cssi/SciSciGPT-SciSciNet huggingface dataset:
In situ laminating process for baked starch-based foams.

Abstract Single-use foam packaging made of extruded polystyrene (EPS) or coated paperboard (PB) is used for numerous food and beverage products. Considerable commercial interest is focused in developing new technologies for making single-use food containers that are partially or totally degradable in composting facilities. Wide interest has developed in a baking technology for making starch-based food containers with a hinged lid that appear similar to clamshell containers made of EPS. However, the starch-based food containers are brittle and moisture sensitive and must be coated after baking to provide an adequate moisture barrier. The present study describes an in situ method of baking and laminating the starch-based foams in a single step. The procedure involves a dough formulation consisting of starch, fiber and magnesium stearate that is placed in a mold-heated to 160°C between two sheets of laminate. Sheets of laminate material tested included foil, tissue paper, weighing paper, polyvinyl alcohol film and polyvinyl chloride film. The laminated foams generally had a higher density, tensile strength, elongation to break and flexural strength than the non-laminated sample. All of the laminate materials decreased the water vapor permeance. Foam samples laminated with foil, polyvinyl alcohol (PVOH, processed at 130°C) or polyvinyl chloride sheets had the lowest permeance values and had mechanical properties in the same range as those of commercial containers made of EPS or coated paperboard.
The rationale for local measured service

Abstract This article argues the case for a programme of charging telephone customers for their actual usage of the telephone system. The author compares the telephone to other public utilities and shows the inefficiencies which have arisen from the current flat-rate system. Flat-rate service should be provided as an option for consumers, but only in such a way that low-volume users do not subsidize high-volume users.
An experimental impact oscillator

Abstract The present work considers the impacting behavior of a piecewise linear experimental system, a previous version of which has successfully displayed a wide variety of non-linear, including chaotic, behavior in other previous experiments [1–3]; making use of the ‘ball rolling on a hill’ concept, a cart is constrained to roll along an ‘energy well’ track, shaped in the form of a parabola such that the governing equations of motion of the cart are almost linear. In contrast to previous studies, where the impact condition was fixed (usually at equilibrium), the rigid barrier is placed at varying positions along the track in this study to provide a displacement constraint that gives rise to a discontinuity in the restoring force on the cart (provided solely by gravity in the non-impacting region). Varying the position of the impact can significantly change the overall behavior of the system, and this experimental study will concentrate on behavior where the impact point is varied among three different positions along the parabolic track, one chosen at a position less than equilibrium, one chosen at equilibrium, and one chosen greater than equilibrium; wide and varied responses are observed for these cases. Data were collected with the LabVIEW object-oriented, programmable interface, about which a few salient features are also discussed.
Influence of the 53 kDa glycoprotein on the cooperativity of the Ca2+-ATPase of the sarcoplasmic reticulum

Abstract Previous results from this laboratory suggest that the 53 kDa glycoprotein (GP-53) of rabbit skeletal muscle sarcoplasmic reticulum membrane (SR) may influence coupling between Ca2+ transport and ATP hydrolysis by the Ca2+-ATPase. Here we report evidence that GP-53 may influence the cooperative behavior of the Ca2+-ATPase. The ATPase activity of the Ca2+-ATPase displays negative cooperative dependence (Hill coefficient n 1) on [Ca2+]free. We have determined the degree of cooperativity for native SR vesicles, SR preincubated with antiserum against GP-53 or preimmume serum, and SR partially extracted with KCl-cholate. Our results show that SR preincubated with preimmune serum or SR treated with cholate in 50 mM KCl (yielding membranes rich in GP-53) demonstrate a coperative dependence of Ca2+-ATPase activity on both [ATP] and [Ca2+] similar to that of untreated SR. SR preincubated with anti-GP-53 antiserum (which causes an uncoupling of Ca2+ transport from ATP hydrolysis) or SR extracted with cholate in 1 M KCl (yielding membranes depleted of GP-53) displays decreased positive cooperative dependence on [Ca2+] and decreased negative cooperative dependence on [ATP]. The results are consistent with the interpretation that GP-53 may influence the cooperative behavior of the Ca2+-ATPase.
The Theoretical Biologist's Toolbox: Quantitative Methods for Ecology and Evolutionary Biology

Mathematical modelling is widely used in ecology and evolutionary biology and it is a topic that many biologists find difficult to grasp. In this new textbook Marc Mangel provides a no-nonsense introduction to the skills needed to understand the principles of theoretical and mathematical biology. Fundamental theories and applications are introduced using numerous examples from current biological research, complete with illustrations to highlight key points. Exercises are also included throughout the text to show how theory can be applied and to test knowledge gained so far. Suitable for advanced undergraduate courses in theoretical and mathematical biology, this book forms an essential resource for anyone wanting to gain an understanding of theoretical ecology and evolution.
Parent-Child Communication and Parental Involvement in Latino Adolescents.

