cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 2818: An unbiased tumor cell panel profiling method to identify drug-drug interactions reveals synergy between the CDK4 and CDK 6 inhibitor abemaciclib and the Raf dimer and pan-Raf inhibitor LY3009120 in Ras mutant cancers

Drug sensitivity profiling across genomically characterized panels of tumor cells can identify the molecular determinants of drug response. By testing compound combinations in an unbiased format, the same methodology can be used to identify the genomic context of drug-drug synergy. Based on this principle, we developed an unbiased combination screening protocol to identify synergistic interactions with LY3009120, a novel Raf dimer inhibitor that inhibits all three Raf isoforms (Peng et al. 2015, Cancer Cell 28:384-98). Inhibitors of the Ras-MAPK pathway have proven very effective in the treatment of BRAF-mutant melanoma but are, in general, only partially effective in the treatment of BRAF-mutant colorectal cancer and Ras mutant cancers. LY3009120 combined with various compounds was screened across panels of genomically characterized tumor cells. These screens identified a strong synergy with abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4 and CDK6). Statistical analysis of effects in over 500 cancer cell lines showed that mutations in BRAF or Ras family genes were strongly associated with sensitivity to this combination. Strong synergy was observed in skin, colorectal, lung and pancreatic cancers with Ras/Raf mutations, but was also observed in various cancer cells wild type for Ras pathway genes. This included tumor types sensitive to single agent abemaciclib, such as mantle cell lymphoma, ER+ breast cancers, certain leukemias, squamous non-small cell lung cancer, and/or lung cancer with receptor tyrosine kinase activation. In vitro and in vivo analyses of the effects of the combination treatment on signaling pathways in KRAS mutant cancers led to potential mechanistic explanations for the differing efficacy of the combination, which manifests as regression of tumor xenografts in rodent models. Citation Format: Xueqian Gong, Wenjuan Wu, Li-Chun Chio, Susan Pratt, Constance King, Yue Webster, Maria Jose Lallena, Karsten Boehnke, Raquel Torres, Philip Iversen, Christoph Reinhard, Shih-Hsun Chen, Richard Bechmann, Sheng-Bin Peng, Sean Buchanan. An unbiased tumor cell panel profiling method to identify drug-drug interactions reveals synergy between the CDK4 and CDK 6 inhibitor abemaciclib and the Raf dimer and pan-Raf inhibitor LY3009120 in Ras mutant cancers. [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 2818.
How to Catch Capone: The Optimal Punishment of Interrelated Crimes

This paper characterizes optimal criminal punishments when there are multiple interrelated crimes. Optimal punishments are functions of the extent to which related crimes are complements or substitutes weighted by their relative harms to society. The available empirical evidence on the relationship between index crimes in the United States suggests that tailoring criminal punishments properly to incorporate relationships between crimes could reduce the aggregate harm to victims by 3%, or about $8 billion dollars annually, holding enforcement expenditures fixed. The actual harm reduction of a marginal increase in arrests for an index crime is on average about 1.5-3 times greater than the harm reduction calculated without these effects.
Workplace bullying in the foodservice industry

ABSTRACTIn the United States alone, it is estimated that that more than 53.5 million Americans have been victims of bullying at work. As one of the largest private-sector employers in the United States, it stands to reason that the foodservice industry is exceedingly susceptible to this workplace phenomenon. Thus, the purpose of this study was to investigate the presence of workplace bullying behaviors in the foodservice industry. A survey of 440 hospitality workers indicated that foodservice workers witness exclusion, verbal abuse, sexual intimidation, inappropriate jokes, teasing, and mean pranks significantly more frequently than non-foodservice hospitality workers. Practical implications and recommendations for future study are provided.
Radar system design for dual-functionality platforms

Dual-functionality platforms have recently been proposed to jointly and simultaneously enable radar target illumination and establish wireless communication links. This duality serves as means to alleviate the spectrum congestion crisis. In this paper, we consider the problem of radar system design for dual-function radar-communications (DFRC). We develop a new transmit signaling scheme which permits the embedding of communication symbols in the radar signal emissions. The proposed scheme recognizes the radar and communication signal deliveries as the primary and secondary functions, respectively, and strives to have a minimum impact of the DFRC system on radar operation integrity. In particular, we investigate how the embedding of communication symbols into the radar emission affects the transmit power efficiency. The performance of the proposed technique is validated using simulation examples.
Review: King Sigismund Chapel at Cracow Cathedral (1515–1533) by Stanisław Mossakowski

