cssi/SciSciGPT-SciSciNet huggingface dataset:
The Agrobacterium tumefaciens CheY-like protein ClaR regulates biofilm formation

The switch from a motile, planktonic existence to an attached biofilm is a major bacterial lifestyle transition that is often mediated by complex regulatory pathways. In this report, we describe a CheY-like protein required for control of the motile-to-sessile switch in the plant pathogen Agrobacterium tumefaciens. This regulator, which we have designated ClaR, possesses two distinct CheY-like receiver (REC) domains and is involved in the negative regulation of biofilm formation, through production of the unipolar polysaccharide (UPP) adhesin and cellulose. The ClaR REC domains share predicted structural homology with characterized REC domains and contain the majority of active site residues known to be essential for protein phosphorylation. REC1 is missing the conserved aspartate (N72) residue and although present in REC 2 (D193), it is not required for ClaR-dependent regulation suggesting that phosphorylation, which modulates the activity of many CheY-like proteins, appears not to be essential for ClaR activity. We also show that ClaR-dependent negative regulation of attachment is diminished significantly in mutants for PruA and PruR, proteins known to be involved in a pterin-mediated attachment regulation pathway. In A. tumefaciens, pterins are required for control of the intracellular signal cyclic diguanylate monophosphate through the DcpA regulator, but our findings suggest that pterin-dependent ClaR control of attachment can function independently from DcpA, including dampening of c-di-GMP levels. This report of a novel CheY-type biofilm regulator in A. tumefaciens thus also adds significant details to the role of pterin-mediated signalling.
First-row transition metal–pyridine (py)–sulfate [(py)xM](SO4) complexes (M = Ni, Cu and Zn): crystal field theory in action

The crystal structures of three first-row transition metal-pyridine-sulfate complexes, namely catena-poly[[tetrakis(pyridine-κN)nickel(II)]-μ-sulfato-κ2O:O'], [Ni(SO4)(C5H5N)4]n, (1), di-μ-sulfato-κ4O:O-bis[tris(pyridine-κN)copper(II)], [Cu2(SO4)2(C5H5N)6], (2), and catena-poly[[tetrakis(pyridine-κN)zinc(II)]-μ-sulfato-κ2O:O'-[bis(pyridine-κN)zinc(II)]-μ-sulfato-κ2O:O'], [Zn2(SO4)2(C5H5N)6]n, (3), are reported. Ni compound (1) displays a polymeric crystal structure, with infinite chains of NiII atoms adopting an octahedral N4O2 coordination environment that involves four pyridine ligands and two bridging sulfate ligands. Cu compound (2) features a dimeric molecular structure, with the CuII atoms possessing square-pyramidal N3O2 coordination environments that contain three pyridine ligands and two bridging sulfate ligands. Zn compound (3) exhibits a polymeric crystal structure of infinite chains, with two alternating zinc coordination environments, i.e. octahedral N4O2 coordination involving four pyridine ligands and two bridging sulfate ligands, and tetrahedral N2O2 coordination containing two pyridine ligands and two bridging sulfate ligands. The observed coordination environments are consistent with those predicted by crystal field theory.
The Processing of Homicides in the Courts: An Examination of Multiple Case Outcomes:

The current study employs focal concerns theory to address the role that race/ethnicity plays on various court dispositions of homicide offenders in Newark, NJ, a location where the majority of res...
Characterization of profunda femoris vein thrombosis

Abstract Objective The incidence of and risk factors for profunda femoris vein (PFV) thrombosis are poorly characterized. We prospectively identified patients with PFV deep venous thrombosis (DVT) to characterize the demographics and anatomic distribution of proximal DVT in patients with PFV DVT. Methods A prospective study was conducted of patients at a tertiary care university hospital with DVT diagnosed by venous duplex ultrasound scanning between June 2014 and June 2015. DVT patients were categorized as having PFV involvement (yes or no), and the anatomic distribution of other sites of ipsilateral venous thrombi was further stratified to determine whether there was external iliac vein (EIV), common femoral vein (CFV), or femoropopliteal vein (FPV) DVT. Demographic characteristics of the patients were compared between groups, PFV DVT vs proximal DVT without PFV DVT. Results Of 4584 lower extremity venous duplex ultrasound studies performed, 398 (8.7%) scans were positive for proximal DVT from 260 patients; 23.1% of patients with DVT (60/260) had DVT involving the PFV. Of 112 patients who had CFV DVT, 55 (49.1%) also had ipsilateral involvement of the PFV. Of 60 patients with PFV DVT, 55 (91.7%) had involvement of the ipsilateral CFV. Patients in the PFV DVT group were more likely to have a history of a hypercoagulable disorder (26.7% vs 14.5%; P = .029) and a history of immobility (58.3% vs 42%; P = .026) compared with those with proximal DVT without PFV DVT. There were no differences in smoking, recent surgery, personal or family history of DVT, other medical comorbidities, inpatient status, or survival. There was no difference in laterality of DVT between the PFV DVT and proximal DVT without PFV DVT groups (35% vs 41.5% left, 35% vs 33.5% right, 30% vs 25% bilateral; P = .619). There was a higher proportion of PFV DVT with EIV involvement (21.7% vs 2.5%; P Conclusions Patients with PFV thrombosis tend to have more thrombus burden with more frequent concurrent DVT in the EIV and FPV. Patients with PFV DVT are also more likely to have a history of hypercoagulable disorder and immobility. Ultrasound protocols for assessment of DVT should include routine examination of the PFV as a potential marker of a more virulent prothrombotic state.
Shock tube study of the rate constants for H + O2 + M → HO2 + M (M = Ar, H2O, CO2, N2) at elevated pressures

