cssi/SciSciGPT-SciSciNet huggingface dataset:
The V410M mutation associated with pyrethroid resistance in Heliothis virescens reduces the pyrethroid sensitivity of house fly sodium channels expressed in Xenopus oocytes.

Some strains of Heliothis virescens carry a novel sodium channel mutation, corresponding to the replacement of Val410 by Met (designated V410M) in the house fly Vssc1 sodium channel, that is genetically and physiologically associated with pyrethroid resistance. To test the functional significance of this mutation, we created a house fly Vssc1 sodium channel containing the V410M mutation by site-directed mutagenesis, expressed wildtype and specifically mutated sodium channels in Xenopus laevis oocytes, and evaluated the effects of the V410M mutation on the functional and pharmacological properties of the expressed channels by twoelectrode voltage clamp. The V410M mutation caused depolarizing shifts of |9 mV and |5 mV in the voltage dependence of activation and steady-state inactivation, respectively, of Vssc1 sodium channels. The V410M mutation also reduced the sensitivity of Vssc1 sodium channels to the pyrethroid cismethrin at least 10-fold and accelerated the decay of cismethrin-induced sodium tail currents. The degree of resistance conferred by the V410M mutation in the present study is sufficient to account for the degree of pyrethroid resistance in H. virescens that is associated with this mutation. Although Val410 is located in a sodium channel segment identified as part of the binding site for batrachotoxin, the V410M mutation did not alter the sensitivity of house fly sodium channels to batrachotoxin. The effects of the V410M mutation on the voltage dependence and cismethrin sensitivity of Vssc1 sodium channels were indistinguishable from those caused by another sodium channel point mutation, replacement of Leu1014 by Phe (L1014F), that is the cause of knockdown resistance to pyrethroids in the house fly. The positions of the V410M and L1014F mutations in models of the tertiary structure of sodium channels suggest that the pyrethroid binding site on the sodium channel α subunit is located at the interface between sodium channel domains I and II. © 2001 Elsevier Science Ltd. All rights reserved.
Immunofluorescent Detection of Staphylococcal Enterotoxin B II. Detection in Foods

SUMMARY Specific staphylococcal enterotoxin B anti-serum conjugated with fluorescein isothiocyanate was used successfully for detecting toxin in food smears or food extracts in about 4–5 hr. The fluorescent antibody technique detected minute amounts of enterotoxin—much less than 1 or 0.05 μg/ml, which are the sensitivity limits of single or double gel diffusion tube tests—-without involving any extraction procedures.
LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in Caenorhabditis elegans

A novel mode of crosstalk between the EGFR-Ras-MAPK and LIN-12/Notch pathways occurs during the patterning of a row of vulval precursor cells (VPCs) in Caenorhabditis elegans : activation of the EGFR-Ras-MAPK pathway in the central VPC promotes endocytosis and degradation of LIN-12 protein. LIN-12 downregulation in the central VPC is a prerequisite for the activity of the lateral signal, which activates LIN-12 in neighboring VPCs. Here we characterize cis -acting targeting sequences in the LIN-12 intracellular domain and find that in addition to a di-leucine motif, serine/threonine residues are important for internalization and lysine residues are important for post-internalization trafficking and degradation. We also identify two trans -acting factors that are required for post-internalization trafficking and degradation: ALX-1, a homolog of yeast Bro1p and mammalian Alix and the WWP-1/Su(dx)/Itch ubiquitin ligase. By examining the effects of mutated forms of LIN-12 and reduced wwp-1 or alx-1 activity on subcellular localization and activity of LIN-12, we provide evidence that the lateral signal-inhibiting activity of LIN-12 resides in the extracellular domain and occurs at the apical surface of the VPCs.
Inhibition Versus Switching Deficits in Different Forms of Rumination

Individuals who depressively ruminate about their current dysphoria tend to perseverate more than nonruminators. The goal of the current study was to determine whether such perseverative tendencies are associated with an inability to switch attention away from old to new information or with an inability to effectively inhibit the processing of previously relevant information. We used a task-switching paradigm that can distinguish between these two processes. Two experiments showed that depressive rumination is associated with a deficit in inhibiting prior mental sets. The second experiment also demonstrated that, in contrast to depressive rumination, angry and intellectual rumination are associated with difficulties in switching to a new task set, but not with inhibition of a prior task set. This study suggests that different forms of rumination are associated with different cognitive mechanisms and that both deficits may contribute to the perseveration that is associated with ruminative tendencies.
Organization Development: A Political Perspective

It is now accepted that organizational politics exist in every organization and are involved in almost every facet of organizational life. Organizational politics are certainly involved in intervention programs. Despite these facts, organization development (OD) has been characterized as lacking any political sophistication whatsoever. In order to increase their success rate, OD consultants have been asked to become more politically involved in their intervention programs [Bennis, 1969; Pettigrew, 1975]. We argue here that OD has developed an unrecognized political orientation that aids OD consultants in the political arena and supports their intervention programs, and we explore the practical and ethical/value considerations of greater political involvement.
Antipredator Behaviors of the Red Hills Salamander, Phaeognathus hubrichti

