cssi/SciSciGPT-SciSciNet huggingface dataset:
A Novel Cytotoxic Sequence Contributes to Influenza A Viral Protein PB1-F2 Pathogenicity and Predisposition to Secondary Bacterial Infection

Enhancement of cell death is a distinguishing feature of H1N1 influenza virus A/Puerto Rico/8/34 protein PB1-F2. Comparing the sequences (amino acids [aa] 61 to 87 using PB1-F2 amino acid numbering) of the PB1-F2-derived C-terminal peptides from influenza A viruses inducing high or low levels of cell death, we identified a unique I68, L69, and V70 motif in A/Puerto Rico/8/34 PB1-F2 responsible for promotion of the peptide's cytotoxicity and permeabilization of the mitochondrial membrane. When administered to mice, a 27-mer PB1-F2-derived C-terminal peptide with this amino acid motif caused significantly greater weight loss and pulmonary inflammation than the peptide without it (due to I68T, L69Q, and V70G mutations). Similar to the wild-type peptide, A/Puerto Rico/8/34 elicited significantly higher levels of macrophages, neutrophils, and cytokines in the bronchoalveolar lavage fluid of mice than its mutant counterpart 7 days after infection. Additionally, infection of mice with A/Puerto Rico/8/34 significantly enhanced the levels of morphologically transformed epithelial and immune mononuclear cells recruited in the airways compared with the mutant virus. In the mouse bacterial superinfection model, both peptide and virus with the I68, L69, and V70 sequence accelerated development of pneumococcal pneumonia, as reflected by increased levels of viral and bacterial lung titers and by greater mortality. Here we provide evidence suggesting that the newly identified cytotoxic sequence I68, L69, and V70 of A/Puerto Rico/8/34 PB1-F2 contributes to the pathogenesis of both primary viral and secondary bacterial infections.
Integration of Transforming Growth Factor β and RAS Signaling Silences a RAB5 Guanine Nucleotide Exchange Factor and Enhances Growth Factor-Directed Cell Migration

Transforming growth factor β (TGF-β) receptor (TβR) signaling contributes to normal development as well as tumorigenesis. Here we report that RIN1, a RAB5 guanine nucleotide exchange factor (GEF) and down regulator of receptor tyrosine kinases (RTKs), promotes TβR signaling through enhanced endocytosis. TβR activation induces SNAI1 (Snail), a transcription repressor that reduces RIN1 expression, providing a negative feedback mechanism to control TβR trafficking and downstream signaling. Persistent RAS signaling disrupts this equilibrium by stabilizing SNAI1 protein, resulting in strong silencing of RIN1 and stabilization of RTKs. TGF-β-induced RIN1 silencing in breast cancer cells prolonged sensitivity to hepatocyte growth factor, a ligand for the MET-type RTK, and enhanced growth factor-directed cell motility. We conclude that in some tumor cells TβR and RAS signals are integrated through the silencing of RIN1, leading to a reduction in RAB5-mediated endocytosis. These findings shed new light on the basis for distinct interpretations of TGF-β signaling by normal versus transformed cells.
Remediation of oil-field brine-impacted soil using a subsurface drainage system and hay

This study involved a demonstration of a novel remediation technology for brine-impacted soil at a site in Osage County, Oklahoma, which was recently contaminated with produced-water brine from a leak in a steel line leading to a saltwater disposal well. At this site, topsoil was underlain by clay-rich subsoil, which had resulted in leaching and transport of brine components from the site to an environmental receptor (farm pond) downgradient. Encouraging further movement of brine components using natural drainage patterns would have only further contaminated the pond. A subsurface drainage system was installed to intercept brine components, enhance the lateral subsurface transport process, and prevent further contamination of the pond. Chloride and sodium concentrations in the soil were reduced by an average of 93 and 78%, respectively, in the 4 yr after the subsurface drainage system was installed. More importantly, approximately 95% of the site revegetated during this period. This is in stark contrast to the complete lack of vegetation before the current work was initiated. A thick layer of prairie hay was applied across the surface of this site after the subsurface drainage system was installed. In addition to limiting the rate of evaporation from the site, this organic material appears to have also been a significant factor in desalination and revegetation of the site. The fibrous hay enhanced leaching after mechanical disruption of the soil and provided soil organic matter that helped to build soil structure and sustain the soil ecosystem. Based on the results from this study, a two-step remediation strategy for brine-impacted topsoil is proposed. The first step involves the tilling of hay and fertilizer into the soil, whereas the second step involves a subsurface drainage system, if necessary.
The Pragmatic Values of Evidential Sentences