This study examines the associations among parent-child relationship characteristics, acculturation and enculturation, and child externalizing symptoms in a sample of 40 Latino parent-adolescent dyads. Specifically, the associations between parent-child relationship characteristics (i.e., communication and parental involvement) and adolescents' externalizing symptoms are examined. Also examined is whether the relationship between these two aspects of the parent-child relationship and adolescent functioning would be moderated by acculturation and enculturation differences between parents and their children. Significant relationships are found among parent-child communication, parental involvement, and child externalizing behaviors; however, neither the acculturation nor enculturation gap moderates these associations.
Real-Time Electrical Characterization of Dielectrophoretic Assembly of Multi-Walled Carbon Nanotubes

This paper reports on a real-time monitoring method for the assembly of a small number of metallic carbon nanotubes (CNTs) by dielectrophoresis (DEP). A time-varying impedance model of the electrode gap was developed to evaluate the number of CNTs which span the gap by measuring the simultaneous variation of gap impedance during the DEP process. Sudden decreases of gap impedance signals were detected during the DEP assembly of multi-walled carbon nanotubes (MWNTs) corresponding to assembly of single or multiple tubes across the gap. The method reduces the requirement of scanning electron microscopy (SEM) inspection and could help automate DEP assembly of CNTs.
The Influence of Regulatory Approach on Tone at the Top

We discuss how the approach taken by regulators to address financial reporting issues has a significant influence on tone at the top. While tone must ultimately be established internally, regulators are more likely to have a positive impact on the quality of financial reporting by addressing organizational tone. A strong tone at the top should ensure that the financial reports are characterized by greater transparency and complete disclosures, and a regulator’s response will depend upon their perspective as to what motivates management. A compliance-based approach, rooted in agency theory’s assumption that managers act in their own best interests, seeks to mandate desirable behavior through elevated monitoring and reduced managerial discretion. Alternatively, an empowerment-based approach rooted in stewardship theory views managers as trustworthy guardians and grants them greater discretion without burdensome external monitoring. In practice, regulations fall on a continuum between these two approaches. To illustrate the continuum between compliance and empowerment, we present three cases in financial and tax reporting and examine the outcomes of these recent regulatory responses. We then provide conclusions regarding the effectiveness of each regulation by considering how tone was influenced within organizations.
Intramolecular dimerization is required for the chlamydia-secreted protease CPAF to degrade host transcriptional factors.

We previously identified a chlamydial protein designated CPAF (chlamydia protease/proteasome-like activity factor) that is secreted into host cell cytosol for degrading host transcription factors required for major histocompatibility complex antigen expression. Here we report that CPAF, synthesized as a 70-kDa proprotein, is processed into two fragments (designated CPAFn and CPAFc) to form intramolecular dimers that are much more stable than the naive CPAF. Precipitation with antibodies that recognized CPAF dimers removed the proteolytic activity responsible for degrading host transcription factor RFX5 from chlamydia-infected host cell cytosol, while precipitation with antibodies that recognized free CPAF fragments alone did not remove this activity. Separation of CPAFn from CPAFc resulted in a loss of proteolytic activity. Furthermore, neither expressed full-length CPAF that was not processed nor coexpressed CPAFn and CPAFc fragments that failed to form dimers degraded RFX5. These observations demonstrate that intramolecular dimerization is required for CPAF to degrade host transcription factors, a strategy that is utilized by an obligate intracellular bacterial species to evade host defenses.
AUV incidents and outcomes

The remote and autonomous underwater vehicle community has been growing at a tremendous rate. The consequence of which is the increased contact of these vehicle systems with the general population who are using the ocean for legitimate business and recreation. Some of these encounters are humorous, some of them are stressful, and others cause us as operators to sigh with great relief that a potential situation didn't occur. The Monterey Bay Aquarium Research Institute (MBARI) has operated remotely operated vehicles for over 20 years. In that time we've had a number of close calls and some closer than we'd like. To date the situations have never given us cause to engage a lawyer but neither have they always been a science success. Currently the majority of the US science community operates without regard to liability, with the possible exception of insurance against an expensive loss. The potential for liability and coverage for damages is a question usually asked after the fact. The purpose of this paper and panel discussion is to consider, with the ocean science users, if a proactive stance regarding potential liability is a pending topic of concern to science. I believe the discussion in this paper demonstrates without a doubt we are facing liability issues and we already have explicit and/or implied requirements to mitigate the potential for detrimental outcomes by our systems operating in the worlds oceans.
It Takes Two to Tango: Monocyte and Macrophage Duality in the Infarcted Heart