Abstract The rate constants for the reaction H + O2+ M→HO2+ M were investigated at elevated pressures from 12 to 33 atm using ignition delay time (IDT) measurements behind reflected shock waves in H2/O2/M mixtures with different collision partners M = Ar, H2O, N2 and CO2. The temperature and pressure ranges where the rate constants of the reactions H + O2+ M→HO2+ M and H + O2- > OH + O dominate the IDT sensitivity were selected as optimum test conditions using the detailed H2/O2 mechanism of Hong et al. (2011). The current study thus provides a quantitative and relatively direct method for determining the rate constants for H + O2+ M→HO2+ M using simple IDT measurements. The rate constants found are consistent with earlier studies, but with reduced uncertainties.
Using Portfolios for Large-Scale Assessment

Publisher Summary This chapter discusses the use of portfolios for large-scale assessment. In recent years, educational policy makers have expressed growing concern about the quality of traditional large-scale testing programs and their possible negative effects on curriculum and instruction. Increasing numbers of educators believe greater emphasis on portfolios rather than multiple-choice tests can improve state testing efforts. Portfolio advocates argue that such a change will both increase the validity of state testing programs and improve their value to schools. They believe the addition of genuine student work products into the formal assessment system will increase confidence in the inferences drawn from testing results. The chapter examines the current research on portfolio assessment and considers the strengths and weaknesses of portfolios for large-scale assessment. Such an assessment has various advantages, which are discussed here. Finally, it outlines the potential for portfolio use in large-scale assessment. And the discussion concludes that portfolios will have to be altered and upgraded as per the needs of the teachers. In the coming times, these needs may play into the strengths of portfolios and it may be as classroom assessment tools that portfolio assessments realize their greatest potential.
The Impact of Instrumentation on Analytical Chemistry

In 1985, it is hard for anyone to remember, and most analytical chemists have never known, an instrumentationless world. When one enters a modern analytical laboratory, one is surrounded by equipment so that the analyst may be dwarfed by the instruments at his or her command. Contrast this with the laboratory of the 1930’s; the analyst was surrounded by chemical reagents and the most conspicuous installation was a fume hood. Several drawers contained the tools of the profession — beakers, filters, burets and pipets.
Evaluation of Commercial Bell Pepper Cultivars for Resistance to Phytophthora Blight (Phytophthora capsici)

Phytophthora blight (Phytophthora capsici) is an important disease of bell peppers, causing crown, root, and fruit rot as well as foliar lesions. Substantial yield losses can result from either plant death or fruit rot. Host resistance is an effective management strategy for the root and crown rot phase of the disease, and a number of commercially-available pepper cultivars are described by the supplier as intermediately resistant. In field trials conducted over 5 years, the bell pepper cultivars Archimedes, Aristotle, Intruder, and Paladin were found to be the most resistant to a single isolate of P. capsici from New York State (NY 0664-1). Cultivars ACR285, Declaration, PS 09941819, Revolution, and Vanguard showed intermediate levels of resistance. Escalade, Karisma, Keystone Giant, King of the North, and Red Knight were highly susceptible to NY 0664-1. This information will be useful to growers selecting cultivars to plant in fields with a history of Phytophthora blight.
Process Synthesis under Seasonal and Daily Variability: Application on Concentrating Solar Power

Abstract We propose an optimization-based framework for the synthesis of systems that are subject to variability in two frequencies. We use “scenarios” and “modes” to represent seasonal and daily variability respectively. We construct a multimode superstructure to consider different flowsheets alternatives for each mode. We formulate the optimization problem as a two-stage multimode stochastic programming approach with embedded models in each scenario. We illustrate the applicability of our framework through the design of concentrating solar power (CSP) plants.
Not Just “Over There”: Theater of the Real and Iraqi Voices

This chapter examines theater of the real about the Iraq War. Theater of the real focuses on personal narrative, yet this impulse to understand the lived experiences of the war seldom extends past US borders. Nevertheless, there are a handful of important theater of the real pieces that foreground Iraqi voices. Despite many rigorous studies of theater of the real and its focus on the war on terror, plays about Iraqi experiences have received scant critical attention; scholars, too, are guilty of avoiding Iraqi perspectives. This chapter looks at plays that focus on non-US, non-UK perspectives, particularly George Packer’s Betrayed, Jessica Blank and Erik Jensen’s Aftermath, and Heather Raffo’s 9 Parts of Desire.
Intracochlear Electrocochleography: Response Patterns During Cochlear Implantation and Hearing Preservation.