Stanislaw Mossakowski King Sigismund Chapel at Cracow Cathedral (1515–1533) Cracow: IRSA, 2012, 376 pp., 277 b/w and 89 color illus. €120, ISBN 978838983114 The importance of Cracow as a center of Renaissance humanism during the late fifteenth and sixteenth centuries has long been recognized by Anglophone historians and linguists interested in the early modern achievements of scholars at the Jagiellonian University and their contacts with Italian counterparts. Among the more familiar figures are the humanist Filippo Buonaccorsi, called Callimachus (1437–1496), who served as tutor to the sons of King Casimir IV Jagiellon (r. 1447–92), and Nicolaus Copernicus, who studied ancient Greek, mathematics, and astronomy at the Jagiellonian. In spite of Cracow’s renown as a humanist center, there is a paucity of English-language scholarship dedicated to the architecture of Poland-Lithuania, which at its greatest extent, in the early seventeenth century, was the largest state in Europe. This lacuna is in part due to factors such as the linguistic inaccessibility of secondary scholarship written in Polish, as well as geopolitical circumstances between 1939 and 1989. Thus Stanislaw Mossakowski’s erudite monograph King Sigismund Chapel at Cracow Cathedral (1515–1533) , first issued in Polish in 2007, is a significant scholarly achievement. Mossakowski, the well-known and prolific former director of the Institute of Art of the Polish Academy of Sciences in Warsaw, presents here the mausoleum that most clearly embodies some of the earliest Italian Renaissance visual forms to appear in the European borderlands of Poland-Lithuania. The study underlines the relevance of the Sigismund chapel to classically inspired architecture, and by extension to the rich traditions that inform East-Central European architectural history. In nine highly detailed chapters examining the monument’s site, patronage, ideology, and iconography, Mossakowski asserts the uniqueness of the commission and its significance to the broader history of early modern European, and particularly Italian, art and architecture. The centrally planned, elliptically domed monument, located on the south side of the Wawel cathedral nave, decorated and vaulted …
On the ground floor looking up-Managing trainees' uncertainty at the end of life.

Abstract Recent US healthcare policy changes set the stage for integrating palliative and end-of-life care into routine medicine. However, these changes may not affect the daily practice of medical trainees—fellows, residents, and medical students—who as front-line care providers are not always equipped with the skills needed to treat terminally ill patients. We review evidence on trainees' discomfort with end-of-life care and highlight limitations of recent policy changes. Key barriers to proficiency include inadequate conversational training, prognostic uncertainty, and unfamiliarity with hospice and palliative care. Educator-, accreditor-, and policy-level interventions may improve trainees' experience caring for seriously ill patients.
Gene Expression Profiling of Murine HOXB4-Transduced HSCs Shows Multiple Counter-Regulatory Signals That May Control HSC Pool Size

Abstract 2361 HOXB4 is a homeobox transcription factor that can induce hematopoietic stem cell (HSC) expansion both in vivo and in vitro. An interesting feature of HOXB4-induced HSC expansion is that HSC numbers do not exceed normal levels in vivo due to an unexplained physiological capping mechanism. To gain further insight into HOXB4 regulatory signals, we transplanted mice with bone marrow cells that had been transduced with a MSCV-HOXB4-ires-YFP vector and analyzed gene expression profiles in HSC-enriched populations 20 weeks after transplant, a time point at which HSC numbers have expanded to normal levels but no longer increasing beyond physiologic levels. We used Affymetrix arrays to analyze gene expression profiles in bone marrow cells sorted for a Lin − Sca-1 + c-Kit + (LSK), YFP + phenotype. Using ANOVA, we identified1985 probe sets with >2 fold difference in expression (FDR low LSK cells, a highly purified HSC population, obtained from another set of transplanted mice at the 20 week time point. In contrast, other gene expression changes were noted that would potentially limit or decrease stem cell numbers. PRDM16, a set domain transcription factor critical for HSC maintenance and associated with clonal hematopoietic expansions when inadvertently activated as a result of retroviral insertion, was dramatically down-regulated on the expression array and 7.6 fold decreased in the real time PCR assay of CD34 low LSK cells. TFG-beta signaling is a well defined inhibitor HSC proliferation and utilize Smad proteins as downstream effectors. Expression of Smad1 and Smad7 were significantly upregulated on the LSK expression array and 8.1 and 3.5 fold up-regulated by qPCR in CD34 low LSK cells. Another potential counter-regulatory signal was down regulation of Bcl3 mRNA, a potential anti-apoptotic effector in HSCs. We hypothesize that the HOXB4 expansion program involves activation of genes that lead to increased HSC numbers with later activation of counter-regulatory signals that limit expansion to physiologic numbers of HSCs in vivo. We are now examining how this program changes at various time points after transplantation and hypothesize the capping limits are set at relatively later time points during reconstitution. We also are studying the functional effects of these gene expression changes, and in particular, whether enforced expression of HOXB4 and PRMD16 will result in uncontrolled HSC proliferation and/or leukemia. Disclosures: No relevant conflicts of interest to declare.
Use of a Chief Resident Retreat to Develop Key Leadership Skills