Acute myocardial infarction (MI) triggers healing and compensatory responses that serve to restrain damage and maintain cardiac output in the face of myocyte death. These encompass both local events (eg, inflammatory cell infiltration, efferocytosis, myofibroblast transformation, and extracellular matrix turnover) and global events (eg, neurohormonal activation and augmented wall stress) that ultimately result in the generation of a stable infarct scar capable of withstanding distending forces together with variable degrees of left ventricular (LV) enlargement.1–3 The size of the initial infarct and the adequacy of the ensuing wound healing response are both key determinants of the attendant LV dilatation and dysfunction that occur after MI and the subsequent progression to late remodeling and heart failure. In humans, the degree of LV dilatation after MI is the primary determinant of late mortality.4,5 Article, see p 1611 Immune cells are critical for local infarct zone remodeling.3,6–15 Both innate and adaptive immune cell types dynamically infiltrate into the infarct, with the highest activity 1 week after MI, followed by a subsequent decline.10 Following the early appearance of neutrophils, monocytes/macrophages are the predominant cells and display phasic functional heterogeneity that serve to guide proper wound healing. In a seminal report, Swirski et al7 demonstrated that monocytes are rapidly recruited from a splenic reservoir to the infarcted heart where they accumulate and participate in tissue repair. Subsequent studies from these and other investigators8–10 suggested that monocytes/macrophages infiltrate the infarcted heart in 2 phases—an early (≈3–4 days) peak of proinflammatory (Ly6Chi) monocytes and M1 macrophages that promote tissue digestion, followed by a late (≈7–8 days) peak of reparative Ly6Clow monocytes and M2 macrophages that resolve inflammation and promote scar formation and neovascularization—and that proper M1 to M2 macrophage …
Monolysocardiolipin: improved preparation with high yield

A simple, high-yielding preparation of monolysocardiolipin (MLCL) by phospholipase A2 hydrolysis of cardiolipin (CL) in methanol on a semi-preparative scale is described. In methanol, phospholipase A2 preferentially hydrolyzes CL to MLCL. This selectivity results in ∼80% yield of MLCL. The synthesized MLCL and dilysocardiolipin were characterized by NMR and ESI-MS/MS. Only the sn-2 position of CL was hydrolyzed by phospholipase A2 in methanol.
Analytical energy gradients of Coulomb‐attenuated time‐dependent density functional methods for excited states

We present an implementation and validation of the analytical energy gradient of time-dependent density functional theory (TDDFT) using Coulomb-attenuated (CA) functionals for excited state energies, dipole moments, geometries, and vibrational frequencies. The CA-TDDFT gradient is based on the previous long-range corrected TDDFT of (Chiba et al. J Chem Phys 2006, 124, 144106) and the Z-vector formalism of (Furche and Ahlrichs J Chem Phys 2002, 117, 7433). Geometry optimization using CA-TDDFT was carried out for molecules (substituted stilbenes and coumarins) having intramolecular charge-transfer excited states and for a series of small molecules (CO, HCN, CH2O, CH2S, CCl2, C2H2, trans-(CHO)2). We assess the results of the CA functionals, the long-range corrected LC-BLYP functional, and the B3LYP hybrid functional, by comparing to accurate experimental data. The results highlight the applicabilty of different functionals for excited state properties. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Model networks of end-linked polydimethylsiloxane chains. XI. Use of very short network chains to improve ultimate properties

Elastomeric networks were prepared by tetrafunctionally end-linking mixtures of various proportions of relatively long and very short polydimethylsiloxane (PDMS) chains. The former had a number-average molecular weight of 18,500 and the latter either 660 or 220 g mole−1. The series of (unfilled) bimodal networks thus prepared were studied in elongation to the rupture point at 25°C, and in swelling equilibrium in benzene at room temperature. Elasticity constants characterizing the Gaussian regions of the stress–strain isotherms, and values of the degree of equilibrium swelling were used to evaluate the most recent molecular theories of rubberlike elasticity. The isotherms also gave values of the elongation at which the modulus begins to increase anomalously because of limited chain extensibility, and values of the elongation and nominal stress at the point of rupture. These results were interpreted in terms of the known configurational characteristics of the constituent PDMS chains. Values of the energy or work required for rupture were used as an overall measure of the “toughness” of the networks. The very short chains were found to give a marked increase in toughness, through an increase in ultimate strength without the usual corresponding decrease in maximum extensibility. A variety of additional experiments will be required in order to elucidate the molecular origins of this important effect.
Molecular Assays for Targeting Human and Bovine Enteric Viruses in Coastal Waters and Their Application for Library-Independent Source Tracking