Objectives Electrocochleography (ECochG) obtained through a cochlear implant (CI) is increasingly being tested as an intraoperative monitor during implantation with the goal of reducing surgical trauma. Reducing trauma should aid in preserving residual hearing and improve speech perception overall. The purpose of this study was to characterize intracochlear ECochG responses throughout insertion in a range of array types and, when applicable, relate these measures to hearing preservation. The ECochG signal in cochlear implant subjects is complex, consisting of hair cell and neural generators with differing distributions depending on the etiology and history of hearing loss. Consequently, a focus was to observe and characterize response changes as an electrode advances. Design In 36 human subjects, responses to 90 dB nHL tone bursts were recorded both at the round window (RW) and then through the apical contact of the CI as the array advanced into the cochlea. The specific setup used a sterile clip in the surgical field, attached to the ground of the implant with a software-controlled short to the apical contact. The end of the clip was then connected to standard audiometric recording equipment. The stimuli were 500 Hz tone bursts at 90 dB nHL. Audiometry for cases with intended hearing preservation (12/36 subjects) was correlated with intraoperative recordings. Results Successful intracochlear recordings were obtained in 28 subjects. For the eight unsuccessful cases, the clip introduced excessive line noise, which saturated the amplifier. Among the successful subjects, the initial intracochlear response was a median 5.8 dB larger than the response at the RW. Throughout insertion, modiolar arrays showed median response drops after stylet removal while in lateral wall arrays the maximal median response magnitude was typically at the deepest insertion depth. Four main patterns of response magnitude were seen: increases > 5 dB (12/28), steady responses within 5 dB (4/28), drops > 5 dB (from the initial response) at shallow insertion depths ( 5 dB occurring at deeper depths (5/28). Hearing preservation, defined as 0.57, maximum of 0.80 for the maximal response). Conclusions Monitoring the cochlea with intracochlear ECochG during cochlear implantation is feasible, and patterns of response vary by device type. Changes in magnitude alone did not account for hearing preservation rates, but considerations of phase, latency, and neural contribution can help to interpret the changes seen and improve sensitivity and specificity. The correlation between the absolute magnitude obtained either before or during insertion of the ECochG and the hearing threshold changes suggest that cochlear health, which varies by subject, plays an important role.
An accurate TMT-based approach to quantify and model lysine susceptibility to conjugation via N-hydroxysuccinimide esters in a monoclonal antibody

Conjugation of small molecules to proteins through N-hydroxysuccinimide (NHS) esters results in a random distribution of small molecules on lysine residues and the protein N-terminus. While mass spectrometry methods have improved characterization of these protein conjugates, it remains a challenge to quantify the occupancy at individual sites of conjugation. Here, we present a method using Tandem Mass Tags (TMT) that enabled the accurate and sensitive quantification of occupancy at individual conjugation sites in the NIST monoclonal antibody. At conjugation levels relevant to antibody drug conjugates in the clinic, site occupancy data was obtained for 37 individual sites, with average site occupancy data across 2 adjacent lysines obtained for an additional 12 sites. Thus, altogether, a measure of site occupancy was obtained for 98% of the available primary amines. We further showed that removal of the Fc-glycan on the NIST mAb increased conjugation at two specific sites in the heavy chain, demonstrating the utility of this method to identify changes in the susceptibility of individual sites to conjugation. This improved site occupancy data allowed calibration of a bi-parametric linear model for predicting the susceptibility of individual lysines to conjugation from 3D-structure based on their solvent exposures and ionization constants. Trained against the experimental data for lysines from the Fab fragment, the model provided accurate predictions of occupancies at lysine sites from the Fc region and the protein N-terminus (R2 = 0.76). This predictive model will enable improved engineering of antibodies for optimal labeling with fluorophores, toxins, or crosslinkers.
The Gastrointestinal System and Obesity

Abstract The gastrointestinal (GI) system plays a key role in obesity. Obesity is a complex disease in which the excess of adiposity results in increased health risks and disease. The excess of the adiposity is the outcome of a loss of energy balance between food (energy) intake and energy expenditure. Energy intake is mainly regulated by the brain-gut axis. The GI system and its pathophysiology are key players in the regulation of food intake and subsequent progression to obesity. Thus, the GI tract has become the main target for obesity interventions. It is not clear if the GI role in obesity is cause or effect of this disease, and arguments can be made toward both ends. Thus, obesity could be considered a disease of the GI tract, and/or concurrently, obesity is a disease that affects the GI morbidity.
A Stein–Papangelou Goodness-of-Fit Test for Point Processes

Point processes provide a powerful framework for modeling the distribution and interactions of events in time or space. Their flexibility has given rise to a variety of sophisticated models in statistics and machine learning, yet model diagnostic and criticism techniques remain underdeveloped. In this work, we propose a general Stein operator for point processes based on the Papangelou conditional intensity function. We then establish a kernel goodness-of-fit test by defining a Stein discrepancy measure for general point processes. Notably, our test also applies to non-Poisson point processes whose intensity functions contain intractable normalization constants due to the presence of complex interactions among points. We apply our proposed test to several point process models, and show that it outperforms a two-sample test based on the maximum mean discrepancy.
Efficacy and Teaching Mathematics by Telling: A Challenge for Reform.