Lewis (1976, 1986b) concentrates on material conditionals, arguing that their semantic values are propositional but that their pragmatic values are given by conditional subjective probabilities. Thus, from the start, the general theses (1) were linked to close linguistic analysis involving both semantic and pragmatic considerations. One comes away from Lewis’s papers with the sense that they could form the cornerstone for a successful (probabilistic) formal pragmatic theory. The present paper investigates the pragmatics of evidential sentences in the general Lewisian terms (1). Now, evidential morphemes are rich and varied in their contributions, they might not form a natural class cross-linguistically (Matthewson et al. 2007:3, Speas 2007), and analyzing even a single morpheme generally proves complex (Davis et al. 2007, Fasola 2007). Thus, we do not, in this short paper, venture a comprehensive analysis. Rather, we focus on the pragmatic strategy that evidentials facilitate. Section 2 discusses the pragmatics of evidentiality. Section 3 carves out a role for probabilities in pragmatic theory, and Section 4 describes our analysis. We close the paper with a discussion of the connections between evidentiality and modality (Section 5) and a brief look at various promising extensions of these ideas (Section 6).
High-sensitivity 40-gb/s RZ-DPSK with forward error correction

A high-sensitivity 40-Gb/s differential-phase-shift-keyed (DPSK) system with coding is demonstrated with back-to-back sensitivity as good as 8.7 photons per bit at a 10/sup -9/ bit-error rate. Coding is done on the 40-Gb/s data using high-speed electrical multiplexers and demultiplexers combined with four 10-Gb/s forward error correction chips that operate with 7% overhead. The DPSK receiver uses a simple approach to DPSK balanced detection.
Application of an Urban Fire Simulation Model

Computer models that simulate post-earthquake urban fires can be useful for improving understanding of the phenomenon, estimating risk, evaluating the relative effectiveness of possible risk reduct...
Assortative mating in captive cowbirds is predicted by social experience

Experimental evidence has shown that brown-headed cowbirds, Molothrus ater, display pairing preferences for their native population. Here, the question of whether social experience affects such preferences was tested. Four groups of juvenile female and male cowbirds from a South Dakota population were housed either with adult birds from the same population or with adult birds from an Indiana population. The Indiana population is from a different subspecies from the South Dakota population, and adult Indiana cowbirds display communicative behaviours that are differe nt from adult South Dakota cowbirds; the communicative cultures of the two populations thus are distinct. The pairing and mating patterns of the juvenile females and males were assessed during their first two breeding seasons. In the first year, 71.4% of the pairings that occurred in a testing aviary were between unfamiliar birds of the same cultural background. In the second year of testing, after another winter of social experience with adults of their respective cultures, 86.2% of the pairings, and 77.3% of the copulations, that occurred were between birds of the same cultural background. These data demon­ strate the learning of population-speci fic courtship and mating patterns in cowbirds, and are amon g the strongest experimental data to date indicating assortative mating in birds based upon social experience.
Ip-norm optimum filters for image recognition. Part II: performance evaluation

We examined the performance of linear and nonlinear processors (filters) for image recognition that are lp-norm optimum in terms of tolerance to input noise and discrimination capabilities. These processors were developed by minimizing the lp norm of the filter output due to the input scene and the output due to the noise. We tested the performance of the lp-norm optimum filters by measuring the average peak-to-sidelobe ratio of the output of the filters for different values of p. We also tested the performance of these filters by placing a target in a scene containing additive noise and a realistic background. For the images presented here, the filters detected the target in the presence of additive noise and a realistic background. The tests conducted show that the discrimination capabilities of the lp-norm filters improve as p decreases (p>1). This is shown by sharper peaks at the target location and higher average peak-to-sidelobe ratios for smaller values of p.
Federalism, Efficiency, and Civil Rights Enforcement

This article systematically compares the efficiency of federal, state, and local civil rights agencies in enforcing national fair housing policy over time, with special attention to the South. State and local agencies processed Fair Housing Act complaints more efficiently than the U.S. Department of Housing and Urban Development (HUD), southern agencies outperformed HUD, and the probability that a racial discrimination complaint resulted in a favorable outcome for the alleged victim was the same for complaints originating within and outside the South. These findings suggest that the fair housing enforcement model may provide useful concepts for sharing power in other policy areas in the American federal system.
Sex Differences in the Effects of Alcohol and Other Psychoactive Drugs on Endocrine Function Clinical and Experimental Evidence

There is relatively little information on the effects of psychoactive drugs on neuroendocrine function in humans or animals of either sex. In this brief narrative, those data that are available are reviewed. As is evident, in some areas there are few or no data on the effects of psychoactive drugs on neuroendocrine function in the female, providing little basis for a review of male—female differences in neuroendocrine responses to psychoactive drugs. Nevertheless, it is hoped a state-of-the-art analysis of the male will provide a firm basis for badly needed future studies of the female.
Electoral Institutions and Political Competition: Coordination, Persuasion and Mobilization