Rapid population growth and urban development along waterways and coastal areas have led to decreasing water quality. To examine the effects of upstream anthropogenic activities on microbiological water quality, methods for source-specific testing are required. In this study, molecular assays targeting human enteroviruses (HEV), bovine enteroviruses (BEV), and human adenoviruses (HAdV) were developed and used to identify major sources of fecal contamination in the lower Altamaha River, Georgia. Two-liter grab samples were collected monthly from five tidally influenced stations between July and December 2002. Samples were analyzed by reverse transcription- and nested-PCR. PCR results were confirmed by dot blot hybridization. Eleven and 17 of the 30 surface water samples tested positive for HAdV and HEV, respectively. Two-thirds of the samples tested positive for either HEV or HAdV, and the viruses occurred simultaneously in 26% of samples. BEV were detected in 11 of 30 surface water samples. Binary logistic regression analysis showed that the presence of both human and bovine enteric viruses was not significantly related to either fecal coliform or total coliform levels. The presence of these viruses was directly related to dissolved oxygen and streamflow but inversely related to water temperature, rainfall in the 30 days preceding sampling, and chlorophyll-a concentrations. The stringent host specificity of enteric viruses makes them good library-independent indicators for identification of water pollution sources. Viral pathogen detection by PCR is a highly sensitive and easy-to-use tool for rapid assessment of water quality and fecal contamination when public health risk characterization is not necessary.
Overlapping Functions of ABC Transporters in Topotecan Disposition as Determined in Gene Knockout Mouse Models

It is established that efflux transporters of the ATP-binding cassette (ABC) superfamily can affect the pharmacokinetics of drugs through mechanisms pertaining to drug absorption, elimination, and distribution. To characterize the role of multiple transporters in topotecan's pharmacokinetics, total (lactone+carboxylate) and lactone forms were measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS) in plasma, bile, urine, and feces following intravenous administration at doses of 1 and 4 mg/kg to eight mouse strains: C57BL/6 [wild-type (WT)], Abcb1(-/-), Abcc2(-/-), Abcc4(-/-), Abcg2(-/-), Abcc2;Abcb1(-/-), Abcc2;Abcg2(-/-), and Abcc4;Abcg2(-/-). Compared with WT mice and at both dose levels, the plasma areas under the curve for topotecan lactone were not significantly different in the Abcc2(-/-), Abcc4(-/-), and Abcb1(-/-) strains, whereas significant differences were found in Abcg2(-/-), Abcc2;Abcb1(-/-) (only at the high dose), Abcc4;Abcg2(-/-), and Abcc2;Abcg2(-/-) mice and ranged from 2.1- to 3.3-fold higher. Consistent with these changes, the fecal and biliary excretion of topotecan was reduced, whereas renal elimination was elevated in Abcg2(-/-)-based strains. Similarly, the Abcc2;Abcb1(-/-) strain also had elevated renal elimination and reduced fecal excretion of topotecan lactone. This was more pronounced at the 4 mg/kg dose level, suggesting possible saturation of Abcg2. The Abcc4 transporter was found not to be a major determinant of topotecan pharmacokinetics. It is concluded that Abcg2 has the most significant effect on topotecan elimination, whereas both Abcb1 and Abcc2 have overlapping functions with Abcg2. As such it is relevant to examine how polymorphisms in these transporters influence topotecan activity in patients and whether coadministration of transport modulators could positively affect efficacy without increasing toxicity.
DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses

The endocannabinoid 2-arachidonoylglycerol (2-AG) is biosynthesized by diacylglycerol lipases DAGLα and DAGLβ. Chemical probes to perturb DAGLs are needed to characterize endocannabinoid function in biological processes. Here we report a series of 1,2,3-triazole urea inhibitors, along with paired negative-control and activity-based probes, for the functional analysis of DAGLβ in living systems. Optimized inhibitors showed high selectivity for DAGLβ over other serine hydrolases, including DAGLα (∼60-fold selectivity), and the limited off-targets, such as ABHD6, were also inhibited by the negative-control probe. Using these agents and Daglb(-/-) mice, we show that DAGLβ inactivation lowers 2-AG, as well as arachidonic acid and eicosanoids, in mouse peritoneal macrophages in a manner that is distinct and complementary to disruption of cytosolic phospholipase-A2. We observed a corresponding reduction in lipopolysaccharide-induced tumor necrosis factor-α release. These findings indicate that DAGLβ is a key metabolic hub within a lipid network that regulates proinflammatory responses in macrophages.
Lightning-induced currents in a buried loop conductor and a grounded vertical conductor

Currents in (1) a 100 m by 30 m buried rectangular loop conductor (counterpoise) and (2) a grounded vertical conductor of 7 m height induced by natural and rocket-triggered lightning at distances ranging from 60 to 300 m were recorded in 2005 at the International Center for Lightning Research and Testing (ICLRT). The peak values of 12 triggered lightning channel-base currents and the peak values of the induced currents in the counterpoise are strongly correlated. The first few microseconds of the current induced in the vertical conductor by triggered lightning return strokes 100 m away resemble electric field time derivative waveforms simultaneously measured at the ICLRT. During a close natural lightning flash, five pre-first return stroke current pulses with peak currents up to 140 A were measured in the vertical conductor. These are apparently associated with multiple attempts of an upwarddirected unconnected leader in response to the charge lowered by downward-propagating leader steps.
Effects of Roof Pitch and Gypsum Ceilings on the Behavior of Wood Roof Diaphragms