This paper analyzes the tension between the traditional foundation of efficacy in teaching mathematics and current reform efforts in mathematics education. Drawing substantially on their experiences in learning mathematics, many teachers are disposed to teach mathematics by "telling": by stating facts and demonstrating procedures to their students. Clear and accurate telling provides a foundation for teachers' sense of efficacy--the belief that they can affect student learning--because the direct demonstration of mathematics is taken to be necessary for student learning. A strong sense of efficacy supports teachers' efforts to face difficult challenges and persist in the face of adversity. But current reforms that de-emphasize telling and focus on enabling students' mathematical activity undermine this basis of efficacy. For the current reform to generate deep and lasting changes, teachers must find new foundations for building durable efficacy beliefs that are consistent with reform-based teaching practices. Although productive new "moorings" for efficacy exist, research has not examined how practicing teachers' sense of efficacy shifts as they attempt to align their practice with reform principles. Suggestions for research to chart the development of, and change in, mathematics teachers' sense of efficacy are presented.
Abstract P2-02-07: Targeting iron metabolism in breast cancer: Ferroptosis and genome stability

Iron-sulfur clusters are cell-essential protein cofactors in at least 48 human enzymes supporting diverse cellular functions, including genomic integrity and oxidative phosphorylation, and acting as molecular sensors for oxygen and iron levels. We recently described that breast cancer cells are particularly dependent upon robust iron-sulfur cluster biosynthesis for the survival of elevated oxygen conditions, including seeding lung metastases (1). Moreover, we found that even partially blocking cluster synthesis activated an iron-starvation response, rendering breast cancer cells susceptible to oxidative stress and death by ferroptosis (1). However, the precise mechanisms underlying these phenotypes remain to be fully elucidated. Here, we find that basal-like breast cancer cells are particularly susceptible to suppression of iron-sulfur cluster biosynthesis. By systematically evaluating proteins containing iron-sulfur clusters, we discovered that this susceptibility lies in the intrinsic vulnerability of basal-like breast cancer cells to genomic instability. These results have enabled us to define specific molecular targets in basal-like breast cancer which induce DNA damage, replication fork instability, and apoptosis, with striking subtype specificity. Our findings have broad implications for the underlying differences in genomic integrity in basal-like and luminal breast cancer subsets, and will inform future novel strategies to target genomic integrity in basal-like breast cancer. 1. Alvarez S, Sviderskiy VO, Terzi EM, Papagiannakopoulos T, Moreira AL, Adams S, Sabatini DM, Birsoy K, and Possemato R. NFS1 Undergoes Positive Selection in Lung Tumors and Protects Cells From Elevated Oxygen Levels and Ferroptosis, Nature. 2017 Nov 30;551(7682):639-643. This work was supported by a Susan G. Komen Career Catalyst Award and the NCI (R01 CA214948). Citation Format: Possemato RL, Sviderskiy VO, Alvarez SW, Terzi EM. Targeting iron metabolism in breast cancer: Ferroptosis and genome stability [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-02-07.
Effects of salt-loading on supraoptic vasopressin neurones assessed by ClopHensorN chloride imaging.

Salt-loading (SL) impairs GABAA inhibition of arginine vasopressin (AVP) neurones in the supraoptic nucleus (SON) of the hypothalamus. Based on previous studies, we hypothesised that SL activates tyrosine receptor kinase B (TrkB), down-regulating the activity of K+ /Cl- co-transporter2 (KCC2) and up-regulating Na+ /K+ /Cl- co-transporter1 (NKCC1). These changes in chloride transport would result in increased [Cl- ]i in SON AVP neurones. The study combined virally-mediated chloride imaging with ClopHensorN with a single-cell western blot analysis. An adeno-associated virus with ClopHensorN and a vasopressin promoter (AAV2-0VP1-ClopHensorN) was bilaterally injected in the SON of adult male Sprague-Dawley rats that were either euhydrated (Eu) or salt-loaded (SL) for 7 days. Acutely dissociated SON neurones expressing ClopHensorN were tested for decreases or increases in [Cl- ]i in response to focal application of the GABAA agonist muscimol (100 μmol L-1 ). SON AVP neurones from Eu rats showed muscimol-induced chloride influx (P < 0.05;23/35). SON AVP neurones from SL rats either significantly increased chloride efflux (P < 0.05;27/39) or did not change chloride flux (12/39). The SON AVP neurones that responded to muscimol appeared to be viable and expressed KCC2 and β-actin. Neurones that did not respond during chloride imaging did not show KCC2 and β-actin protein expression. The KCC2 antagonist (VU0240551,10 μmol L-1 ) significantly blocked the chloride influx in cells from Eu rats but did not affect cells from SL rats. A NKCC1 antagonist (bumetanide,10 μmol L-1 ) significantly blocked the chloride efflux in cells from SL rats but had no effect on cells from Eu rats. Blocking NKCC1 using bumetanide had less of an effect on the muscimol-induced Cl- influx in Eu rat neurones compared to the KCC2 antagonist. The TrkB antagonist (AnA-12) (50 μmol L-1 ) and protein kinase inhibitor (K252a) (100 nmol L-1 ) each significantly blocked chloride efflux in SON AVP neurones from SL rats. Salt-loading increases [Cl- ]i in SON AVP neurones via a TrKB-KCC2-NKCC1-dependent mechanism in rats.
Three Strands, One Braid: My Life in Counseling Psychology:

