NF-κB, and indirectly through the transcription factor Elk-1.
Genesis of an Academic Research Program

As students progress towards their PhD degrees, they will become more independent and practitioner-like; for those moving into academia, it is often assumed the programs of their PhD mentors will serve as prototypes for their own successful research programs. However, the author’s research program as an Assistant Professor led him in directions never considered as a graduate student. The author had to make significant decisions in choosing a primary audience, finding an overarching theme, defining the individual problems, and developing these problems into researchable projects. Infrastructurerelated issues associated with the author’s research program were also considered. The details of his journey from the end of his doctoral degree to his current position as an Assistant Professor are described in this article.