AbstractTen full-size (3.7×4.9 m) plywood roof diaphragms were constructed using metal-plate-connected (MPC) common and hip wood trusses or joists, typical of single-family dwelling (SFD) construction. The specimens included three gable roof slopes of 33, 67, and 100%, a hip roof of 33% slope, and a flat roof, with a horizontal bottom chord. These roofs were constructed and tested in duplicate to make the total of 10 roofs. Gable and hip roofs were tested with plywood sheathing applied to the eaves, with plywood sheathing removed from the eaves, and with a gypsum ceiling attached to the bottom chord of the trusses. Roofs were tested following standard procedures and analysis. Results showed eave plywood had a negligible effect on diaphragm apparent stiffness; pitch affected gable roof apparent stiffness significantly but did not affect gable roof strength; hip roofs had almost the same apparent stiffness as flat roofs and had the same strength as flat roofs; gable roofs had apparent stiffnesses that were...
The Impact of Enterprise Resource Planning (ERP) Systems on the Audit Report Lag

ABSTRACT: Prior research has shown that the implementation of ERP systems can significantly affect a firm's business operations and processes. However, scant research has been conducted on the relationship between ERP implementation and the timeliness of external audits, such as audit report lags. While some of the alleged benefits of ERP are closely related to removing impediments contributing to audit report lags, others argue that the complex mechanisms of ERP systems create greater complexity for control and audit. In this paper, we examine the relationship between ERP implementations and audit report lags. The test results indicate that overall, a firm's ERP implementation is negatively associated with audit report lag. However, this negative association is significant only at the fourth and fifth years after initial ERP implementation. These results imply that the use of ERP systems by client firms may help decrease the audit report lag, but it takes time for the full impact of the firms' accounting...
Density Functional Theory

Contemporary quantum chemistry presents a quandry. Solution of the Schrodinger equation proceeds to higher and higher accuracy, and molecular properties are computed ever more precisely. But the understanding of molecular properties seems thereby not enhanced. The beauty that is chemistry eludes us.
Constructing Current-Based Gate Models Based on Existing Timing Library

Current-based gate modeling achieves a new level of accuracy in nanoscale design timing and signal integrity analysis. However, to generate current-based gate models requires additional pre-characterization of the gate, e.g., in the form of a new or an extended timing library format. We construct current-based gate models based on the existing Liberty timing library format without further pre-characterization. We present an inverse problem formulation, and propose to solve the problem by quadratic polynomial regression. Our constructed current-based gate models find applications in timing, power, and signal integrity verifications for improved accuracy in library-compatible flows, e.g., to include power supply voltage drop effect in gate delay calculation without further pre-characterization, to calculate gate supply current, etc. Our experimental results show our constructed current-based gate models achieve slightly less accurate results, e.g., within 4.6%(8.6%), than pre-characterized current-based gate models, e.g., within 4.3%(4.4%), of SPICE results in gate delay calculation for ideal (degraded) power supply voltage, and accurate gate supply current calculation.
Carcinoma of the Esophagus: A Disaster

Abstract Because of the extremely high morbidity and mortality associated with esophageal carcinoma and our impression that squamous cell carcinoma of the esophagus was being seen with great frequency in young blacks, a retrospective study was undertaken at Charity Hospital of Louisiana and Touro Infirmary, both in New Orleans, from 1950 to 1965. Of the total of 548 patients studied, 9 survived five years, a rate of 1.6%. This extremely dismal picture was improved in patients who underwent palliative resection, among whom the five-year survival was 6%. Those in whom curative resection was attempted had a five-year survival of 15%. Attention should be paid to nutritional factors in the preoperative period. Preoperative radiation therapy should be considered, and it is suggested that many of these patients would do best with staged procedures involving total thoracic esophagectomy followed by retrosternal colon transplantation.
Longitudinal Trends in Costs of Palliative Radiation for Metastatic Prostate Cancer.

Abstract Background: In recent years, palliative treatment of prostate cancer metastases has been characterized by the use of more complex radiation treatment, despite a lack of evidence demonstrating a clinical benefit of these technologies in the palliative setting. The impact of adoption of these technologies on the costs of palliative radiation treatment in patients with metastatic prostate cancer remains poorly understood in the general patient population. Methods: The study was a retrospective analysis of Surveillance, Epidemiology and End Results (SEER) Medicare data of men aged 66 and older who died from metastatic prostate cancer between 2000 and 2007 and received radiation therapy for bony metastases in the last year of life. Direct costs were obtained from Medicare carrier and outpatient facility payments for all radiation treatment claims and adjusted to 2008 dollars. Results: A total of 1705 men met study inclusion criteria. Total Medicare payments for radiation therapy for bony metastases in...
Genetic Technology and Food Security

In the United States and globally, producers cultivate millions of hectares of genetically modified crops. In the United States, the USDA, EPA, and FDA govern authorization of GMOs under federal laws and agency regulations. Because food produced from GMOs is not considered materially different from conventional food, federal laws require no special labels. To address consumer concerns, states are considering label requirements. Tort remedies are available to redress damage from GMOs, but litigation has not focused on harm from GM food. GM technology is controversial, and many nations have imposed regulatory barriers or prohibitions. In the coming decades, however, GM crops may help to satisfy global demand for food and to meet the challenges of climate change.
Adult respiratory distress syndrome: definition and historical perspective.