This paper contains the text of the Leona Tyler Award address given by the author in San Francisco in August 2018. The author reviews her career, tracing the three strands that have influenced her ...
Disinfectants Amend the Expression of Membrane Bound Efflux Transporters to Augment Antimicrobial Resistance

Disinfectants are extensively used in health care settings and these active agents demonstrate broad-spectrum antimicrobial activity; however, little is known about their role as inducers/selectors of multidrug resistance in Gram-negative bacteria. To investigate the disinfectant susceptibilities and its role in conferring multidrug resistance in Acinetobacter baumannii, various molecular techniques were performed using standard procedures. The expression of drug specific efflux transporters and non-specific porins were detected by quantitative real time PCR. The susceptibility testing and phenotypic assays demonstrated the role of active efflux in mediating decreased susceptibility to hospital based disinfectants. Interestingly, different disinfectants increased the minimum inhibition concentrations for some of the clinically relevant antibiotics. Additionally, disinfectants also enhanced the expression of drug specific transporters adeB, adeJ, abeM, macB, and non specific transporters that function as porins ompA and carO to augment antimicrobial resistance in A. baumannii. Overall, the study provides experimental evidence highlighting the role of disinfectants as inducers of multidrug resistance in A. baumannii. With such a concern that disinfectant exposure can select for a multidrug resistant population, it is important to implement strict intervention to control and prevent.
ProSPr: Democratized Implementation of Alphafold Protein Distance Prediction Network

Deep neural networks have recently enabled spectacular progress in predicting protein structures, as demonstrated by DeepMind9s winning entry with Alphafold at the latest Critical Assessment of Structure Prediction competition (CASP13). The best protein prediction pipeline leverages intermolecular distance predictions to assemble a final protein model, but this distance prediction network has not been published. Here, we make a trained implementation of this network available to the broader scientific community. We also benchmark its predictive power in the related task of contact prediction against the CASP13 contact prediction winner TripletRes. Access to ProSPr will enable other labs to build on best in class protein distance predictions and to engineer superior protein reconstruction methods.
Debugging the case for creationism

Repeatable artworks like musical works have presented theorists in the ontology of art with a puzzle. They seem in some respects like eternal, immutable objects and in others like created, historical objects. Creationists have embraced the latter appearances and attempted to compel Platonists to follow them. I examine in detail each argument in a cumulative case for Creationism, showing how the Platonist can respond. The conclusion is that the debate between Platonists and Creationists is a stalemate. In order for progress to be made in the first-order debate, second-order progress on the metaontology of art needs to come first.
Design of A Virtual Reality Scenario and Scent Generator for Sensory Training

In the food industry, what makes the difference between a company and its competitors is the quality of its food product, and one of the components that makes quality is the flavor of a product. As trends shift to meet consumer's health and wellness desires formulas are changed with companies trying to retain the same flavoring. This shifting has led to the increased demand of sensory analysis tests. Some of the limitations for sensory analysis is the required space to have the individual booths, time consuming preparation, and material costs. But even with the previous limitations, one of the most important is the training of new users and calibration of existing users. With the development of virtual reality this problem can be more easily rectified by creating a virtual scenario that utilizes all senses and reduces cost of training. The main objective of this research is the development of a virtual scenario for sensory training. This is achieved by recreating a traditional testing environment and training program to analyze scents provided by a scent generator prototype. The methodology will include the design of the training, recreating the environment, programming the interaction with the user and finally the development of a scent generator to release scents.
Chapter 35 – Vaccines

When the body is exposed to a pathogen, the immune system responds to fight the infection. The immune system retains a memory immune response for many years which will provide protection in the event of future encounters with the same pathogen. This phenomenon has been exploited to protect against infection by exposing the body to safe derivatives of the pathogen to induce a protective immune response: these formulations are termed vaccines. An improved understanding of host–pathogen interactions, protective immune responses and novel adjuvants and delivery systems is helping produce safe, effective vaccines against infectious disease. These developments are reviewed in this chapter, along with some of the challenges presented in developing effective, protective vaccines.
Foreword: Western New England Law Review Volume 41

In this Article, the Author reflects on legal education and the role of law reviews. Law reviews not only serve as an educational opportunity, but offer potential legal reforms to help legal scholars, practitioners, and the public understand possible shortcomings of the current state of the law and help law and policy makers contemplate potential improvements.
Retail facility layout considering shopper path