In the Schumpeterian conception, democracy consists of regular and non-violent competition for control of government between alternative teams of elites (Schumpeter 1942). The question that much scholarship in electoral studies addresses, and on which this essay will focus, is: how does changing the rules of the electoral game change the strategies of parties and candidates, hence the outcome of elections? Figure 1 illustrates both the sequence of events in a stylized democracy and some of the topics to be covered. In the beginning, there is a set of potential electoral competitors. These agents decide (at stage 1 of the diagram) whether to enter a particular electoral competition—that is, to formally nominate candidates for one or more elective offices. Since winning office requires amassing a sufficient number of votes, the nature of the entry game between potential competitors has a strong coordination game flavor to it.1 For example, if fifteen right-of-center parties all enter the race as separate competitors, while the left unites behind a single option, the right is likely to do poorly (under most extant electoral systems). The right can do better if some potential competitors withdraw in favor of others, but each potential competitor may prefer that it remain and the others withdraw. After a given set of competitors have entered the race, each decides to allocate effort to one or more of three vote-producing activities: (2.1) persuasion: providing voters with reasons, such as better policy positions or larger bribes, to prefer it to the other competitors; (2.2) vote coordination: convincing supporters of other parties that the expected utility of their vote, in terms of affecting the allocation of seats across competitors, will be higher if they support it than if they support their most-preferred competitor; (2.3) mobilization: boosting the probability that its known supporters will actually participate in the election.
Values in the Law

The aim of this book is to fill a gap between general jurisprudential theories applicable to all legal systems and detailed analyses of particular fields of law. We have developed normative principles for common-law fields that would be acceptable to rational persons. At this point one might find the number of principles and topics discussed blocking any overall view. Consequently, we should step back and briefly review certain themes running through the more detailed analyses.
Brief paper: Adaptive input matching control of structurally varying plants

Adaptive control using input matching can avoid the identifiability and/or exact model-matching constraints of the bulk of existing adaptive control methods. The focus on input matchability allows the use of general controller structures capable of controlling a plant whose structure may vary arbitrarily within an allowable class. The applicability of this technique is demonstrated for two simulated plants: a MIMO linear network increasing its complexity due to component failure and an unstable SISO plant controlled by an actuator which gradually develops a nonlinearity. The sole need for pre-specification of an allowable plant structure re-focuses the thrust of system identification from parameter estimation to structure determination.
The Fair Trade Experiment in California: Edna Gleason and the Druggists' Campaign, 1929-1933

An unlikely leader in the California fair trade movement, Edna Gleason, known as the “Mother of Fair Trade,” exemplified the dual appeal of woman as citizen-consumer and businessperson as protector of the public interest. A self-taught pharmacist and entrepreneur, Gleason spearheaded first local, then regional, and finally national efforts to protect retail proprietors from aggressive price-cutting by corporate competitors. For Gleason and her fellow trade association members, fair trade entailed association management of trade practices, including service guarantees, quality controls, cost accounting methods, and price scheduling between manufacturer and retailer. She spearheaded the California campaign for fair trade legislation that exempted proprietors from antitrust prosecution when contractually seeking these goals. Their objective was to compete on grounds other than price during a time of extreme price deflation, reflate retail prices, and thereby save proprietors and laborers from business closures. Gleason’s story underscores a venue in which women had long been effective – state and local government. The fair trade movement, which began at this level, ultimately, exercised a decisive influence on the national political economy. As California fair trade succeeded in protecting proprietary capitalists and stabilizing retail prices in the drug industry, similar goals pursued by the National Recovery Administration were axed by the Supreme Court, making room for new legislation to stabilize the economy. Gleason traveled to Washington and with the National Association of Retail Druggists and the American Fair Trade League campaigned for national fair trade legislation, which they won with the Miller-Tydings Act of 1937. While the conventional history of trade association regulation dismisses these efforts as rent-seeking or doomed to collective action failure, this paper recovers an alternative vision of American capitalism that did indeed influence corporate behavior and helped create markets for quality-controlled and cooperatively regulated therapeutics.
Residual Stresses in Austenitic Generator End-Rings

The rings which retain the end windings of large electrical generators are manufactured from highly alloyed austenitic steels. To reach the strength levels required to withstand the centifugal stresses experienced during operation the end-rings are produced in the work hardened condition, achieved using a cold expansion process. Residual stresses have been examined in end-rings using a combination of techniques. Centre-hole stress measurements have been made on machined surfaces using the air abrasive drilling method. X-ray diffraction techniques have also been utilised together with incremental electropolishing to allow the determination of the steep stress gradients characteristic of machining operations. The investigations include machining trials performed on a full size component and on workshop specimens with systematic variation of the cutting parameters. The complexity of the stress fields is discussed.
Safety and feasibility of focused ultrasound neuromodulation in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common pharmacologically refractory form of epilepsy. While it can often be effectively treated by temporal lobe surgery, that does not always eliminate seizures, and many patients are not suitable candidates for surgery. A non-invasive method to augment surgical or medical treatment of TLE would be highly useful. Low-intensity focused ultrasound pulsation (LIFUP) offers the potential for non-invasive neuromodulation, and in animal studies has not shown any evidence of tissue damage. However, the technology has not yet been tested in humans. We are currently testing the safety and feasibility of using a LIFUP device on humans to modulate brain activity in the temporal lobe.
Biodegradable Plastics Derived from Cellulose and Chitosan