The adult respiratory distress syndrome is a reaction of the lung to a variety of severe direct or indirect pulmonary insults. It is characterized by acute respiratory distress, severe hypoxemia requiring high oxygen fractions, and "stiff lungs" requiring approaches to ventilatory management cited elsewhere in this issue of Clinics in Chest Medicine. Increased shunt fraction and dead space ventilation and airless lungs with debris and hyaline membranes are hallmarks of the syndrome, even though the final common pathway, i.e., the mechanism, is not known. The characterization of ARDS creates an important pathological concept for which there is an organized approach to physiologically oriented management. Details of management are cited elsewhere in this issue.
Abstract MS1-2: Targeting CDK 4/6 in breast cancer

For decades, cyclin-dependent kianses (CDKs) have been known to be critical regulators of cell cycle progression leading to the Nobel Prize in 2001 for their identification and characterization. Subsequently, alteration in these and associated proteins have been implicated in cancer. In breast cancer, they have been associated with various molecular subtypes, prognosis, and response to therapy. The concept of blocking CDKs has been around for some time but only recently have they seen clinical success. First generation CDK inhibitors did not demonstrate significant clinical activity and had unacceptable toxicity. In addition to having an appropriate compound, as with other molecular targeted agents, identification of a patient population most likely to benefit is critical to successful clinical development. Palbociclib (PD-0332991, Pfizer) is a first-in-class CDK 4/6 specific inhibitor. Pre-clinical studies identified that ER+ breast cancer models were most sensitive to growth inhibition with palbociclib and identified a synergistic interaction in inhibiting proliferation in combination with anti-estrogens (Finn et al 2009). These data served as a hypotheses for the Phase II Paloma-1/ TRIO 18 study of palbociclib +letrozole vs letrozole alone (Finn et al Lancet Oncolog 2015). Results of this study demonstrated a significant improvement in PFS with the combination and served as the basis for the expedited approval of palbociclib +letrozole as first line therapy for advanced post-menopausal ER+ breast cancer. Most common toxicities were neutropenia, leukopenia and fatigue. Subsequently, a consistent benefit was seen in combination with fulvestrant in more advanced settings (Turner et al NEJM 2015) with a similar toxicity profile. Currently there are several other CDK 4/6 inhibitors in development in breast cancer and other malignancies including abemaciclib (LY2835219, EliLilly) and ribociclib (LEE011, Novartis). In the presentation we will review the rationale for CDK 4/6 inhibition in breast cancer as well as clinical efficacy and toxicity data and the ongoing development of this new class of agent in breast cancer. Citation Format: Finn R. Targeting CDK 4/6 in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr MS1-2.
Involuntary Emotional Expression Disorder

Involuntary emotional expression disorder (IEED), a distressing and potentially debilitating condition characterized by uncontrollable episodes of laughing and/or crying, causes extensive social and occupational dysfunction amongst patients. However, despite affecting more than one million people worldwide, IEED is often overlooked or misdiagnosed, and current treatments are compromised by uncertain efficacy. In this supplement we review the epidemiology and pathophysiology of IEED, and discuss new pharmacologic interventions which may afford opportunities for symptom control amongst IEED sufferers.Although the uncontrollable episodes of emotion which characterize IEED were first described more than a century ago, a bewildering profusion of terminology has since confused and hampered the efforts of physicians to recognize and treat this condition. In the first article, John E. Duda, MD, examines the history of IEED in the medical literature, and evaluates the prevalence of the condition amongst patients in whom emotional or affective motor control has become dysregulated, either as a result of brain damage from neurological disease or as a result of brain injury.
Near infrared photoimmunotherapy of B-cell lymphoma.

Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has successfully treated preclinical tumor models with APCs and is now in the first-in-human phase 1 clinical trial for head and neck cancer patients against EGFR. CD20 is highly expressed in many B-cell lymphomas and is emerging as a molecular target for this disease. Here, we describe the use of the anti-CD20 monoclonal antibody (mAb), rituximab-IR700 APC for NIR-PIT of B-cell lymphoma in two CD20-expressing lymphoma mouse models. CD20 expressing B-cell lymphoma cell lines (Daudi and Ramos) were used in this study. Rituximab-IR700, rituximab conjugated with IRDye700DX, showed specific binding, and cell-specific killing only after exposure of NIR light to both cells in vitro. To evaluate effects of NIR-PIT in vivo, tumor-bearing mice were separated into 4 groups: (1) control; (2) APC i.v. only; (3) NIR light exposure only; (4) APC and NIR light (NIR-PIT). These were performed every week for up to 3 weeks. Rituximab-IR700 showed high tumor accumulation and high target-to-background ratio in vivo. Tumor growth was significantly inhibited by NIR-PIT in comparison with the other groups (p < 0.001 for both tumors), and survival was significantly prolonged in both tumors (p < 0.001 for Daudi tumors and p < 0.0001 for Ramos tumors vs other groups). More than half of tumors were cured with this single regimen of NIR-PIT. In conclusion, anti-CD20 rituximab-IR700 works as a highly effective APC for NIR-PIT against B-cell lymphoma.
Abstract 1232: A-type proanthocyanidins selectively target acute myeloid leukemia cells in vitro and in vivo