Abstract The physical design of a retail store is known to influence the attitude and behavior of shoppers, in turn affecting the store’s performance. While literature in retail design has alluded to the impact of changes in department placements on impulse revenue, it has not accounted for the resulting changes in shopper path. Changes in shopper path can alter a department’s visibility to shoppers passing by, which could change a department’s impulse revenue. To address this gap, we propose a model for the retail facility layout problem considering shopper path (RFLP-SP) that optimally places departments in the store in order to maximize a retailer’s expected per shopper impulse revenue. Since estimating shopper paths is difficult to express in closed analytical form, we propose a Simulated Annealing based heuristic to generate up to k alternate shortest paths that a shopper may take for a given planned purchase list. This is then embedded in a Particle Swarm Optimization based solution approach to solve the overall RFLP-SP model. Our results suggest up to 13.71% increase in impulse revenue for a deeper store over a square-shaped store, and up to 9.65% increase in one side-door store over other door combinations. Further, the derived solutions are sensitive to shopper basket size, shape of the store, number and location of doors, and adjacency requirement of the departments. We also illustrate the use of our proposed approach on an existing layout of a leading US retailer’s store.
Assessing Hunger Vital Signs in a Pediatric Cardiology Clinic

BACKGROUND and SPECIFIC AIMS: The American Academy of Pediatrics (AAP) notes that food insecurity (FI) at any level increases a child's risk of illness, hospitalizations, behavioral problems, and suffering in school. Growth and development is a major concern in pediatric patients and is a specific concern for pediatric cardiology patients. 1.2 million people living in Allegheny County are food insecure. Based on national data, roughly 42,000 of these individuals are children1, 2. The original Hunger Vital Signs (HVS) asks families two …
Targeting PARP-1 with metronomic therapy modulates MDSC suppressive function and enhances anti-PD-1 immunotherapy in colon cancer.

Background Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) are effective against BRCA-mutated cancers at/near maximum tolerated doses by trapping PARP-1 on damaged chromatin, benefitting only small patient proportions. The benefits of targeting non-DNA repair aspects of PARP with metronomic doses remain unexplored. Methods Colon epithelial cells or mouse or human bone marrow (BM)-derived-myeloid-derived suppressor cells (MDSCs) were stimulated to assess the effect of partial PARP-1 inhibition on inflammatory gene expression or immune suppression. Mice treated with azoxymethane/four dextran-sulfate-sodium cycles or APCMin/+ mice bred into PARP-1+/− or treated with olaparib were used to examine the role of PARP-1 in colitis-induced or spontaneous colon cancer, respectively. Syngeneic MC-38 cell-based (microsatellite instability, MSIhigh) or CT-26 cell-based (microsatellite stable, MSS) tumor models were used to assess the effects of PARP inhibition on host responses and synergy with anti-Programmed cell Death protein (PD)-1 immunotherapy. Results Partial PARP-1 inhibition, via gene heterozygosity or a moderate dose of olaparib, protected against colitis-mediated/APCMin-mediated intestinal tumorigenesis and APCMin-associated cachexia, while extensive inhibition, via gene knockout or a high dose of olaparib, was ineffective or aggravating. A sub-IC50-olaparib dose or PARP-1 heterozygosity was sufficient to block tumorigenesis in a syngeneic colon cancer model by modulating the suppressive function, but not intratumoral migration or differentiation, of MDSCs, with concomitant increases in intratumoral T cell function and cytotoxicity, as assessed by granzyme-B/interferon-γ levels. Adoptive transfer of WT-BM-MDSCs abolished the protective effects of PARP-1 heterozygosity. The mechanism of MDSC modulation involved a reduction in arginase-1/inducible nitric oxide synthase/cyclo-oxygenase-2, but independent of PARP-1 trapping on chromatin. Although a high-concentration olaparib or the high-trapping PARP inhibitor, talazoparib, activated stimulator of interferon gene (STING) in BRCA-proficient cells and induced DNA damage, sub-IC50 concentrations of either drug failed to induce activation of the dsDNA break sensor. STING expression appeared dispensable for MDSC suppressive function and was not strictly required for olaparib-mediated effects. Ironically, STING activation blocked human and mouse MDSC function with no additive effects with olaparib. A metronomic dose of olaparib was highly synergistic with anti-PD-1-based immunotherapy, leading to eradication of MSIhigh or reduction of MSS tumors in mice. Conclusions These results support a paradigm-shifting concept that expands the utility of PARP inhibitor and encourage testing metronomic dosing of PARP inhibitor to enhance the efficacy of checkpoint inhibitor-based immunotherapies in cancer.
Vasoactive intestinal peptide

Abstract Two main candidates have been proposed for the role of relaxant neurotransmitter in the intestine: (a) the purine nucleotide, 5′-adenosine triphosphate (ATP) and (b) the neuropeptide, vasoactive intestinal peptide (VIP). The candidacy of VIP is favored by its precise location in nerve fibers that innervate circular smooth muscle and tenia coli. We have used a photoaffinity analog of ATP, 3′- O -(4-Benzoyl)benzoyl ATP, that binds irreversibly to ATP receptors and inactivates them in the presence of light, and a specific VIP antiserum to examine the claims of VIP and ATP as relaxant neurotransmitters in tenia coli of the guinea pig. Both VIP and ATP caused dose-dependent, tetrodotoxin-insensitive relaxation of tenia coli. The effect of ATP was equipotent to that of its stable isostere α,β-methylene ATP and resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic-P 2 receptors. Photoactivated 3′- O -(4-Benzoyl)benzoyl adenosine triphosphate selectively inhibited relaxation induced by ATP but had no effect on relaxation induced by VIP or by field (i.e., neural) stimulation. Vasoactive intestinal peptide antiserum (final dilution 1:60), on the other hand, inhibited relaxation caused by VIP and by field stimulation but had no effect on relaxation caused by ATP. Neither normal rabbit serum nor preneutralized VIP antiserum had any effect on relaxation induced by ATP, VIP, or field stimulation. Inhibition of neurally induced relaxation by VIP antiserum ranged from 52% ± 7% (p
The Role of Emotional Distress Tolerance on Fear Responding in a Heights-Fearful Sample: Perceived Versus Actual Behavior