The antipredator behaviors of Phaeognathus hubrichti (Red Hills Salamander), a large fossorial plethodontid, and the basal member of the desmognathine salamanders, are unknown. The responses of P. hubrichti to tongue-flicks from hand-held snakes, tapping with a rod and pinching with a forceps were recorded with a videocamera. When contacted by a snake tongue- flick, P. hubrichti exhibited several antipredator behaviors including immobility, gape, walk, run, head flatten, head elevation, flip, bite, and flinch. One other antipredator behavior—writhe—was observed in the field. The antipredator be- haviors of P. hubrichti are more similar to those species in its sister taxon, Desmognathus, than to those of other less closely related fossorial salamanders. Gape, a threat display, is nearly identical to that of Desmognathus quadramaculatus. Gape, bite, and writhe are proposed to be ancestral behaviors in this group.
Is There a Phase Transition in the Multifractal Spectrum of DLA

The diffusion-limited aggregation1 (DLA) model has been found to describe a remarkably large number of interesting physical systems such as fluid flow in porous media, colloidal aggregation, and electrodeposition.2–17 Although DLA is one of the most important models of fractal growth phenomena, and is described by a quite simple set of rules, we do not understand DLA as completely as we do, say, the two-dimensional Ising model. For example, even the existence of the fractal dimension in the large-cluster limit is not clear. The situation becomes more complicated, since the fractal dimension alone is not sufficient to characterize the growth process.4–6 Furthermore, in order to fully characterize the growth process, one needs an infinite number of independent exponents, which is usually called the multifractal spectrum.7–9
Stochastic Linear Programming and Feasibility Problems in Farm Growth Analysis

If farm growth is defined in terms of asset accumulation, dynamic linear programming techniques can be employed to determine rates of growth implied by nonstochastic models based on assumed farm situations. Frequently, however, because of the environmental conditions in which farms typically operate, a probabilistic characterization of a number of coefficients in such a model is more realistic. With the introduction of these variable coefficients, the programming model used in calculating feasible rates of growth becomes stochastic. There are two alternative methods of solving these stochastic programming models, of which only one, the distribution method, is considered in this article. This method is examined for its usefulness in establishing feasible rates of growth for a particular farm model. An evaluation of the farm growth model and the distribution method of solving the programming problem is then made in relation to a farm representative of an area in the Texas High Plains.
Application of Transformer-Less UPFC for Interconnecting Two Synchronous AC Grids With Large Phase Difference

In this paper, the application of an innovative transformer-less unified power flow controller (UPFC) for interconnecting two synchronous ac grids with large phase difference is presented. The proposed transformer-less UPFC is based on two cascaded multilevel inverters. As is well known, the real power flow between two generators is mainly determined by their phase difference. If two grids with large phase difference are initially separate from each other, once connected, there will be huge current flowing through the transmission line and will, thus, damage the generators or other supplementary equipments. Therefore, to connect two synchronous ac grids with each other without using an extra device is impossible. For decades, researchers have been investigating different approaches to this problem but still difficult to conquer, especially for real hardware implementation. An effective solution using the transformer-less UPFC is demonstrated in this paper. The transformer-less UPFC can realize grid interconnection, independent active and reactive power control, dc-link voltage balance control, etc. Furthermore, a 1-pu equipment can compensate system with phase difference as large as 30°. Experimental results based on the 13.8-kV/ 2-MVA transformer-less UPFC prototype are shown to validate the theoretical analysis.
Interesting case – actionable mutation in a case with a recurrent pleomorphic xanthoastrocytoma with anaplastic features

Pleomorphic xanthoastrocytoma (PXA) is an uncommon low grade astrocytic tumor and molecular alterations commonly observed in other WHO grade II gliomas, such as TP53 mutation, EGFR amplification, 1p19q deletion, are rarely seen. A 25-year-old woman experienced generalized seizures; a left temporal lesion in was identified in 2001. Resections were performed in 2004 and 2011 with a diagnosis of PXA, WHO grade II. The patient was treated with radiation and chemotherapy, but recurrence was found in 2013. The pathology of the craniotomy resection showed tumor necrosis and increased proliferation index (25% by Ki-67), and the diagnosis of PXA with anaplastic features exhibiting leptomeningeal infiltration was rendered, which likely represented malignant transformation. Targeted next-generation sequencing analysis was performed at Genomic Pathology Service (Washington University). A potentially actionable BRAF gene mutation (p.V600E) as well as potentially relevant TP53 gene p.R158H mutation was identified. The patient is on Vemurafenib and the lesion is stable on MRI. PXA has been shown to have BRAF mutations in 60–70% of cases. PXA with anaplastic features is a rare entity and has significantly worse prognosis. Vemurafenib is suggested to cross the blood-brain barrier and the patients with BRAF mutated brain tumors would benefit from BRAF targeted therapies.
Selective Absorption in the Small Intestine

The microvilli of the cells that line the small intestine form a continuous frontier at which membrane digestion takes place. Enzymes and carriers are differentially distributed along the length of the intestine, with corresponding regional differences in the digestion and absorption of foodstuffs and vitamins. Since the presence of essential enzymes and carriers is genetically determined, deficiency diseases may occur; lactase is absent from the adult intestines of whole populations.
Polyethylene-water partitioning coefficients for parent- and alkylated-polycyclic aromatic hydrocarbons and polychlorinated biphenyls.