Recently environment pollution caused by waste plastics has become a global problem. One of the countermeasure has been directed to biodegradable plastics that are decomposed within soils, and some biodegradable plastics have been proposed. Natural polymers such as cellulose are decomposed with microorganisms in soil and the decomposed materials will not pollute the environment. Judging from the capability to be decomposed, natural polymers, which exist in nature abundantly, should be excellent biodegradable plastics materials. In this regard, we have developed new biodegradable plastics by making natural polymers into composites. The materials are finely divided cellulose and chitosan that is produced by deacetylation of chitin. Here, the novel biodegradable plastics developed by us and their applications are reported.Cellulose, when suspended with water, becomes anionic in the surface by actions of hydroxy group and a trace amount of carboxyl group in cellulose. On the other hand, while chitosan is insoluble in water, its salts such as with acetic acid become water-soluble and cationic. Chitosan has good affinity with cellulose because of the similarity in structure. Taking advantage of these characteristics, we have developed high performance papers and biodegradable plastics.Cellulose-chitosan composite film demonstrate higher strength than general purpose plastic films, and wet strength peak when chitosan content is 10-20%. The relatively small amount of chitosan needed is economically convenient because chitosan is more expensive than cellulose. This film biodegrade well in soil, completely dissolving and disappearing in two months. Biodegradability is influenced by the temperature used in thermal treatment the film, the quantity of acid groups in the cellulose, and other factors. These characteristics will be used to control decomposition. Since cellulose-chitosan plastics are not thermo-plastics, we have been working on joint research with companies to produce films, nonwoven fabrics and foams. We discuss here the properties and application of these composite moldings.
Effects of enkephalin expressing from pEGFP-C3-PENK/NIH3T3 cells on PKA expression of nerve cells

Aim:To observe the inhibition of excitability of nerve cell pain model by enkephalin expressing from pEGFP-C3-PENK/NIH3T3 cells.Methods:The neonatal rat cortical neurons were cultured.Planted neurons were cultured in plates of 106 mL-1 density,then divided into four groups:control group,prostaglandin(PG) stimulation group,PG stimulation plus enkephalin group,and naloxone antagonist group.Neuron cells were collected after 24 h,total protein was extracted,and the amount of phosphor-protein kinase A(PKA) of each group of neurons was detected by Western blot method.Results:There were significant differences among four groups in PKA content(F=59.873,P0.001).Compared with control group,PKA content increased in PG stimulation group(P0.05).Compared with PG stimulation group,PKA content reduced in PG stimulation plus enkephalin group(P0.05).Compared with PG stimulation plus enkephalin group,PKA content increased in naloxone antagonist group(P0.05).Conclusion:Enkephalin expressed by pEGFP-C3-PENK/NIH3T3 cells could inhibit activation of PKA system of nerve cells,and the effect could be antagonisted by naloxone.
Epidemiology of public health emergencies in Hubei province,2004-2013

Objective To understand the epidemiological characteristics of public health emergencies in Hubei province from 2004 to 2013. Methods Descriptive epidemiological analysis w as conducted on the reported incidence data of public health emergencies in Hubei province during this period. Results A total of 910 public health emergencies w ere reported,in w hich 2( 2. 2%) w ere classified as grade Ⅱ events,78( 8. 57%) w ere classified as grade Ⅲ events and830( 91. 21%) w ere classified as grade Ⅳ events. Poisoning accounted for 79. 49% of grade Ⅲ public health emergencies. Up to 791 public health emergencies w ere communicable disease outbreaks,accounting for 86. 92%. The case fatality rate of heat stroke w as highest( 100%),follow ed by that of poisoning( 4. 29%). The annual incidence peaks w ere during M arch-June and during September-November,the public health emergencies occurred during these tw o periods accounted for 78. 92% of the total. A total of 717 public health emergencies occurred in schools( 78. 79%).The numbers of reported public health emergencies varied w ith area. Conclusion It is essential to strengthen the prevention and control of communicable diseases in schools to reduce the incidence of public health emergencies and it is important to strengthen the health education to reduce the incidence of poisoning.
Testing the clean room of Medical Instrument Production Enterprise

this paper mainly introduced the standards,methods and attentions concerned with the environment monitoring of medical instrument production enterprise,as well as some troubles met within the test progress.
Comparison of Common Immunoassay Kits for Effective Application in Workplace Drug Urinalysis.