Abstract Emotional distress tolerance (EDT)—or the ability to withstand negative emotional states—is considered a transdiagnostic risk factor for psychopathology. Although EDT is theorized to play a role in anxiety development and maintenance, research aiming to delineate the relationship between anxiety and EDT is lacking. The current study tested whether self-reported EDT predicted self-reported and actual avoidance in the presence of feared stimuli using a heights-fearful sample. Moreover, the study tested whether EDT predicted other in-the-moment fear responses, such as peak anxiety, anxious cognitions, and bodily sensations. Participants (N = 128) completed questionnaires assessing fear of heights, negative affect, anxious cognitions, and bodily sensations, as well as two heights behavioral avoidance tasks (BATs). Results demonstrated that EDT did not predict actual avoidance or other in-the-moment fear responses, except for peak anxiety in one BAT. However, EDT predicted self-reported avoidance of heights beyond fear of heights and negative affect. Taken together, results suggest that perception of ability to tolerate emotional distress predicts perception of avoidance of heights, but not actual avoidance of heights or reactions to heights (with the exception of peak anxiety in one BAT). Given these findings, self-reported EDT may not adequately predict how individuals react in anxiety-provoking situations.
Omnidirectional connectivity for the Andean bear (Tremarctos ornatus) across the Colombian Andes

Conserving or restoring connectivity is a common objective of landscape-scale conservation initiatives. However, precise species occurrence or movement data to inform or validate spatial models are often lacking. Our objectives were to (1) produce the first approximation of country-wide connectivity for Andean bears (Tremarctos ornatus) in Colombia and (2) demonstrate a novel approach for model validation which uses publicly available web and social media records of a flagship species. We used general knowledge about Andean bear habitat associations and indices of ecological integrity to construct a resistance surface across the Colombian Andes. We used this resistance surface to model omnidirectional connectivity using circuit theory. We validated our model with coarse location data acquired from local news stories and social media posts. Our model was most sensitive to changes in the resistance values of agricultural landcover and the mid-elevational zone, but uncertainty analysis demonstrated these changes had little impact on our conclusions regarding the municipalities most conducive to Andean bear movement. Just over one-third of those areas most conducive to Andean bear movement were within protected areas, while 8% coincided with agricultural landcover. We constructed a model of connectivity that did not rely on independent, empirically derived location data. Our model is coarse (1 km resolution) but can still provide useful information to practitioners in Colombia who are working with scarce ecological data. More information about how Andean bears move through agricultural landscapes would help improve our understanding of connectivity for this species in Colombia.
Denoising and Inpainting for Point Clouds Compressed by V-PCC

With the development of immersive video, the quality of compressed 3D content has become an important issue. Video-based Point Cloud Compression (V-PCC) is a popular compression method for point cloud sequences; it achieves the highest quality among MPEG proposals. Compressed point clouds suffer from various artifacts when a high quantization parameter (QP) is used. Examining the causes and types of V-PCC artifacts that occur, we propose a framework to remove the highly noticeable outlier and crack artifacts caused by V-PCC so as to improve compressed point cloud visual quality. A subjective experiment showed that our approach provides significantly improved visual quality, and the improvement becomes more obvious with increasing QP values. Objective evaluation with point-to-point Mean Squared Error (p2p-MSE) shows our proposed method can improve point cloud quality and provides competitive results with lower complexity compared with other methods for point cloud outlier removal and inpainting.
Cautionary Tales: Social Representation of Risk in U.S. Newspaper Coverage of Cyberbullying Exemplars

The goal of this mixed-methods study is to investigate how the stories of victims represent the risk of cyberbullying in more than a decade’s worth of U. S. news stories. Exemplars were common, app...
Understanding the Societal Disruption due to COVID-19 via User Tweets

In this paper, we collect data from Twitter and conduct a linguistic analysis of the user tweets to understand the social and economic disruption caused by the COVID-19 pandemic. To better appreciate peoples’ opinions and concerns with regards to the socio-economic conditions of addiction, mental health, unemployment and immigration, we collect data for a period of approximately 3 months in the beginning of the pandemic. We analyze the term and co-occurrence frequencies to identify the most commonly occurring words and bigrams in the discussion for each of the four categories. We conduct semantic role labeling to determine the action words in each category and then adopt a LSTM-based dependency parsing model to identify the main nouns linked with these action words. We then adopt a seeded topic modeling approach to automatically identify the main topics of discussion in each category. We finally conclude with a sentiment analysis of the tweets in each category to determine the overall sentiment associated with each category. Our fine-grained linguistic study unearths the difficulties experienced by the people (e.g., action verb need associated with nouns such as aid and assistance in the unemployment category). We also observe that the overall sentiment in the tweets is negative, driven by people experiencing the pains of job loss, deportation, and the difficulty in accessing programs and treatments related to addiction. Our analysis highlights the main challenges experienced by the people during the start of the COVID-19 crisis and lays the foundation for recognizing and developing the most pertinent public and social policies so as to minimize peoples’ suffering in case of a future pandemic.
The Legal and Regulatory Framework for Thermal Discharge from Nuclear Power Plants