We report polyethylene (PE)–water partitioning coefficients (KPE) for 17 parent-polycyclic aromatic hydrocarbons (PAHs), 22 alkylated-PAHs, 3 perdeuterated parent-PAHs, and 100 polychlorinated biphenyl (PCB) congeners or coeluting congener groups. The KPE values for compounds in the same homologue group are within 0.2 log units for alkylated-PAHs but span up to an order of magnitude for PCBs, due to the greater contribution of the position of the substituents (i.e., chlorines for PCBs and alkyl groups for alkylated-PAHs) to the molecular structure. The KPE values in deionized water for parent- and alkylated-PAHs show a good correlation with a regression model employing the number of aromatic carbons (CAR) and aliphatic carbons (CAL) in each compound: log KPE = −0.241 + 0.313CAR + 0.461 CAL. The regression model is useful for the assessment of freely dissolved aqueous concentrations of alkylated-PAHs, which comprise a significant fraction of the total in petroleum-derived PAHs and in some pyrogenic PAH mix...
Quantitative Measurement of Ligand Exchange on Iron Oxides via Radiolabeled Oleic Acid

Ligand exchange of hydrophilic molecules on the surface of hydrophobic iron oxide nanoparticles produced via thermal decomposition of chelated iron precursors is a common method for producing aqueous suspensions of particles for biomedical applications. Despite the wide use, relatively little is understood about the efficiency of ligand exchange on the surface of iron oxide nanoparticles and how much of the hydrophobic ligand is removed. To address this issue, we utilized a radiotracer technique to track the exchange of a radiolabeled (14)C-oleic acid ligand with hydrophilic ligands on the surface of magnetite nanoparticles. Iron oxide nanoparticles functionalized with (14)C-oleic acid were modified with poly(ethylene glycol) with terminal functional groups including, L-3,4-dihydroxyphenylalanine, a nitrated L-3,4-dihydroxyphenylalanine, carboxylic acid, a phosphonate, and an amine. Following ligand exchange, the nanoparticles and byproducts were analyzed using liquid scintillation counting and inductively coupled plasma mass spectroscopy. The labeled and unlabeled particles were further characterized by transmission electron microscopy and dynamic light scattering to determine particle size, hydrodynamic diameter, and zeta potential. The unlabeled particles were characterized via thermogravimetric analysis and vibrating sample magnetometry. Radioanalytical determination of the (14)C from (14)C-oleic acid was used to calculate the amount of oleic acid remaining on the surface of the particles after purification and ligand exchange. There was a significant loss of oleic acid on the surface of the particles after ligand exchange with amounts varying for the different functional binding groups on the poly(ethylene glycol). Nonetheless, all samples demonstrated some residual oleic acid associated with the particles. Quantification of the oleic acid remaining after ligand exchange reveals a binding hierarchy in which catechol derived anchor groups displace oleic acid on the surface of the nanoparticles better than the phosphonate, followed by the amine and carboxylic acid groups. Furthermore, the results show that these ligand exchange reactions do not necessarily occur to completion as is often assumed, thus leaving a residual amount of oleic acid on the surface of the particles. A thorough analysis of ligand exchange is required to develop nanoparticles that are suitable for their desired application.
Governing Project Investments

This study proposes an effective governance model for project adjudication and funding that draws from several industries, including financial services and higher education. The goal is to provide senior executives with a proven blueprint for investing in projects that align with strategy, thereby bolstering return on investment (ROI).
Binary geothermal energy conversion systems: Basic Rankine, dual–pressure, and dual–fluid cycles

While a significant portion of the world's geothermal power production comes from higher enthalpy geothermal resources, there is a large resource base of lower-temperature resources that can be developed using the binary cycle technology. This conversion technology both allows for the more efficient conversion of the energy potential of these geothermal fluids into electrical power and provides multiple design options that allow the optimal combination of cost and performance. This design flexibility maybe be the deciding factor as to whether a project is commercially viable. This chapter provides an overview of the binary cycle and some of the design options that are available. A brief discussion is included as to how the selection of the different options available impacts both the plant performance and cost of the project.
Measuring of phosphorous in silicon wafers by VPD-ICPMS

Phosphorus is typically a common dopant used in wafer manufacturing. Measuring of phosphorous in Si-wafer is always demanding and matrix interferences is always a problem in VPD ICPMS. It is reported here the measuring of phosphorus in VPD matrix using ICPMS.
The Die Is Cast: Precision Electrophilic Modifications Contribute to Cellular Decision Making.