Workplace drug urinalysis protocols include an initial immunoassay followed by a confirmation gas chromatography/mass spectrometry (GC/MS) test of immunoassay-positive samples. (Drug categories that are commonly tested include: amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, lysergic acid diethyl amide, methadone, methaqualone, opiates, phencyclidine, and propoxyphene. Not all drug categories are tested by all workplace drug urinalysis programs.) Only those samples that are tested positive by both the initial and the confirmatory procedures can be reported as positive. Thus, when adopting an immunoassay, one must have knowledge of the assay's cross-reacting characteristics and the assay's apparent analyze concentration that corresponds to a specific analyze concentration determined by the GC/MS procedure. The underlying principles of the commonly used radioimmunoassay, enzyme immunoassay, fluorescence polarization immunoassay, and particle immunoassay are outlined. Cross-reacting characteristics of these immunoassays as reported by the manufacturers and independent laboratories are tabulated. This information shown that commercial immunoassay kits for drug categories that are included in workplace drug urinalysis programs are generally more specific than those kits that are for clinical use only. Furthermore, recently manufactured immunoassay kits targeted for use in workplace drug urinalysis programs are more specific than those manufactured earlier. Reported effects of adulterants, such as salt, cleaning agents, etc., on commonly used immunoassays are summarized. Without more comprehensive and systematic studies, it is difficult to make general statements concerning the superiority of one methodology over the others. It is clear, however, that cannabinoid assesses are most susceptible to the influence of adulterants. Reported immunoassay-GC/MS correlation data are reviewed. Significant correlations exist in all cases. The immunoassay apparent analyze concentration corresponding to a specific GC/MS analyze concentration may be approximately based on the resulting regression equations. Since the corresponding immunoassay apparent analyze concentrations vary with the specificities of the reagent used, the immunoassay reagent manufacturers should carefully study specificity characteristics of each manufacturing batch and provide these correlation data for users' evaluation and adaptation.
Evaluation of a Proposed Reconditioning Process for Frozen Shrimp

A proposed procedure for reconditioning filth-contaminated shrimp was evaluated for its effectiveness in removing urea, a component of soluble filth. Contamination of fresh shrimp was simulated by placing 1.0 μl aliquots of a solution containing 0.025 × 10-6mCi 14C-urea onto the epithelium of peeled shrimp. Following the washing procedure, 41% of the labeled urea remained with the shrimp tissue.
The Effect of Course Time Compression on Academic Performance in Construction Surveying

The goal of this study was to explore the differences in academic performance between students who took the full 16-week fall-spring semester courses and students that took the compressed 10-day mini-mester course in construction surveying. There were no instructional design differences between semester courses with respect to instructor, contact hours, instructional design, delivery method, materials, activities, applications, quizzes, exams or grading. This study found that students taking the compressed mini-mester course had significantly better achievement on the laboratory activities and the reading quizzes than that of the students taking the full-semester courses. However, the students taking the full-semester courses significantly exhibit better achievement on the two course exams than did the students taking the compressed mini-mester course. No significant difference was found on total course points. Student undergraduate Grade Point Average (GPA), Scholastic Aptitude Test (SAT) and Tes...
Route to One Atomic Unit of Time: Development of a Broadband Attosecond Streak Camera

A new attosecond streak camera based on a three-meter-long magnetic-bottle time-of-flight electron spectrometer (MBES) is developed. The temporal resolution of the photoelectron detection system is measured to be better than 250 ps, which is sufficient to achieve an energy resolution of 0.5 eV at 150 eV photoelectron energy. In preliminary experiments, a 94-as isolated XUV pulse was generated and characterized. With a new algorithm to retrieve the amplitude and phase of XUV pulses (PROOF—phase retrieval by omega oscillation filtering), the attosecond streak camera will be able to characterize isolated attosecond pulses as short as one atomic unit of time (25 as).
The Method of Multipliers for Inequality Constrained and Nondifferentiable Optimization Problems

This chapter discusses the method of multipliers for inequality constrained and nondifferentiable optimization problems. It presents one-sided and two-sided inequality constraints. It is possible to convert nonlinear programming problem (NLP) into an equality constrained problem by introducing a vector of additional variables. An efficient approach is presented that requires only one multiplier per two-sided constraint. The chapter presents approximation procedures for non-differentiable and III-conditioned optimization problems.
Neoliberal Masculinities in Contemporary Peruvian Cinema: Octubre and El Limpiador

The record economic growth during the last decade known as the “Peruvian Miracle” could be interpreted as the pinnacle of the neoliberal reform program implemented by president Alberto Fujimori in the 1990s. Despite Peru’s sudden economic bonanza and the expansion of its middle class, this transformation has simultaneously had a damaging impact on daily lives, marginal sectors and traditional practices. In this chapter, Diaz-Zambrana argues that the wounded male image in the films Octubre (Daniel Vega and Diego Vega, 2010) and El limpiador (Adrian Saba, 2013) depicts a symptomatic citizen whose inability to develop solidary bonds and relate to historical/cultural memory are direct consequences of the market-based society and its debilitating effect on morality, affects and history. Thus, the corrosive effect that neoliberal imperatives impose on social interactions, past traumas and cultural rituals will be displayed in both cinematic narratives through conflicted and emotionally detached male figures and the dystopic representation of urban spaces and relations.
Transnational Governance and Peace Processes: The Case of the UN and ICC in Colombia