Acute myelogenous leukemia (AML) is often a fatal disease where after strong induction therapy most patients relapse and die. A-type proanthocyanidins (A-PACs) are a unique class of compounds found in cranberries (Vaccinium macrocarpon Ait.) that we have found to be effective against several leukemia cell lines and primary AML samples in vitro. Moreover, A-PACs possess a unique ether bond and have ortho-hydroxyl phenolic groups that have the potential to bind to iron, alter redox status, and other biological effects. We found that pre-treatment with antioxidants or holo-transferrin (iron-saturated transferrin) partially protected AML cells from A-PAC induced cell death (p AML-PDX mice (n = 15), were treated for 2.5 weeks via intraperitoneal injections of A-PACs (25 or 50 mg/kg dose every 3 days) or a vehicle control (PBS every 3 days). Mice were sacrificed and leukemia engraftment was evaluated using anti-human CD45 and CD33. Moreover, primary cells treated with A-PACs were assessed for effects on iron metabolism, oxidative stress, cytokine response, and survival pathways by gene expression analysis or flow cytometry. Administration of A-PACs to AML-PDX tumors reduced tumor burden. Mice that were treated with the vehicle control had engraftment of AML primary cells equivalent to 12.51% (95% CI: 4.9, 20.11; n = 5), whereas the mice treated with the 50 mg/kg and 25 mg/kg A-PACs showed a level of engraftment of 5.2% (95% CI: 1.5, 8.9; n = 5) and 5.4% (95% CI: 2.3, 8.5; n = 5), respectively. These results indicated more than a 50% reduction in engraftment, which was better or equal to the effects we observed in mice treated with high-dose cytarabine, a standard care drug. Moreover, no toxic effects were observed in the mice. It was also found that both cells and mice treated with A-PACs lead to the production of specific subset of cytokines. Global gene expression data showed consistent upregulation of some of these cytokines, and also upregulation of NF-κB and enzymes indicative of oxidative stress. The results indicate that A-PACs not only target primary AML cells in vitro, but are also effective in vivo by a potentially novel mechanism. Further elucidation of this mechanism may uncover new vulnerabilities of this disease. Citation Format: Laura M. Bystrom, Luis Andres Lara-Martinez, Bernardo Gomel, Burak Isal, Hongliang Zong, Sabrina Martinez, Catherine Neto, Stefano Rivella, Monica L. Guzman. A-type proanthocyanidins selectively target acute myeloid leukemia cells in vitro and in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1232.
Learning from other people's fear: amygdala-based social reference learning in social anxiety disorder.

Background Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions? Method A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others’ fearful, angry, happy or neutral reactions. Results During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others’ fearful reactions, and a trend towards decreased amygdala activation to objects associated with others’ happy and neutral reactions. Conclusions These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.
Simulating Wildfire Containment with Realistic Tactics

Existing simulation models for fire protection planning rely on a containment algorithm which fails to account for the interaction between the production of containment line and a fire's capacity to spread. This paper describes a technique for simulating wildland fire containment which explicitly accounts for this interaction by extending, generalizing, and, in some cases, simplifying methods reported earlier (Anderson 1983, Albini et al. 1978, Mees 1985, Anderson 1989). Representing the containment boundary in parametric form [i.e., expressing its Cartesian (x, y) or polar (r, O) coordinates as functions of a dimensionless parameter instead of specifying yas a function of xor ras a function of(}], leads to a formalism with two significant advantages: (1) it allows a free choice for the shape of the free burning fire boundary, and (2) it is appropriate for simulations of parallel (indirect) attack as well as direct head and tail attack. In general, the technique requires solution of a first-order, nonlinear, differential equation, a task easily accomplished using numerical methods. The dependence of final fire size and containment time on the line-building rate and eccentricity of the free burning fire boundary are illustrated with the special case of an expanding ellipse and constant linebuilding rate, for which the containment boundary can be obtained by a simple quadrature. Our General Formulation algorithm is demonstrated with a series of simulations that span the range of likely parameters for fire spread and fireline production. Comparisons made on representative fires between predictions of the General Formulation and models currently in use indicate that current models almost always overestimate fire size, sometimes by as much as an order of magnitude. FoR. Scl.42(3):267-281. Additional
Transportation infrastructure asset management in the new millennium: continuing issues, and emerging challenges and opportunities