This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins. The latest interrogations into these on-target electrophilic responses set forth a new horizon in the molecular mechanism of redox signal propagation wherein direct low-occupancy electrophilic modifications on a single sensor target are biologically sufficient to drive functional redox responses with precision timing. We detail how the various mechanisms through which redox signa...
Somatic GNAQ Mutation is Enriched in Brain Endothelial Cells in Sturge–Weber Syndrome

Abstract Background Sturge–Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial and extracraniofacial capillary malformations and capillary-venule malformations in the leptomeninges. A somatic mosaic mutation in GNAQ (c.548G>A; p.R183Q) was found in SWS brain and skin capillary malformations. Our laboratory showed endothelial cells in skin capillary malformations are enriched for the GNAQ mutation. The purpose of this study is to determine whether the GNAQ mutation is also enriched in endothelial cells in affected SWS brain. Methods Two human SWS brain specimens were fractionated by fluorescence-activated cell sorting into hematopoietic (CD45), endothelial (CD31, VE-Cadherin, and vascular endothelial growth factor receptor 2), and perivascular (platelet-derived growth factor receptor beta) cells and cells negative for all markers. The sorted cell populations were analyzed for GNAQ p.R183Q mutation by droplet digital polymerase chain reaction. SWS patient-derived brain endothelial cells were selected by anti-CD31-coated magnetic beads and cultured in endothelial growth medium in vitro . Results The GNAQ p.R183Q mutation was present in brain endothelial cells in two SWS specimens, with mutant allelic frequencies of 34.7% and 24.0%. Cells negative for all markers also harbored the GNAQ mutation. The mutant allelic frequencies in these unidentified cells were 9.2% and 8.4%. SWS patient-derived brain endothelial cells with mutant allelic frequencies of 14.7% and 21% survived and proliferated in vitro . Conclusions Our study provides evidence that GNAQ p.R183Q mutation is enriched in endothelial cells in SWS brain lesions and thereby reveals endothelial cells as a source of aberrant Gαq signaling. This will help to understand the pathophysiology of SWS, to discover biomarkers for predicting cerebral involvement, and to develop therapeutic targets to prevent neurological impairments in SWS.
Blue Man Group no ASSIN: Usando Representações Distribuídas para Similaridade Semântica e Inferência Textual

In this paper, we present the methodology and the results obtained by our team, dubbed Blue Man Group, in the ASSIN (from the Portuguese Avaliacao de Similaridade Semântica e Inferencia Textual) competition, held at PROPOR 2016. Our team's strategy consisted of evaluating methods based on semantic word vectors, following two distinct directions: 1) to make use of low-dimensional, compact, feature sets, and 2) deep learning-based strategies dealing with high-dimensional feature vectors. Evaluation results demonstrated that the first strategy was more promising, so that the results from the second strategy have been discarded. As a result, by considering the best run of each of the six participant teams, we have been able to achieve the best accuracy and F1 values in entailment recognition, in the Brazilian Portuguese set, and the best F1 score considering also the Portuguse from Portugal set. In the semantic similarity task, our team was ranked second in the Brazilian Portuguese set, and third considering both sets.
Crowdsourced tDCS Research: Feasible or Fanciful?

In recent years, there has been an increase in “crowdsourced” health studies, wherein patients and individuals are not merely passive subjects, but rather active participants in driving research (S...
Timing of transcriptomic and proteomic changes in the bovine placentome after parturition.

Proper post-partum reproductive performance is important for reproductive efficiency in beef cows, and dystocia decreases post-partum fertility. Crossbred beef cows (n = 1676) were evaluated for lifetime performance based on degree of dystocia at presentation of the first calf. Cows that experienced moderate or severe dystocia produced fewer calves during their productive life (P < 0.01). The exact mechanism is unclear, but may be due to the contributions of dystocia to abnormal placental separation. Proteolytic activity is hypothesized to contribute to placental separation in ruminants; however, when ovine placentomes were collected following caesarian section, no proteolytic activity was detected. We hypothesized that stage 2 of parturition was necessary to stimulate proteolysis and initiate placental separation. Serial placentome collections were performed on mature cows (n = 21 initiated; 7 with complete sampling) at hourly intervals for the first 2 h after expulsion of the calf. An intact piece of each placentome was fixed for histological evaluation, and a separate piece of caruncular and cotyledonary tissue from each placentome was frozen for transcriptomic and proteolytic analysis. A full set of placentomes was collected from only 7 of 21 cows at 0, 1, and 2 h, and all cows had expelled fetal membranes by 6 h. Histological, transcriptomic and proteolytic analysis was performed on placentomes from cows from which three placentomes were collected (n = 7). The microscopic distance between maternal and fetal tissues increased at 1 h (P = 0.01). Relative transcript abundance of matrix metalloprotease 14 (MMP14) tended to increase with time (P = 0.06). The relative transcript abundance of plasminogen activator urokinase-type (PLAU) was greater in caruncles than cotyledons (P = 0.01), and tended (P = 0.10) to increase in the caruncle between 0 and 2 h while remaining unchanged in the cotyledon over the same span of time. Greater PLAU and plasminogen activator tissue-type (PLAT) proteolytic activity was detected by zymography in the caruncle than the cotyledon immediately post-partum (P < 0.01). From these findings we conclude that 1) dystocia during the first parity decreases lifetime productivity in beef cattle, 2) the PA system is present at both the transcript and protein level in the bovine plactentome during parturition and 3) proteolytic activity is localized to the caruncular aspect of the placentome.
Revealing the Design Process: Inventing a Meta-Analysis Method for Documenting the Fashion Design Process