International institutions provide a structure for cooperation among states, but they also insert themselves into national and local political spaces, as conveyors and propagators of international norms in domestic spaces, “third-side” providers of good offices brokering between governments and society, and providers of resources to help address problems. The UN and the ICC played a direct role in influencing the process and outcomes of political responses to the conflict in Colombia. The UNHCR and UNDP shaped the treatment of victims, targeting of funding, and the political incentives for peace. The ICC pushed negotiators to incorporate international transitional justice norms embodied in the Rome Statute against impunity. This chapter traces the mechanisms through which these international institutions have penetrated domestic political spaces for peace in Colombia.
The Role of Inhibition of Apoptosis in Acute Leukemias and Myelodysplastic Syndrome

Avoidance of apoptosis is a key mechanism that malignancies, including acute leukemias and MDS, utilize in order to proliferate and resist chemotherapy. Recently, venetoclax, an inhibitor of the anti-apoptotic protein BCL-2, has been approved for the treatment of upfront AML in an unfit, elderly population. This paper reviews the pre-clinical and clinical data for apoptosis inhibitors currently in development for the treatment of AML, ALL, and MDS.
Unbiased screen of RNA tailing activities reveals a poly(UG) polymerase

Ribonucleotidyl transferases (rNTases) add untemplated ribonucleotides to diverse RNAs. We have developed TRAID-seq, a screening strategy in Saccharomyces cerevisiae to identify sequences added to a reporter RNA at single-nucleotide resolution by overexpressed candidate enzymes from different organisms. The rNTase activities of 22 previously unexplored enzymes were determined. In addition to poly(A)- and poly(U)-adding enzymes, we identified a cytidine-adding enzyme that is likely to be part of a two-enzyme system that adds CCA to tRNAs in a eukaryote; a nucleotidyl transferase that adds nucleotides to RNA without apparent nucleotide preference; and a poly(UG) polymerase, Caenorhabditis elegans MUT-2, that adds alternating uridine and guanosine nucleotides to form poly(UG) tails. MUT-2 is known to be required for certain forms of RNA silencing, and mutants of the enzyme that result in defective silencing did not add poly(UG) tails in our assay. We propose that MUT-2 poly(UG) polymerase activity is required to promote genome integrity and RNA silencing. Ribonucleotidyl transferases tethered to an RNA reporter add untemplated RNA tails. TRAID-seq identifies the activities of 22 enzymes, including the addition of poly(UG).
Abstract SY20-01: Linking epigenetics, metabolism, and cancer: Lessons from SIRT6

In recent years, chromatin regulators have emerged as key modulators in cancer. These factors could work as both tumor suppressors and oncogenes, providing plasticity to cancer cells as they adapt to overcome the host responses. In recent years, we discovered that the mammalian histone deacetylase SIRT6 is a key chromatin factor, modulating expression of metabolic, developmental, and ribosomal protein genes. In recent studies, we identified a loss of function mutation in SIRT6 behind a human syndrome of perinatal lethality. In the context of cancer, we found SIRT6 to act as a robust tumor suppressor, by modulating glucose metabolism. As Otto Warburg described decades ago, cancer cells exhibit glycolytic metabolism, where pyruvate, instead of contributing to ATP production in the mitochondria, is converted to lactate even under normoxia conditions. We found SIRT6 as the first chromatin factor in charge of suppressing the Warburg effect in colon cancer. At the cellular level, SIRT6 inactivation leads to increased cellular glucose uptake, higher lactate production and decreased mitochondrial activity. Our results indicate that SIRT6 directly regulates expression of several key glycolytic and ribosomal genes, co-repressing Hif1a and Myc, respectively, and acting as a histone H3 lysine9 (H3K9) and lysine 56 (H3K56) deacetylase to specifically inhibit transcriptional elongation in these genes. Strikingly, we determined in new studies that such glycolytic switch provides an advantage even at the early initiating cancer stem cells stage, in what we identified as the cell-of-origin for the Warburg effect. In addition, we found SIRT6 to act as a robust tumor suppressor in the context of pancreatic cancer. However, in this case, SIRT6 did not influence metabolism, but rather silenced expression of the developmental gene Lin28b, in this way protecting against aggressive undifferentiated pancreatic adenocarcinoma. Our studies highlight the important role epigenetic factors, such as SIRT6, play in protecting against tumor progression by providing “epigenetic plasticity”, inhibiting adaptive responses in transformed cells. References 1. Zhong, L., et al., and Mostoslavsky, R. (2010). The histone deacetylase SIRT6 regulates glucose homeostasis via Hif1a. Cell, 140, 280-293. 2. Sebastian, C., et al. and Mostoslavsky, R. (2012). The Histone Deacetylase SIRT6 is a novel tumor suppressor that controls cancer metabolism. Cell 151, 1185-1199. 3. Kugel., et al. and Mostoslavsky, R. (2016). SIRT6 suppresses pancreatic cancer through control of Lin28b. Cell, 165, 1401-1415. Ferrer et al. 4. Mostoslavsky, R. (2018). An inactivating mutation in the histone deacetylase SIRT6 causes human perinatal lethality. Genes & Dev. 32, 373-388 Citation Format: Raul Mostoslavsky. Linking epigenetics, metabolism, and cancer: Lessons from SIRT6 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY20-01.
Sympathetic-Parasympathetic Interaction and Externalizing Problems in Children with Autism Spectrum Disorder