Chief residents (CRs) are selected based on interpersonal skills, medical knowledge, and clinical performance; however, they must adapt to their leadership role by taking on administrative tasks, resolving conflicts, and assisting underperforming residents. The Northwestern University McGaw Medical Center identified training area deficiencies and created a one-day curriculum that addressed the role of the CR, conflict resolution and negotiation, managing trainees with clinical/professional deficiencies, supporting trainees in distress, improving program morale, and navigating the Accreditation Council for Graduate Medical Education requirements. A total of 43 CRs participated in the 2016 Leadership Skills Retreat; surveys identified an improvement in reported self-confidence across all content areas.
Glycoprotein Structure and Ulcerative Colitis

Glycoproteins are abundant and markedly heterogeneous constituents of normal colonic mucosa. The large molecular weight mucin glycoproteins predominate and appear to include several distinctive components. Studies using a variety of techniques have indicated that the spectrum of colonic mucin glycoproteins is altered in ulcerative colitis. One class of mucin glycoprotein, species IV, appears to be selectively reduced. In addition, a variety of glycoconjugate determinants recognized by a panel of anti-human colonic mucin glycoproteins has been found to be altered in the colonic mucosa in association with active inflammatory bowel disease. Alterations include the reduced presence of some structures and enhanced expression of others. These findings suggest that inflammatory mediators modulate glycoprotein expression. In addition, isolation of monoclonal antibodies which specifically recognize glycoproteins from patients with ulcerative colitis suggest that distinctive glycoconjugate structures emerge in this disorder. Two monoclonal antibodies, designated MAb UC 7 and UC 11 recognize separate structures which are each specifically found in ulcerative colitis mucosa. Preliminary characterization of the antigenic determinant recognized by one of these antibodies has demonstrated an unusual carbohydrate composition.
Toward a Psychology of Optimal Experience

It is useful to remember occasionally that life unfolds as a chain of subjective experiences. Whatever else life might be, the only evidence we have of it, the only direct data to which we have access, is the succession of events in consciousness. The quality of these experiences determines whether and to what extent life was worth living.
Immunohistochemistry Quality Management and Regulation

Immunohistochemistry testing is highly complex with multiple steps. Assuring the optimum performance of your immunohistochemistry laboratory requires attention to numerous quality monitors. For testing performed on patient specimens, there are also additional regulatory requirements. This chapter answers questions about best practices in quality management in preanalytic, analytic, and postanalytic phases of the total immunohistochemistry test providing examples of possible quality improvement opportunities. It also provides information related to CLIA and FDA regulatory oversight medical devices, in vitro diagnostics (IVD), and analyte-specific reagents (ASR). With regard to immunohistochemistry laboratory accreditation, the final portion of this chapter draws attention to current best practice guidelines of the College of American Pathologists (CAP) relating to immunohistochemistry to prepare for inspection.
The Cardiac Natriuretic Peptide System: Linking the Heart and Kidney in Cardiorenal Homeostasis and Therapeutics

Abstract In 1981, the concept of the heart as an endocrine organ emerged with the discovery of the atrial natriuretic peptide (ANP) by de Bold in 1981. This initial report was followed later by the discovery of B-type natriuretic peptide (BNP) as an additional cardiac hormone which was structurally similar but genetically distinct. It is now established that the precursor prohormones proANP and proBNP are released from the heart in response to atrial stretch and other hemodynamic and inflammatory stimuli. These prohormones are processed to their biologically active forms ANP and BNP, principally by the protease corin, as well as to the biologically inactive NT-proANP and NT-proBNP forms with the kidney and the renin–angiotensin–aldosterone system (RAAS) a principle target. Thus, the cardiac natriuretic peptide (NP) system forms a cardiorenal axis in blood pressure and body fluid homeostasis. Neprilysin (NEP), which is highly expressed in the kidney, is the principal enzyme which degrades the biologically active cardiac natriuretic peptides (ANP and BNP). Importantly, NEP is not involved in the degradation of NT-proANP or NT-proBNP. Biologically active ANP and BNP bind to the same particulate guanylyl cyclase A receptor (pGC-A), activate the second messenger 3′,5′ cyclic guanosine monophosphate (cGMP) and result in pleiotropic actions including natriuresis, vasodilation, suppression of hypertrophy and fibrosis, inhibition of the RAAS, and metabolic protective properties.
Genetic Testing in Endocrinology

In this chapter, we discuss the different factors to consider when evaluating patients with a suspected genetic endocrine disorder so as to guide practitioners through the process of genetic testing and interpretation of results. Clinical examples will be used to highlight the general principles of when and how to use genetic information in the clinical care of patients. Recent advances in our understanding of genetics and genomics are discussed, as well as their implications on the diagnosis and management of rare Mendelian disorders such as multiple endocrine neoplasia type 1, but also multifactorial disorders with a strong genetic component, such as type 2 diabetes mellitus. The reader will hopefully be able to use the information in this chapter as a practical guide on the clinical significance and utility of genetic testing for heritable endocrine disorders.
The Balance Sheet Method at Work: A DSS for the U.S. Coast Guard Fleet Mix Problem