How designers think throughout the creative process is one of the major issues in the field of design. This study aims to introduce a meta-analysis method that documents and analyses the idea devel...
Parental Homework Completion and Treatment Knowledge During Group Parent–Child Interaction Therapy

The purpose of this study was to examine how parental homework completion, session attendance, and treatment knowledge influenced parenting practices and confidence in using learned skills during behavioral parent training (BPT). Parents of 54 preschoolers (Mage = 5.07, 82% Hispanic/Latino) with externalizing behavior problems participated in an 8-week group BPT program. Pre-and posttreatment measures included parent-reported parenting practices and a treatment knowledge quiz. Parental homework completion, or home practice of skills, was reported by parents and collected weekly. Increases in positive parenting and decreases in negative parenting were observed (Cohen’s d = .63 and .70, respectively), as well as increases in treatment knowledge (d = 1.46). Treatment knowledge moderated the association between parental homework completion and negative parenting as well as parenting skill-use confidence. Increased parental homework completion was only associated with decreases in negative parenting and increa...
Membrane estrogen receptors signal to determine transcription factor function.

Abstract Estrogen receptors (ER) alpha and beta as well as many other steroid receptors are found both within the nucleus and outside the nucleus. This includes extra-nuclear receptors in many organelles, including mitochondria, endoplasmic reticulum, cytosolic endosomes, and membrane lipid rafts, such as caveolae. The functions of these receptors in the various extra-nuclear cell organelles are not well described, but progress for understanding steroid receptor signaling from the membrane has advanced. In this Review I will discuss the enlarging role of membrane ER signaling to the expression, cell localization, and function of transcription factors that are essential to mediate cell physiology or pathophysiology in many organs.
Phosphorus Transport in Lake Erie

The role of phosphorus as a causal factor in the eutrophication of Lake Erie is reviewed and the phosphorus budget analyzed. Recent studies by others provide quantitative estimates of the phosphorus loading to Lake Erie. In 1975 the total phosphorus loading to the lake was estimated to be 35,307 metric tons—3 percent from the atmosphere, 43 percent from shoreline erosion, 7 percent from the Lake Huron outflow, 24 percent from point sources within the Lake Erie drainage basin, and 25 percent from diffuse sources in the Lake Erie drainage basin. The above estimates are assumed to include phosphorus in all of its forms, i.e. total phosphorus. The disposition of total phosphorus in Lake Erie includes a mean value of 879 mg/kg in the sediments (based on dry sediment weight) and a mean value of 0.026 g/m3 in the water column (although there were significant variations with position in the lake).
Preparation of counsellors in Pakistan: A proposed model

This paper proposes a comprehensive counselor preparation model within the philosophical and religious beliefs of Pakistan. A series of courses are presented to provide a cohesive and comprehensive body of knowledge to counselors to work in educational, business, health and community settings. The proposed curriculum reflects the philosophy, beliefs, and values of the country in terms of human development, life/career and educational planning. Furthermore, this model proposes a pre-service preparation to replace the current in-service preparation model for counselors.
Administration and Asean Regionalism

What is our state of knowledge on the administration of regionalism in the ASEAN? The deepening integration of the Southeast Asian region in terms of economics and politics has reached some significant points such as the passage of the ASEAN Charter, implementation of AFTA and the advancing of envisioned communities such as the Economic Community, Political Security Community and the Socio-Cultural Community. However, a most glaring gap is the non-existence of provisions for implementation, monitoring and evaluation of ASEAN policies. These activities are for the most part the functions of a civil service or public administration. This lack of a bureaucracy is problematic since the call for good governance in ASEAN means that there must be continuity, accountability, transparency and predictability not only in policymaking but also in policy implementation and its concomitant activities. While bureaucracies can challenge political actors for power, nation-states have still built and sustained them for continuity in policy. Political actors come and go but without the institutional memory of a bureaucracy, governments can sometimes fail to appreciate the whole context of a given policy. In the context of the ASEAN, there is a need to know how its Secretariat has been working in the past as well as its prospects for the future. The lack of a strong ASEAN Secretariat has wide implications on the political thought of ASEAN member-states since it can be argued that this is a way of ensuring that there will not be another avenue for political competition on policy matters. To further refine this debate, it is important to look into the literature on what has been written about the ASEAN Secretariat and its prospects for the future. An institutionalist perspective on this would provide considerable insight on ASEAN’s “way of doing things.”
Abstract LB-A21: PRAS40 (AKT1S1) ablation modulates breast cancer by increasing tumor-free survival in HER-2/neu overexpressing mice