Children with autism spectrum disorder (ASD) exhibit significant difficulties with emotion regulation and reactivity, which may be linked to underlying psychophysiology. The present study examined associations between autonomic nervous system activity and individual differences in externalizing behavior problems in children with ASD. A multisystem approach was adopted to consider the interplay between markers of sympathetic (electrodermal reactivity-EDA-R) and parasympathetic reactivity (respiratory sinus arrhythmia reactivity-RSA-R) in relation to behavioral challenges. Fifty-two children with ASD ages 6-10 years contributed complete psychophysiological data. Measures of EDA-R and RSA-R (RSA withdrawal) were obtained in response to a laboratory challenge task and parents reported on child externalizing behavior problems using a standardized questionnaire and a structured clinical interview. An equifinality model was supported, with two distinct psychophysiological pathways linked to heightened externalizing behavior problems. Greater RSA-R was associated with more externalizing problems in the context of higher levels of EDA-R, and lower EDA-R was associated with increased externalizing problems at lower levels of RSA-R. Findings underscore the importance of considering the role of psychophysiology in the unfolding of comorbid externalizing problems in children with ASD. Potential implications for tailoring coregulatory supports are discussed. Autism Res 2019, 12: 1805-1816. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children with autism spectrum disorder (ASD) exhibit elevated rates of challenging behavior. This study identified specific psychophysiological profiles (low sympathetic-low parasympathetic reactivity, and high sympathetic-high parasympathetic reactivity) that may place these children at greater risk for behavior problems. Findings have implications for better understanding behavioral challenges in children with ASD, and for tailoring supports to address underlying psychophysiology.
Pinning Efficiency of Artificial Pinning Centers in Superconductor Nanocomposite Films

Nanoscale c-axis aligned one-dimensional artificial pinning centers (1D APCs) can provide strong correlated pinning and therefore reduce the magnetic field (H) orientation-dependence of the critical current density, Jc, an issue stemming from the layered structure of REBa2Cu3O7-δ (RE-123, RE = rare earth including Y, Gd, Sm, etc.). The 1D APCs are self-assembled in RE-123 matrix driven by the strain field initiated from the 1D APC/RE-123 interface strained due to the lattice mismatch. A fundamental question arises as to how the microstructure and pinning efficiency of a 1D APC are affected by the 1D APC/YBCO interface? In order to shed light on this question, two model systems of 1D APCs of BaZrO3 (BZO) and BaHfO3 (BHO) of comparable lateral dimensions (5–6 nm) are selected in our recent studies. However, the interface lattice mismatch with RE-123 such as YBCO and the elastic properties of BZO and BHO differ subtly. The purpose of these studies is to quantify the impact of such differences on the microstructure (especially the areal concentration) and pinning efficiency of the 1D APCs in the BZO (BHO)/YBCO nanocomposite films with APC doping levels varied in the range of 2–6 vol.%. Intriguingly, we have found the impact is substantial. Specifically, the BZO/RE-123 interface is semi-coherent with a large number of dislocations consistent with prior reports, while that of the BHO/RE-123 remains coherent even at high BHO doping levels. This affects the microstructure and pining efficiency of BZO and BHO 1D APCs significantly. The BZO 1D APC concentration and hence matching field B∗ estimated from the TEM characterization increases linearly with the BZO doping, in contrast to a nonlinear trend peaked at 4 vol.% in the BHO case. In addition, a maximum pinning force density (Fpmax) at B//c ~182.0 GNm−3 at Bmax > 9.0 T (instrument limit) and 65 K is obtained in BHO/YBCO nanocomposites, which is significantly higher than the Fpmax~73.0 GNm−3 at Bmax = 5.0 T in its BZO/YBCO counterpart. Moreover, the Bmax/B∗ ratio in both cases decreases monotonically with APC doping. However, it is up to 2.5–3.5 in the BHO/YBCO case in contrast to the maximum of 0.6–0.7 in the BZO/YBCO case. This result reveals the critical effect of APC/RE-123 interface on the microstructure and pinning efficiency of 1D APCs.
What does infant perception tell us about theories of perception

The article begins with a summary of eight well-substantiated conclusions drawn from research on perception in infants that have implications for theories of perception. The following section examines several traditional and modern theories of perception in the light of these conclusions. Finally, some "big issues" that have divided perceptual and cognitive theories are discussed, with the suggestion that research on infants can help reconcile the divided camps. Research on perception in young infants not only flourishes but also presents a challenge to all theories of perception.
Visual, interactive math on the web: bringing the abstract down to Earth