Abstract This paper discusses Fleet Mix, a decision support system (DSS) we have developed for the United States Coast Guard (USCG). It examines the methodology used, the reasoning that led to the methodology, the program itself, the development process, and the technology that allowed the efficient development of this program. We discuss our preliminary findings that 1) the methodology seems sound and is amenable to changes in focus and scope, 2) the program is useful and has been amenable to change, and 3) the development approach used was vital to the success of the program.
Stable Isotope Record of El Niño-Southern Oscillation Events from Easter Island

Easter Island (also known as Rapa Nui and Isla Pascua) lies within the southeastern Pacific high-pressure system, a feature that along with the Indonesian Low comprises the atmospheric dipole that defines the Southern Oscillation. Sea surface temperatures (SST) in the southeastern Pacific influence this limb of the basin-wide Walker circulation by modulating the stability and magnitude of convection within the regionally descending air. El Nino-Southern Oscillation (ENSO) research has most often focused on variability in the intensity and location of the Indonesian Low convective system or on teleconnections to various parts of the Northern Hemisphere. Long climate records from Easter Island will help elucidate the influence of oceanic variability on the overall ENSO system and its South Pacific teleconnections via the Walker Circulation. In addition, the Easter Island region of the South Pacific Gyre is a source for the shallow subsurface meridional flow that eventually upwells along the equator in the central and eastern Pacific [(Fig. 1); Levitus, 1982; Ji, et al., 1995; Gu and Philander, 1997]. In the northern Pacific, subsurface meridional flow has been suggested as a cause of decade-scale climate anomalies (Gu and Philander, 1997; Zhang et al, 1998). A similar mechanism may operate in the Southern Hemisphere; however, our current lack of a long time series of oceanic climate data from the eastern South Pacific Gyre, limits our ability to study this phenomenon.
Alcohol use affects sleep duration among military couples

Alcohol misuse and sleep disorders are highly comorbid, prevalent among service members and their romantic partners, and affected by relationship interdependence. As most military health research f...
Examination of smartphone dependence: Functionally and existentially dependent behavior on the smartphone

Abstract The smartphone, through its small size, ease of use, proliferation of free or cheap apps, and constant connectivity, changes our life in a way that goes well beyond what we experienced with previous media. This study examined smartphone users' perception and evaluation of their dependent behavior during the 2014 communication blackout (March 20) that lasted 6 h in South Korea. Based on the interviews with 70 smartphone users between March 22 and March 30, 2014, this study identified two types of dependence – functional dependence which stresses instrumental usefulness of the smartphone and existential dependence which focuses on obsessed, often unconscious, attachment to the smartphone. Although the two types of dependence may overlap each other, those who perceive existential dependence were more reluctant in acknowledging negative aspects of smartphone use than those who perceive functional dependence. In addition, functionally dependent users were more willing to change their dependent behaviors than existentially dependent people. Smartphone users, regardless of their types of dependence, denied that they were addicted to the smartphone.
Undrained cyclic response of silty sands improved by microbial induced calcium carbonate precipitation

Abstract Loose saturated silty sand can be prone to liquefaction but improving their soil properties is challenging due to their lower permeability compared to clean sands. Microbial induced calcium carbonate precipitation (MICP) is a new, natural and sustainable soil improvement method, which can increase the shear strength and stiffness of soils. In this study, MICP treatment is applied to silty sands with fines content in the range of 0–35% and a constant preshear void ratio 0.7 ± 0.05 to observe improvement in their liquefaction resistance. The specimens are treated until reaching a shear wave velocity about 400 m/s. Cyclic direct simple shear testing is used to evaluate changes in the liquefaction resistance of untreated and MICP treated silty sands. The results show that by applying MICP the liquefaction resistance increases significantly for all fines contents tested, and the treatment efficiency depends on the level of fines content, which dictate the relative density, and the fabric governing the structure. As examples, the 35% fines content specimen has shown the highest improvement, which is related to a higher relative density at this fines content. The silty sand specimens with 5% fines content has a metastable structure which makes the soil more sensitive to cyclic loading. Although the cyclic resistance has increased by applying MICP at this level of fines content, its sensitivity to cyclic loading has remained unchanged. The results of this study demonstrate that MICP improves the cyclic strength of silty sand and can provide an alternative soil improvement method for silty sand.
Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease

Abstract Introduction Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease the striatal vesicular monoamine transporter (VMAT2), secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical cerebral metabolism. Methods PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4–6 months of STN stimulation in seven PD patients (mean age 67 ± 7). Results The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism. Conclusions The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.
An Energy-Efficient Reconfigurable DTLS Cryptographic Engine for Securing Internet-of-Things Applications