ABSTRACTThe time has come for renewed emphasis on the life cycle management of the physical aspects of transportation infrastructure. The urgency for this new direction is underscored by the fact that the physical transportation network at most countries constitutes the most valuable publicly owned infrastructure and efforts must be made to keep it resilient to possible threats of man-made or natural disasters over its service life so that the movement of people and goods can continue uninterrupted to serve the economy and maintain the quality of life. The concept of transportation asset management (TAM) is a systematic process based on multiple disciplines (engineering, finance, operations research and economics), to make cost-effective repair and replacement decisions geared towards a sustained state of good repair over the infrastructure life cycle. This paper first argues for the continued application of asset management principles for transportation infrastructure in the new millennium. The paper the...
Ontology- and Sentiment-Aware Review Summarization

In this Web 2.0 era, there is an ever increasing number of product or service reviews, which must be summarized to help consumers effortlessly make informed decisions. Previous work on reviews summarization has simplified the problem by assuming that features (e.g., "display") are independent of each other and that the opinion for each feature in a review is Boolean: positive or negative. However, in reality features may be interrelated – e.g., "display" and "display color" – and the sentiment takes values in a continuous range – e.g., somewhat vs very positive. We present a novel review summarization framework that advances the state-of-the-art by leveraging a domain hierarchy of concepts to handle the semantic overlap among the features, and by accounting for different sentiment levels. We show that the problem is NP-hard and present bounded approximate algorithms to compute the most representative set of sentences, based on a principled opinion coverage framework. We experimentally evaluate the quality of the summaries using both intuitive coverage measure and a user study.
Abstract 108: Thioredoxin-interacting Protein Interacts with Glucose Transporters to Regulate Cardiac Glucose Metabolism

A change in basal glucose transport into skeletal muscle, heart, and adipose is a critical feature of insulin resistance and diabetes. Glucose transport is tightly regulated by a protein family of ...
Biobanking, scientific productions and human rights

Biobanks exist in many forms, sizes, designs and structures. They provide important benefits to humanity. Yet, they also raise serious concerns and complications, especially in the areas of privacy, autonomy and personal data protection. Because these concerns often implicate the rights of individual donors, biobank users, relevant family members and other individual third parties, a logical topic to explore is whether a violation of the rights of these individuals could rise to the level of a human right violation. Commissioned for a book on the legal, ethical and scientific challenges in international biobanking, this chapter provides a brief survey on three distinct sets of human rights issues, all related to biobanks. The first set concerns the human rights involved in the collection, processing, use or storage of the biological materials collected by biobanks. The second set pertains to the human rights issues implicated by the development of scientific productions utilizing the collected materials. The third set relates to the human rights obligations of three types of biobanks: public biobanks, private biobanks and biobanks formed out of public-private partnerships.
Superconvergence of the local discontinuous Galerkin method for the sine-Gordon equation in one space dimension

Abstract In this paper, we present superconvergence results for the local discontinuous Galerkin (LDG) method for the sine-Gordon nonlinear hyperbolic equation in one space dimension. We identify a special numerical flux and a suitable projection of the initial conditions for the LDG scheme for which the L 2 -norm of the LDG solution and its spatial derivative are of order p + 1 , when piecewise polynomials of degree at most p are used. Our numerical experiments demonstrate optimal order of convergence. We further prove superconvergence toward particular projections of the exact solutions. More precisely, we prove that the LDG solution and its spatial derivative are O ( h p + 3 ∕ 2 ) super close to particular projections of the exact solutions, while computational results show higher O ( h p + 2 ) convergence rate. Our analysis is valid for arbitrary regular meshes and for P p polynomials with arbitrary p ≥ 1 . Numerical experiments validating these theoretical results are presented.
Mutation of TGFβ-RII eliminates NSAID cancer chemoprevention.

Non-steroidal anti-inflammatory drugs (NSAIDs) exhibit anti-neoplastic (chemoprevention) activity for sporadic cancers and the hereditary cancer predisposition Lynch syndrome (LS/HNPCC). However, the mechanism of NSAID tumor suppression has remained enigmatic. Defects in the core mismatch repair (MMR) genes MSH2 and MLH1 are the principal drivers of LS/HNPCC. Previous work has demonstrated that the villin-Cre+/-Msh2flox/flox (VpC-Msh2) mouse is a reliable model for LS/HNPCC intestinal tumorigenesis, which is significantly suppressed by treatment with the NSAID aspirin (ASA) similar to human chemoprevention. Here we show that including a TGFβ receptor type-II (Tgfβ-RII) mutation in the VpC-Msh2 mouse (villin-Cre+/-Msh2flox/floxTgfβ-RIIflox/flox ) completely eliminates NSAID tumor suppression. These results provide strong genetic evidence that TGFβ signaling and/or effectors participate in NSAID-dependent anti-neoplastic processes and provide fresh avenues for understanding NSAID chemoprevention and resistance.