It is one of the contradictions of modern mathematics that simple concepts often require lengthy, highly abstract explanations. In some cases, visual/interactive Java applets can be used to replace these explanations with pictures and experimentation, thus bringing the concepts within reach of undergraduates and high school students. As a bonus, these visual explanations often result in stunning graphic images. The advantages this approach will be explored, using a Web course taught by the workshop presenter as source material.
Protein Sequence Design with a Learned Potential

ABSTRACT The primary challenge of fixed-backbone protein sequence design is to find a distribution of sequences that fold to the backbone of interest. In practice, state-of-the-art protocols often find viable but highly convergent solutions. In this study, we propose a novel method for fixed-backbone protein sequence design using a learned deep neural network potential. We train a convolutional neural network (CNN) to predict a distribution over amino acids at each residue position conditioned on the local structural environment around the residues. Our method for sequence design involves iteratively sampling from this conditional distribution. We demonstrate that this approach is able to produce feasible, novel designs with quality on par with the state-of-the-art, while achieving greater design diversity. In terms of generalizability, our method produces plausible and variable designs for a de novo TIM-barrel structure, showcasing its practical utility in design applications for which there are no known native structures.
Opportunities for Maintenance of Certification to Better Reflect Scope of Practice Among Medical Oncologists

PURPOSE:Critics argue that the American Board of Internal Medicine’s medical oncology Maintenance of Certification examination requires medical oncologists with a narrow scope of practice to spend ...
Abstract MP21: Better Sleep Health is Associated With Greater Weight Loss During a 12-month Behavioral Weight Loss Intervention

Introduction: Sleep is consistently associated with obesity risk, but minimal research has examined its relationship with attempted weight loss. Most of the available evidence has focused on sleep ...
Effect of Phenolic Organics on the Precipitation of Struvite from Simulated Dairy Wastewater

The production of struvite (MgNH4PO4·6H2O) from dairy lagoon wastewater (DW) improves phosphorus (P) resource sustainability and reduces the rate of deposition of P into surface waters. Struvite fo...
Surgical site peptidylarginine deaminase 4 (PAD4), a biomarker of NETosis, correlates with insulin resistance in total joint arthroplasty patients: A preliminary report

While obesity and insulin resistance are known risk factors for wound complications after total joint arthroplasty (TJA), the biologic causes remain to be elucidated. Recently, neutrophil extracellular trap formation (NETosis) was identified as a mediator of delayed wound healing in insulin resistant states. Herein, we explored the relationship between obesity, insulin resistance and biomarkers of NET formation in TJA subjects. We enrolled 14 obese (body mass index [BMI]≥30 kg/m2), and 15 lean (BMI<30 kg/m2) subjects undergoing primary knee or hip TJA. On the day of surgery, skeletal muscle proximal to the operated joint and plasma were collected. Protein abundance of NETosis biomarkers, peptidylarginine deaminase 4 (PAD4) and neutrophil elastase (NE) were assessed in skeletal muscle by immunoblotting and metabolic parameters (glucose, insulin, triglycerides, free fatty acids) and cell-free double-stranded DNA (cf-dsDNA) were assessed in plasma and were correlated with obesity and insulin resistance (as measured by the homeostatic model assessment for insulin resistance). When comparing lean and obese subjects, there were no significant differences in plasma cf-dsDNA or skeletal muscle NE or PAD4 abundance. In contrast, skeletal muscle PAD4 abundance, but not NE or plasma cf-dsDNA, was positively correlated with insulin resistance. Compared to insulin sensitive subjects, insulin resistant TJA subjects have higher expression of PAD4 at the surgical site and therefore may have higher rates of NET formation, which may lead to delayed surgical site wound healing.
Pediatric Emergency Medicine

Pediatric emergency medicine (PEM) is a unique specialty that requires the practitioner to manage a wide spectrum of patients, from the newly born to young adults, presenting with a variety of complaints, including critical illness and injuries. To deliver safe, efficient and high quality care requires skilled clinicians working effectively as a team. Simulation is currently used in an assortment of formats to accomplish teaching goals set by training programs and institutions to assess and improve the care delivered. It can also be used as a valuable tool for systems testing and quality improvement/assessment programs in new and established emergency departments. There are, however, some common challenges associated with integrating and sustaining PEM simulation programs. In this chapter, we will discuss the use of simulation for PEM education, address some of these challenges, and highlight the current benefits and future potential related to this promising methodology.
Freud’s Life and Work: A Historical Horizon

In this chapter, I illustrate through the details of Freud’s life that his theoretical work on a fragmented subjectivity shows it as vulnerable to the affective force of cultural norms, and as such, limits the capacity for self-reflection. I list the psychic mechanisms that he found prevent one from knowing themselves in order to present challenges to traditional moral accounts of a self-mastering identity.