This paper presents the first hardware implementation of the datagram transport layer security (DTLS) protocol to enable end-to-end security for the Internet of Things (IoT). A key component of this design is a reconfigurable prime field elliptic curve cryptography (ECC) accelerator that is 238 $\times $ and 9 $\times $ more energy-efficient compared to software and state-of-the-art hardware, respectively. Our full hardware implementation of the DTLS 1.3 protocol provides 438 $\times $ improvement in energy-efficiency over software, along with code size and data memory usage as low as 8 and 3 KB, respectively. The cryptographic accelerators are coupled with an on-chip low-power RISC-V processor to benchmark applications beyond DTLS with up to two orders of magnitude energy savings. The test chip, fabricated in 65-nm CMOS, demonstrates hardware-accelerated DTLS sessions while consuming 44.08 $\mu \text{J}$ /handshake and 0.89 nJ/byte of the encrypted data at 16 MHz and 0.8 V.
Conventional Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome

Pediatric acute respiratory distress syndrome (PARDS) is associated with significant morbidity and mortality. The development of pediatric-specific criteria by the Pediatric Acute Lung Injury Consensus Conference (PALICC) may help with prompt recognition, accurate diagnosis, and prognostication. This may lead to stratification of disease severity to guide therapeutic interventions. The primary objective of conventional ventilation is to achieve effective gas exchange at minimal iatrogenic ventilator-induced lung injury. It is important to emphasize that no mode of ventilation has been demonstrated to be superior in improving outcomes. However, the evolving understanding of ventilation-induced lung injury and respiratory mechanics in ARDS could lead to improvement in techniques to effectively deliver mechanical ventilation. Although PALICC has provided PARDS diagnosis and management recommendations to the pediatric community, it remains up to the investigators to validate the proposed diagnostic criteria and management strategies.
Probability Measure and Characteristic Functional

The variables for the complete description of the statistical properties of turbulence in incompressible Newtonian fluids and the associated equations governing them are set up and their fundamental properties, such as mathematical type, linearity/nonlinearity, solvability, etc., are discussed in the present section.
Accuracy of genomic BLUP when considering a genomic relationship matrix based on the number of the largest eigenvalues: a simulation study

The dimensionality of genomic information is limited by the number of independent chromosome segments (Me), which is a function of the effective population size. This dimensionality can be determined approximately by singular value decomposition of the gene content matrix, by eigenvalue decomposition of the genomic relationship matrix (GRM), or by the number of core animals in the algorithm for proven and young (APY) that maximizes the accuracy of genomic prediction. In the latter, core animals act as proxies to linear combinations of Me. Field studies indicate that a moderate accuracy of genomic selection is achieved with a small dataset, but that further improvement of the accuracy requires much more data. When only one quarter of the optimal number of core animals are used in the APY algorithm, the accuracy of genomic selection is only slightly below the optimal value. This suggests that genomic selection works on clusters of Me. The simulation included datasets with different population sizes and amounts of phenotypic information. Computations were done by genomic best linear unbiased prediction (GBLUP) with selected eigenvalues and corresponding eigenvectors of the GRM set to zero. About four eigenvalues in the GRM explained 10% of the genomic variation, and less than 2% of the total eigenvalues explained 50% of the genomic variation. With limited phenotypic information, the accuracy of GBLUP was close to the peak where most of the smallest eigenvalues were set to zero. With a large amount of phenotypic information, accuracy increased as smaller eigenvalues were added. A small amount of phenotypic data is sufficient to estimate only the effects of the largest eigenvalues and the associated eigenvectors that contain a large fraction of the genomic information, and a very large amount of data is required to estimate the remaining eigenvalues that account for a limited amount of genomic information. Core animals in the APY algorithm act as proxies of almost the same number of eigenvalues. By using an eigenvalues-based approach, it was possible to explain why the moderate accuracy of genomic selection based on small datasets only increases slowly as more data are added.
Generating a Vocabulary of Mourning: Supporting Families Through the Process of Grief:

While grief and loss are common and universal life transitions, the language and customs of grieving differ based on the intersection of family practice and spiritual/religious affiliation. One asp...
Everyday Chaos and the Wisdom of Not Knowing

Like the proverbial iceberg, what is known is “miniscule in relation to what is … unknown…. All of our knowledge rests in a vast sea of not knowing” (Frankel, 2017, p. 3). Life in the early part of...
Evaluating Temperature-Dependent Consumers in a Demand Response Program using Machine Learning

One of the major goals in the European Union for reducing greenhouse gas emissions is the electrification of heat. Therefore, it is expected that the winter peak demand will rise significantly in the next few years. Demand Response could play an important role in reducing the need for network reinforcements by providing flexibility. The major motivation behind this paper is to evaluate the difference in demand flexibility between temperature-dependent consumers using electricity for heating and consumers using other energy sources. In this paper, temperature-dependent consumers are first identified by analyzing their smart metering data with machine learning. Further, the response of consumers is evaluated using probabilistic baseline models. The results show that heat electrification will increase the demand during low temperatures, whereas these consumers will also be able to offer far more flexibility during low temperatures and high demand. To the best of our knowledge, there is no empirical study, that would investigate these using state of the art methods in such detail. The paper presents part of the analyses that were carried out after the real demand response program in the scope of the Slovenian-Japanese NEDO project.
Link between volume, thermal expansion, and bulk metallic glass formability