HER-2 is over-expressed in around 20% of breast cancer patients and is correlated with a shorter relapse time and poor prognosis. This makes it crucial to identify novel downstream molecular targets in spite of a number of clinically approved drugs that target HER-2. In this study, we determined if loss of proline-rich Akt substrate of 40 kDa (PRAS40) gene increases tumor-free survival in HER-2/neu over-expressing double transgenic mice. Tumor kinetics was determined in HER-2 overexpressing PRAS40+/+ (wild-type) versus PRAS40-/- (knock-out) mice. Mammary intraepithelial neoplasias (MINs or precancerous lesions) in mammary tissues were analyzed using whole mount analysis. We observed significant increase of tumor-free survival in HER-2 overexpressing PRAS40-/- versus PRAS40+/+ parous female mice, however this effect was not significant in virgin mice. In virgin mice, we observed post-menopausal switch of tumor-free survival. The pre-menopausal protection from mammary tumors could be due to presence of Estrogen (ER). Irrespective of parity, we observed significant reduction of mammary intraepithelial neoplasias (MINs or precancerous lesions) in PRAS40-/- versus PRAS40+/+ mice. To investigate the mechanism of action of ER in HER-2 over-expressing mice we treated ER positive cells with Doxorubicin, ER or the combination in vitro. Modulation of cell proliferation and apoptosis was determined by PRAS40 transient knockdown (siPRAS40) versus non-targeting (NT) following treatment in ER positive ZR-751 cells. To interrogate the effect of Doxorubicin, ER, in vitro, cell lines were treated with 6-24 hr Doxorubicin, ER or both. Doxorubicin, ER or combination treatment led to significant reduction in proliferation and increased apoptosis in siPRAS40 versus non-targeting (NT) ZR-751 cells. Together, our data suggests that ER may have an effect upon PRAS40 knockdown in vitro and in vivo. Our results show that PRAS40 could be a novel ‘druggable’ target for treating aggressive HER-2 positive breast cancers. Citation Format: Ritu Malla, Jesika S. Faridi. PRAS40 (AKT1S1) ablation modulates breast cancer by increasing tumor-free survival in HER-2/neu overexpressing mice [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A21.
Cognitive Science Foundations of Integer Understanding and Instruction

This chapter considers psychological and neuroscience research on how people understand the integers, and how educators can foster this understanding. The core proposal is that new, abstract mathematical concepts are built upon known, concrete mathematical concepts. For the integers, the relevant foundation is the natural numbers, which are understood by reference to a mental number line (MNL). The integers go beyond the natural numbers in obeying the additive inverse law: for any integer x, there is an integer −x such that x + (−x) = 0. We propose that practicing applying this law, such as when students learn that the same quantity can be added or subtracted from both sides of an equation, transforms the MNL. In particular, perceptual mechanisms for processing visual symmetry are recruited to represent the numerical symmetry between the integers x and −x. This chapter reviews psychological and neuroscience evidence for the proposed learning progression. It also reviews instructional studies showing that the hypothesized transformation can be accelerated by novel activities that engage symmetry processing compared to conventional activities around number lines and cancellation. Ultimately, these instructional insights can guide future psychological and neuroscience studies of how people understand the integers in arithmetic and algebraic contexts.
Endometrial Tumor Immune Response: Predictive Biomarker of Response to Immunotherapy

The tumor-specific immune response in endometrial cancer is variable within molecular subtypes. Thus, the tumor immune response offers a novel biomarker, separate from molecular subtypes, to predict which patients might respond to immunotherapy.See related article by Talhouk et al., p. 2537.
Co-opting evo-devo concepts for new insights into mechanisms of behavioural diversity.