The problem of thermal water pollution as a result of heated cooling water being discharged from nuclear power plants into surface waters is discussed in terms of: the development of regulations for nuclear power plant siting and operation in order to control the effects of thermal pollution; organization of decision-making groups to implement these regulations; historical review of water pollution control laws and programs; the impact of the National Environmental Policy Act (NEPA) of 1970; and miscellaneous environmental bills, laws, and judicial decisions which affect the future of the nuclear power industry. It is concluded that advances in technology, reduction of consumption, and government and corporate responsibility under citizen scrutiny and pressure may eventually bring about a solution to the thermal pollution problem. (LCL)
Queer Legal History: A Field Grows Up and Comes Out

This essay examines recent scholarship on the legal history of sexuality in the United States. It focuses on Margot Canaday's The Straight State: Sexuality and Citizenship in Modern America (2009) and Marc Stein's Sexual Injustice: Supreme Court Decisions from Griswold to Roe (2010). It also reviews recent work on the history of marriage, including Sarah Barringer Gordon's The Spirit of the Law: Religious Voices and the Constitution in Modern America (2010) and George Chauncey's Why Marriage? The History Shaping Today's Debate Over Gay Equality (2004), and the history of military law Defending America: Military Culture and the Cold-War Court Martial (2005), by Elizabeth Lutes Hillman. The essay argues that this scholarship is significant because it offers a different view of sex and power than the one derived from the early writing of Michel Foucault. “Queer legal history” treats the liberalism of the 1960s-1970s as sexually discriminatory as well as liberatory. It underlines the exclusions that were part of public policy under the federal G.I. Bill and the New Deal welfare state.
The Induction of Arginase in Saccharomyces cerevisiae

Saccharomyces cerevisiae can utilize arginine or urea as sole nitrogen source. Arginase degrades arginine to ornithine and urea; urea is catabolized to CO2 and NH3 by the urea degradation system which is composed of a urea carboxylase and an allophanate hydrolase. The arginine analogue, homoarginine, was shown to function as a non-metabolizable inducer of arginase; it is also a competitive inhibitor of this enzyme. Studies on the induction of arginase and of the urea degradation system in a wild type yeast strain grown on minimal medium with ammonia as the nitrogen source have shown that: (a) arginine induces both activities, (b) urea induces only the urea degradation system, (c) homoarginine induces only arginase, and (d) the removal of ammonia, i.e. nitrogen starvation, results in the production of both activities. Starvation of an arginine auxotroph for both arginine and nitrogen does not result in the synthesis of arginase, unless the nonmetabolizable inducer, homoarginine, is added. The urea degradation system is induced by urea but not by arginine in an arginase-negative mutant. Thus, arginase and the urea degradation system appear to be produced independently of each other; the induction of arginase is contingent upon the presence of arginine, while that of the urea degradation system requires the metabolism of this compound to urea.
Tapping into War: Leveraging World War I in the Drive for a Dry Nation

Abstract This study examines the communication efforts of the Anti-Saloon League of America in the years leading up to National Prohibition. The ASLA has been studied in the context of the Progressive Era, but it has not been examined in the context of its role in public relations history even though its efforts, along with those of the suffrage movement, have been said to have contributed to the postwar boom in publicity/public relations firms. Thus, it will be shown that the ASLA employed a multitiered approach in its own fight for a dry nation via national legislation and congressional hearings, its publishing partner, the Scientific Temperance Federation, and its own American Issue. And that it did so by weaving elements of emotion and cognition through messages arising from war-related issues such as anti-German sentiment, patriotism, and rationing. Such an approach might not be so unusual today, nor were elements of its efforts new to advocacy groups at the time, but the League demonstrated that, fo...
Myocardial metabolism and threshold to angina in coronary artery disease after digitalization: Responses at rest and during stress

Abstract To determine the metabolic cost of digitalis to patients with coronary artery disease who were not in congestive heart failure, 15 patients were stressed with atrial pacing before and after the administration of ouabain (0.007 mg/kg). Resting coronary sinus blood flow (118 ± 31 ml/min) and myocardial oxygen consumption (15.8 ± 3.5 ml oxygen/min) increased to 141 ± 25 ml/min (P These findings indicate that digitalization increases myocardial oxygen consumption in nonfailing hearts with coronary artery disease but that this increase is not accompanied by a shift to anaerobic metabolism at rest. Although prior digitalization does not appear to produce additional deleterious metabolic effects during stress, it may sensitize patients to a much earlier awareness of angina.