The specific volumes and thermal expansion coefficients of 41 transition-metal based alloy liquids, which include both bulk and marginal glass-formers, are presented. Those parameters are compared with their values either in the corresponding crystal phases or in their constituent elemental liquids. The volume differences in both cases at the liquidus temperature, ${T}_{l}$, correlate well with the critical thicknesses, ${d}_{\mathrm{crit}}$ of the corresponding glass, taken either from literature or from estimates. The estimates are based on a recent study [Dai et al., J. Non-Cryst. Solids 525, 119673 (2019)], which requires knowledge of the liquid expansion coefficient and viscosity. The volume differences between the better glass-forming liquids and the crystal phases are smaller; they are larger when compared with the elemental liquids. The thermal expansion coefficients of the liquids correlate well with the cohesive energies and fragilities. Their differences with the crystal phases and estimates from elemental liquids correlate well with ${d}_{\mathrm{crit}}$. The differences are smaller for the former and larger for the latter for alloy liquids having larger values of ${d}_{\mathrm{crit}}$. This parameter then appears to be a prime indicator of glass formability. The results are explained in terms of changes in the anharmonicity and structural contributions to the expansion coefficients on alloying.
Unit and regression tests of scientific software: A study on SWMM.

Abstract Testing helps assure software quality by executing a program and uncovering bugs. Scientific software developers often find it challenging to carry out systematic and automated testing due to reasons like inherent model uncertainties and complex floating-point computations. Extending the recent work on analyzing the unit tests written by the developers of the Storm Water Management Model (SWMM) [32] , we report in this paper the investigation of both unit and regression tests of SWMM. The results show that the 2953 unit tests of SWMM have a 39.7% statement-level code coverage and a 82.4% user manual coverage. Meanwhile, an examination of 58 regression tests of SWMM shows a 44.9% statement-level code coverage and a near 100% user manual coverage. We also observe a “getter-setter-getter” testing pattern from the SWMM unit tests, and suggest a diversified way of executing regression tests.
California at war: the state and the people during World War I: by Diane M. T. North, Lawrence, KS, University of Kansas, 2018, 496 pp., $34.95 (hardback), ISBN-13: 978-0-7006-2646-5

This book is an extensively researched and competently written overview of the First World War as experienced by civilians and soldiers from the Golden State. Its format is narrative, with little t...
Computational saturation mutagenesis of SARS-CoV-1 spike glycoprotein: stability, binding affinity, and comparison with SARS-CoV-2

Abstract Severe Acute respiratory syndrome coronavirus (SARS-CoV-1) attaches to the host cell surface to initiate the interaction between the receptor-binding domain (RBD) of its spike glycoprotein (S) and the human Angiotensin-converting enzyme (hACE2) receptor. SARS-CoV-1 mutates frequently because of its RNA genome, which challenges the antiviral development. Here, we performed computational saturation mutagenesis of the S protein of SARS-CoV-1 to identify the residues crucial for its functions. We used the structure-based energy calculations to analyze the effects of the missense mutations on the SARS-CoV-1 S stability and the binding affinity with hACE2. The sequence and structure alignment showed similarities between the S proteins of SARS-CoV-1 and SARS-CoV-2. Interestingly, we found that target mutations of S protein amino acids generate similar effects on their stabilities between SARS-CoV-1 and SARS-CoV-2. For example, G839W of SARS-CoV-1 corresponds to G857W of SARS-CoV-2, which decrease the stability of their S glycoproteins. The viral mutation analysis of the two different SARS-CoV-1 isolates showed that mutations, T487S and L472P, weakened the S-hACE2 binding of the 2003-2004 SARS-CoV-1 isolate. In addition, the mutations of L472P and F360S destabilized the 2003-2004 viral isolate. We further predicted that many mutations on N-linked glycosylation sites would increase the stability of the S glycoprotein. Our results can be of therapeutic importance in the design of antivirals or vaccines against SARS-CoV-1 and SARS-CoV-2. Author Summary Severe acute respiratory syndrome coronavirus (SARS-CoV-1) is an RNA virus that undergoes frequent mutations, which may result in more virulent SARS-CoV-1 variants. To prevent another pandemic in the future, scientists must understand the mechanisms of viral mutations and predict if any variants could become a dominant. The infection of SARS-CoV-1 in cells is largely depending on the interactions of the viral Spike (S) and human angiotensin-converting enzyme 2 (hACE2). We applied a computational method to predict S missense mutations that will make SARS-CoV-1 more virulent. We are interested in the variants that can change SARS-CoV-1 spike protein stability and/or change the virus-receptor interactions. We mutated each residue of SARS-CoV-1 spike to all possible amino acids; we calculated the differences between the folding energy and binding energy of each variant and the wildtype and identified the target S mutations with significant effects on protein stability and protein-protein interaction. We found some viral mutations could destabilize S and weaken S-hACE2 binding of SARS-CoV-1 isolate. Our results show that the computational saturation mutagenesis is a reliable approach in the analysis and prediction of missense mutations.
Taking a History