ABSTRACT We propose that insights from the field of evolutionary developmental biology (or ‘evo-devo’) provide a framework for an integrated understanding of the origins of behavioural diversity and its underlying mechanisms. Towards that goal, in this Commentary, we frame key questions in behavioural evolution in terms of molecular, cellular and network-level properties with a focus on the nervous system. In this way, we highlight how mechanistic properties central to evo-devo analyses – such as weak linkage, versatility, exploratory mechanisms, criticality, degeneracy, redundancy and modularity – affect neural circuit function and hence the range of behavioural variation that can be filtered by selection. We outline why comparative studies of molecular and neural systems throughout ontogeny will provide novel insights into diversity in neural circuits and behaviour.
Full-fledged SABR through Markov Chains

We present a general purpose technique for the efficient and accurate valuation of options in the shifted Stochastic Alpha Beta Rho (shifted-SABR) model which includes SABR as a special case. The method is based on a novel double-layer continuous-time Markov chain (CTMC) from which closed-form matrix expressions for European options are derived. We also propose a recursive risk-neutral valuation technique for pricing discretely monitored path-dependent options, and use it to price Bermudan and barrier options. In addition, we provide single Laplace transform formula for discretely monitored arithmetic Asian options. Numerical experiments confirm the accuracy and efficiency of the proposed method, which is suitable for practical use.
Does avatar identification make unjustified video game violence more morally consequential

Video games can be morally consequential, with immoral in-game behavior affecting moral outcomes, but less is known about what may amplify these effects. Avatar identification is one potential mode...
Investigating Whether Contacting Absent Students Increases Course Success.

Studies suggest that student attendance in college classes increases course success. Yet, surprisingly few studies have examined strategies to increase student attendance. The goal of the current study is to consider whether contacting consistently absent students increases success in an undergraduate research methods course. Results of this classroom action study suggest that students view contacts positively and a majority stated that they were more likely to attend class following the contact. In regression analyses, however, net of other factors such as prior grade point average, contacts did not predict final grade percentage and D/F rate comparisons to a prior semester without contacts showed modest but not statistically significant improvements. Implications are discussed. It is commonly assumed that higher student attendance increases the likelihood that students will succeed in the course, and some research supports this notion. One common strategy for increasing attendance is a mandatory attendance policy and a few studies suggest that such policies increase attendance. Another strategy is for the instructor to systematically contact absent students in an effort to bolster students' feelings of connectedness and increase motivation to attend class. The goal of the current classroom action study is to examine whether contacting consistently absent students increases success in an undergraduate research methods course. 2 Results suggest mixed support for the effectiveness of contacting absent students. Survey results suggest that students generally view the instructor contacts positively and a majority of contacted students stated that the contact made them more likely to come to class. Regression analyses, however, did not suggest any independent impact of the contacts on final course grade, net of other factors such as prior grade point average (GPA). A comparison of D/F rates with a prior section without systematic contacts showed small but not statistically significant improvements in course success compared to a prior semester. The implications of the current study for future research and classroom attendance policies are discussed.
Photolysis of 5-Azido-3-Phenylisoxazole at Cryogenic Temperature: Formation and Direct Detection of a Nitrosoalkene

To enhance the versatility of organic azides in organic synthesis, a better understanding of their photochemistry is required. Herein, the photoreactivity of azidoisoxazole 1 was characterized in cryogenic matrices with IR and UV-Vis absorption spectroscopy. The irradiation (λ = 254 nm) of azidoisoxazole 1 in an argon matrix at 13 K and in glassy 2-methyltetrahydrofuran (mTHF) at 77 K yielded nitrosoalkene 3. Density functional theory (DFT) and complete active space self-consistent field (CASSCF) calculations were used to aid the characterization of nitrosoalkene 3 and to support the proposed mechanism for its formation. It is likely that nitrosoalkene 3 is formed from the singlet excited state of azidoisoxazole 1 via a concerted mechanism or from cleavage of an intermediate singlet nitrene that does not undergo efficient intersystem crossing to its triplet configuration.
Glutathione S-transferases variants as risk factors in Alzheimer's disease.

Glutathione S-transferase (GST) was suggested as an important contributor to Alzheimer’s disease (AD). The GSTs polymorphisms have been investigated as candidate genetic risk factors for AD, yet results remained uncertain. Therefore, we performed a meta-analysis to clarify the relationship of GSTs polymorphisms with the occurrence of AD. PubMed, Embase, Cochrane library and Alzgene databases were searched and potential literatures were selected. Pooled analyses and subgroup analyses were conducted, and also publication bias tests and cumulative meta-analysis. This meta-analysis suggested null associations between polymorphisms of GSTM1, GSTT1, GSTM3, GSTP1, GSTO1 and AD risk. GSTs variants may not have an impact on the morbidity of Alzheimer’s disease. Further well designed researches are required to confirm these findings of the current study.
FDA analysis: Impact of BMI on efficacy outcomes in multiple myeloma trials.

8543Background: Obesity has been implicated as a risk factor for the development of certain types of cancers, including multiple myeloma. Previous studies in other tumor types suggest that overweig...
Abuse of older women in the United States: A review of empirical research, 2017–2019

Abstract This article presents the results of a review of literature on abuse of older women. A systematic search was conducted in five electronic databases for empirical articles published from 2017 through 2019. Of the 727 articles initially captured, 20 articles met the inclusion criteria for review. Across the 20 articles, four primary focal areas emerged: prevalence and incidence of abuse, type of abuse, at-risk populations, and health outcomes. Most of the studies addressed issues identified in prior publications as the study authors attempted to untangle previous findings, expand study samples, and employ novel approaches to data collection. Only 5 articles focused specifically on abuse experienced by older women; older women comprised at least 50% of the sample in each of the other articles. In the latter studies, when gender was included as a study variable, the study authors reported few differences between older women and men with respect to risk factor for and outcomes of abuse. More gender-specific research is needed to better understand the circumstances and outcomes of older women's lived experiences and to inform the development of preventive strategies and gender-sensitive interventions for mitigating elder abuse.
"There Are so Many Nuances . . . ": Health Care Providers' Perspectives of Pain Communication With Hmong Patients in Primary Care Settings.

