cssi/SciSciGPT-SciSciNet huggingface dataset:
Management of comorbid bipolar disorder and substance use disorders

Background: The comorbidity of substance use disorders (SUDs) in bipolar disorder is among the highest in psychiatric disorders. Evidence-based controlled psychosocial or pharmacological interventi...
A Stable Panchromatic Green Dual Acceptor, Dual Donor Organic Dye for Dye-Sensitized Solar Cells

A novel organic sensitizer (AP3) with dual donors and dual anchor-acceptors based on an electron deficient thieno[3,4-b]pyrazine (TPz) π-bridge was synthesized, which shows an impressively high Jsc of 17.6 mA/cm2 when cosensitized with D35 (12.4 mA/cm2 as a single dye). Device power conversion efficiencies were observed at 7.5% under full sun intensity and in excess of 10% under reduced sun intensity. This novel dye design approach allows for devices showing photostability beyond 500 h for continuous irradiation and a tunable dye structure with an incident power conversion efficiency breadth reaching 800 nm from a simple-to-synthesize organic dye. Dye characterization with cyclic voltammetry, solution and film absorption, and computational analysis are all presented. Additionally, device characterization was performed through IV curves, IPCE, electron lifetime measurements, transient absorption spectroscopy, and current dynamic measurements at varying sun intensities to better understand the origin of the...
Hand-to-hand coupling and strategies to minimize unintentional energy transfer during laparoscopic surgery.

Abstract Background Energy-based devices are used in nearly every laparoscopic operation. Radiofrequency energy can transfer to nearby instruments via antenna and capacitive coupling without direct contact. Previous studies have described inadvertent energy transfer through bundled cords and nonelectrically active wires. The purpose of this study was to describe a new mechanism of stray energy transfer from the monopolar instrument through the operating surgeon to the laparoscopic telescope and propose practical measures to decrease the risk of injury. Methods Radiofrequency energy was delivered to a laparoscopic L-hook (monopolar “bovie”), an advanced bipolar device, and an ultrasonic device in a laparoscopic simulator. The tip of a 10-mm telescope was placed adjacent but not touching bovine liver in a standard four-port laparoscopic cholecystectomy setup. Temperature increase was measured as tissue temperature from baseline nearest the tip of the telescope which was never in contact with the energy-based device after a 5-s open-air activation. Results The monopolar L-hook increased tissue temperature adjacent to the camera/telescope tip by 47 ± 8°C from baseline ( P P P P Conclusions Stray energy transfers from the monopolar “bovie” instrument through the operating surgeon to standard electrically inactive laparoscopic instruments. Hand-to-hand coupling describes a new form of capacitive coupling where the surgeon's body acts as an electrical conductor to transmit energy. Strategies to reduce stray energy transfer include avoiding the same surgeon holding the active electrode and laparoscopic camera or using alternative energy devices.
TOXIC RELEASES FROM PAPER MADE WITH RECOVERED WASTEPAPER VERSUS VIRGIN WOOD FIBER : A RESEARCH NOTE

Toxic Release Inventory (TRI) data were used to compare average releases (kilograms per metric ton) of paper mills using primarily recovered wastepaper versus mills using primarily virgin wood fiber. Annual releases, for 79 mills, of chlorine, chlorine dioxide, chloroform, acids (hydrochloric and sulfuric), volatile organics (methyl ethyl ketone, methanol, and acetone), and ammonia were compared over the years 1987–1992. Both types of mills reported generally lower toxic releases in 1992 than in 1987; however, toxic releases in all categories were significantly lower from mills using recovered wastepaper than from mills using virgin wood fiber, strongly demonstrating that recycling has added benefits beyond reduced resource consumption. These results suggest that environmental policy should concentrate as much on increasing demand for recycled paper and developing wastepaper collection infrastructure as it does on end-of-pipe pollution abatement.
Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding.