This chapter addresses all aspects of the medical history: the obstacles, competencies, and recognition of a clinical trajectory from onset to presentation. Obtaining a reliable history requires the collaboration of a bystander or a close family member. Summarizing a medical history for the first time places a tremendous burden, often underappreciated by clinicians. Examples of the value of a good medical history are shown, but also the familiar biases, prejudices, and potential for lost focus and digression when asking questions.
Buckling of Carbon Nanotube-Reinforced Polymer Laminated Composite Materials Subjected to Axial Compression and Shear Loadings

A multi-scale method to predict the stiffness and stability properties of carbon nanotube-reinforced laminates has been developed. This method is used in the prediction of the buckling behavior of laminated carbon nanotube-polyethylene composites formed by stacking layers of carbon nanotube-reinforced polymer with the nanotube alignment axes of each layer oriented in different directions. Linking of intrinsic, nanoscale-material definitions to finite scale-structural properties is achieved via a hierarchical approach in which the elastic properties of the reinforced layers are predicted by an equivalent continuum modeling technique. Solutions for infinitely long symmetrically laminated nanotube-reinforced laminates with simply-supported or clamped edges subjected to axial compression and shear loadings are presented. The study focuses on the influence of nanotube volume fraction, length, orientation, and functionalization on finite-scale laminate response. Results indicate that for the selected laminate configurations considered in this study, angle-ply laminates composed of aligned, non-functionalized carbon nanotube-reinforced lamina exhibit the greatest buckling resistance with 1% nanotube volume fraction of 450 nm uniformly-distributed carbon nanotubes. In addition, hybrid laminates were considered by varying either the volume fraction or nanotube length through-the-thickness of a quasi-isotropic laminate. The ratio of buckling load-to-nanotube weight percent for the hybrid laminates considered indicate the potential for increasing the buckling efficiency of nanotube-reinforced laminates by optimizing nanotube size and proportion with respect to laminate configuration.
Phthiraptera: Chewing and Sucking Lice

Publisher Summary This chapter describes the phthiraptera, an obligatory and lifelong ectoparasites of birds. They are hemimetabolous and wingless, with dorsoventrally flattened bodies, three pairs of well-developed legs, and a single- or double-segmented tarsus usually with one or two claws, but occasionally with claws absent. Ocelli are absent, eyes are reduced or absent, and antennae are short with 3–5 segments. Body length of adults ranges from 0.3 to 12 mm. Over 5000 louse species are recognized. Lice formerly were classified in two orders, Mallophaga (chewing lice) and Anoplura (sucking lice). However, they now are combined into the order Phthiraptera, with the former Mallophaga comprising three suborders (Amblycera, Ischnocera, and Rhynchophthirina) and the Anoplura, a fourth. Although the suborders show substantial differences, they are believed to form a hemipteroid monophyletic unit whose sister group is the Psocoptera (psocids or booklice). Chewing lice have mandibulate mouthparts and probably evolved on birds. They are thought to have fed initially on skin and feathers, with some groups ultimately expanding their diets to include tissue fluids and blood. Some chewing lice eventually made a transition from birds to mammals and some Ricinidae (Amblycera) have mouthparts adapted to pierce host skin.
Combination Vascular Delivery of Herpes Simplex Oncolytic Viruses and Amplicon Mediated Cytokine Gene Transfer Is Effective Therapy for Experimental Liver Cancer

Herpes simplex type I (HSV)-based vectors have been used experimentally for suicide gene therapy, immunomodulatory gene delivery, and direct oncolytic therapy. The current study utilizes the novel concept of regional delivery of an oncolytic virus in combination with or serving as the helper virus for packaging herpes-based amplicon vectors carrying a cytokine transgene, with the goal of identifying if this combination is more efficacious than either modality alone. A replication competent oncolytic HSV (G207) and a replication incompetent HSV amplicon carrying the gene for the immunomodulatory cytokine IL-2 (HSV-IL2) were tested in murine syngeneic colorectal carcinoma and in rat hepatocellular carcinoma models. Liver tumors were treated with vascular delivery of (1) phosphate-buffered saline (PBS), (2) G207, (3) HSV-IL2, (4) G207 and HSV-IL2 mixed in combination (mG207/HSV-IL2), and (5) G207 as the helper virus for packaging the construct HSV-IL2 (pG207/HSV-IL2). Tumor burden was significantly reduced in all treatment groups in both rats and mice treated with highdose G207, HSV-IL2, or both (p < 0.02). When a low dose of virus was used in mice, anti-tumor efficacy was improved by use of G207 and HSV-IL2 in combination or with HSV-IL2 packaged by G207 (p < 0.001). This improvement was abolished when CD4+ and CD8+ lymphocytes were depleted, implying that the enhanced anti-tumor response to low-dose combined therapy is immune mediated. Vascular regional delivery of oncolytic and amplicon HSV vectors can be used to induce improved anti-tumor efficacy by combining oncolytic and immunostimulatory strategies.
In situ activity of a dominant Prochlorococcus ecotype (eHL-II) from rRNA content and cell size.