IntroductionWhile researchers have studied Hmong patients with limited English proficiency in pain communication, no research has examined primary care providers’ (PCPs’) interpretation of Hmong pa...
The Potentially Damaging Effects of Developmental Aid and Voluntourism on Cultural Capital and Well-Being

In this perspective article, we argue that too often, foreign and developmental aid devolves into a form of imperialism and colonialism that we more fully define in the article. We believe that aided communities and community members are often expected (or required) to change their own cultural ways of living to continue receiving the aid or support they have been offered and may need. Ironically, the need for this aid is often driven by the way the aid is provided, creating potential cycles of imperialism and dependency, which can negatively impact individual and community well-being. Fortunately, better practices and ethical guidelines are available to direct the ways that both providers and receivers – communities and individuals – of aid are fully engaged in the process to ensure that all people benefit while being able to continue to live according to their own cultural worldviews. This perspective article provides our ideas about better practices and ethical guidelines for how community development professionals, psychologists, and other behavioral scientists who engage in international aid (in any of its forms) do so in ethical and appropriate ways.
Special Issue Editorial: Current Advances in Liquid Crystals.

The broad field of liquid crystals (LCs) has attracted the attention of chemists, physicists, biologists and engineers alike since the discovery of liquid crystalline phase by the Austrian botanist Friedrich Reinitzer in 1888 [...]
Lagrangian Fluid Dynamics

Part I. The Lagrangian Formulation: 1. Lagrangian kinematics 2. Lagrangian statistics 3. Lagrangian dynamics 4. Coordinates 5. Real fluids Part II. Lagrangian Flows: 6. Some analytical Lagrangian solutions 7. Waves, instabilities and vortices 8. Viscous incompressible flow 9. General solvability Part III. Diffusion: 10. Absolute dispersion 11. Relative dispersion 12. Convective subranges, scalar variance spectrum 13. Diffusion Part IV. Lagrangian Data: 14. Observing systems 15. Data analysis: the single particle 16. Data analysis: particle clusters References.
LERS—A Data Mining System

LERS (Learning from Examples based on Rough Sets) is a Data Mining system inducing rules from raw data sets. For rule induction LERS uses two approaches: machine learning and knowledge acquisition. In the former approach, induced rule sets are discriminant; in the latter, LERS attempts to induce all potential rules hidden in the data set. LERS accepts input data that are erroneous, have numerical attributes, missing attribute values, and / or incosistent. The system has been used in medicine, nursing, global warming, environmental protection, natural language, data transmission, etc. LERS may process big data sets and frequently outperforms not only other rule induction systems but even human experts.
Evidence on the Value of Director Monitoring: A Natural Experiment

I examine the determinants and implications of the level of director monitoring. I use the distance between directors’ domiciles and firm headquarters as a proxy for the level of monitoring and the introduction of a new airline route between director domicile and firm HQ as an exogenous shock to the level of monitoring. I find a strong relation between distance and both board meeting attendance and director membership on strategic versus monitoring committees. Increased monitoring, as measured by a reduction in effective distance, by way of addition of a direct flight, is associated with a 3% reduction in firm value. A reduction in effective distance is also associated with less risk-taking, lower stock return volatility, lower accounting return volatility, lower R&D spending, fewer acquisitions, and fewer patents.
Decentralized output feedback polynomial control of seismically excited structures using genetic algorithm

SUMMARY This paper presents novel decentralized output feedback control strategy for the active and semi-active controls of the highway bridge benchmark phases I and II problems subjected to earthquake ground motions. The control force is calculated using two third-order polynomial equations expressing a direct relationship between displacement and velocity of the control device and the control force. An advanced implicit redundant representation genetic algorithm is utilized to determine optimal coefficients of the two polynomial equations by minimizing the sum of three evaluation criteria for six prescribed earthquakes. The performance of the proposed controller is evaluated in terms of a set of prescribed 21 evaluation criteria and is compared with the other several control strategies published in the special issue of the benchmark problem. The results show that the proposed decentralized output feedback polynomial control strategy can achieve significant response reductions in the bridge system, and it is evidently superior to sample control strategies and other suggested active and semi-active controls for the phase I problem and is quite competitive with respect to the sample and other semi-active control approaches for the fully isolated phase II problem. Copyright © 2011 John Wiley & Sons, Ltd.