Summary In the open ocean genetically diverse clades of the unicellular cyanobacteria Prochlorococcus are biogeographically structured along environmental gradients, yet little is known about their in situ activity. To address this gap, here we use the numerically dominant Prochlorococcus clade eHL-II (eMIT9312) as a model organism to develop and apply a method to examine their in situ activity using rRNA content and cell size as metrics of cellular physiology. For two representative isolates (MIT9312 and MIT9215) rRNA cell−1 increases linearly with specific growth rate but is anticorrelated with cell size indicated by flow cytometrically measured (SSC). Although each strain has a unique relationship between cellular rRNA (or cell size) and growth rate, both strains have the same strong positive correlation between rRNA cell−1 SSC−1 and growth rate. We field test this approach and observe distinct patterns of eHL-II clade specific activity (rRNA cell−1 SSC−1) with depth that are consistent with patterns of photosynthetic rates. This molecular technique provides unique insight into the ecology of Prochlorococcus and could potentially be expanded to include other microbes to unravel the ecological and biogeochemical contributions of genetically distinct marine side scatter microbes.
A narrowband interference identification approach for UWB systems

Ultrawideband (UWB) has been attracting attentions by promising very high data rates along with low cost hardware and low power consumption. However, since UWB occupies a very wide frequency band, it is forced to coexist with numerous powerful licensed communication systems transmitting in the same band. The interference caused by these systems may complicate or even block the UWB communications. In the literature, there is considerable amount of work regarding narrowband interference (NBI) suppression. Most of the proposed methods, which can he classified as NBI avoidance and NBI cancellation techniques, require interference statistics. In this paper, we propose an NBI identification approach, which aims at figuring out some useful interference statistics by assuming some preliminary information about the possible sources of NBI
Intentional paradoxes and an inductive theory of propositional quantification

Quantification over propositions is a necessary component of any theory of attitudes capable of providing a semantics of attitude ascriptions and a sophisticated system of reasoning about attitudes. There appear to be two general approaches to propositional quantification. One is developed within a first order quantificational language, the other in the language of higher order logic. The first order theory is described in Asher & Kamp (1986), Asher (1988), Asher and Kamp (1989). This paper concentrates on propositional quantification in a higher order framework, the simple theory of types. I propose a method of resolving difficulties noticed by Prior and Thomason with propositional quantification. The method borrows from Kripke's (1975) definition of truth and results in a partial logic, which I call the simple theory of partial types (SPT). SPT offers a tractable, complete logic (with respect to general models) that includes propositional quantification, accomodates a semantics of the attitudes that avoids logical omniscience, and allows for some self-reference.
A global synthesis of the effects of biological invasions on greenhouse gas emissions.

Aim Evidence is mounting that biological invasions profoundly alter the capacity of ecosystems to regulate or mitigate greenhouse gas (GHG) emissions – a crucial ecosystem service in a changing climate. However, the growing literature has revealed different, even contradictory results and the general pattern over large spatial scales remains obscure. This study synthesizes the effects of invasions by different alien taxa on major GHG emissions. Location Global. Methods A structured meta-analysis of 68 case studies was performed to determine the generality of the effects of biological invasions on emissions of three GHGs and assess the extent to which the heterogeneity of effects can be explained by recipient ecosystems, invasive taxa, functional traits, climate and methodological aspects. Results Invasive alien species increased N2O emissions but promoted carbon sequestration. Effects on CH4 emissions remained inconclusive. Given the general trends, effects differed by ecosystems, with greater N2O emissions in invaded forest and higher increase in carbon stock in invaded grassland. Invasive taxa also mediated the effects of invasions: invasive plants enhanced carbon storage whereas animal invaders consistently showed negative effects. Focusing on exotic plant invasions, N-fixing species caused greater N2O emissions than non-N-fixing species, and for carbon stock, N-fixing and woody plants exerted stronger positive effects than non-N-fixing and herbaceous plants, respectively. Moreover, climatic factors explained the variation in effects of exotic plant invasions but not those of animal invasions. The effects of plant invasions on carbon content varied nonlinearly with climate, with more pronounced effects where temperature and precipitation were extremely high or low. Main conclusions This meta-analysis reveals the overall magnitude and direction of the effects of biological invasions on major GHG emissions, demonstrates that the effects vary substantially by GHGs, biological and environmental factors and proposes avenues for future research. These results highlight the importance of considering species traits and local and climatic conditions in assessing and managing biological invaders.