Summary Developmentally regulated accessory subunits dictate PRC2 function. Here, we report the crystal structures of a 120 kDa heterotetrameric complex consisting of Suz12, Rbbp4, Jarid2, and Aebp2 fragments that is minimally active in nucleosome binding and of an inactive binary complex of Suz12 and Rbbp4. Suz12 contains two unique structural platforms that define distinct classes of PRC2 holo complexes for chromatin binding. Aebp2 and Phf19 compete for binding of a non-canonical C2 domain of Suz12; Jarid2 and EPOP occupy an overlapped Suz12 surface required for chromatin association of PRC2. Suz12 and Aebp2 progressively block histone H3K4 binding to Rbbp4, suggesting that Rbbp4 may not be directly involved in PRC2 inhibition by the active H3K4me3 histone mark. Nucleosome binding enabled by Jarid2 and Aebp2 is in part accounted for by the structures, which also reveal that disruption of the Jarid2-Suz12 interaction may underlie the disease mechanism of an oncogenic chromosomal translocation of Suz12.
Einleitung: Mit Anderen denken

In einem Interview aus dem Jahr 1969 beruft sich der afroamerikanische Autor James Baldwin an einer entscheidenden Stelle des Gesprachs auf eine Denkerin, mit der er einige Jahre zuvor eine intensive Auseinandersetzung uber die politische Bedeutung der Liebe fur das Verhaltnis von weisen und schwarzen Amerikanern gefuhrt hatte. Baldwin, dessen einnehmendes Gesicht 1963 das Titelblatt des Magazins Time schmuckte, war durch ungewohnliche Essaysammlungen und Romane bekannt geworden, die von bisexuellen, schwarz-weisen Paaren, dem Modernismus der Harlem Renaissance und der widerspruchlichen Existenz schwarzer Amerikaner handeln.
Nanophotonic light sails for relativistic spaceflight by high-power laser beams

We show that designed nanophotonic structures could become multi-band building-block elements of a relativistic light sail, due to their ability to achieve substantial reflectivity and low absorption in the near-IR, significant emissivity in the mid-IR, and a very low mass.
Does the Immigrant Advantage in Overweight/Obesity Persist over Time in Mexican American Youth? NHANES 1988-1994 to 2005-2014

Objective To examine whether the relationship between nativity and overweight/obesity has changed over time among Mexican American children and to investigate the implications of this pattern on overweight/obesity disparities relative to non-Hispanic white children. Methods Using cross-sectional data from Mexican American and non-Hispanic white children aged 4 to 17 years participating in the National Health and Nutrition Examination Surveys (1988-1994 [N = 4,720] and 2005-2014 [N = 7,275]) log-binomial regression was used to calculate prevalence ratios (PRs) of overweight/obesity by nativity status adjusting for sociodemographic covariates, survey period, and a nativity-by-survey period interaction. A separate covariate-adjusted model tested a three-level interaction between ethnicity, nativity, and survey period that included non-Hispanic white children. Results In 1988-1994, foreign-born Mexican Americans had significantly lower prevalence of overweight/obesity compared with US-born Mexican Americans (PR = 0.75, 95% CI: 0.61-0.94). However, by 2005-2014, the nativity gap in overweight/obesity had closed (PR = 0.94, 95% CI: 0.84-1.07). Moreover, while foreign-born Mexican Americans had the lowest levels of overweight/obesity in 1988-1994, by 2005-2014, foreign-born and US-born Mexican Americans had comparable estimates, both significantly higher than that of non-Hispanic white individuals. Conclusions Although overweight/obesity disparities between Mexican Americans and non-Hispanic white Americans had previously been specific to US-born Mexican Americans, disparities in more recent years have extended to foreign-born Mexican Americans.
Harmonic-frequency locking in planar magnetrons

The Multi-Frequency Recirculating Planar Magnetron is a crossed field microwave oscillator capable of generating high powers at two different frequencies. A novel locking phenomenon between the two oscillating structures in the MFRPM has been observed. A new magnetron, the Harmonic Recirculating Planar Magnetron (HRPM) is currently being designed to test the parameter space of this locking phenomenon.
The location of clinically diagnosed secondary caries.

Objective This practice-based study involved private practitioners who reported on the location of 1,100 sites of clinically diagnosed secondary caries. Method and materials The secondary caries was noted on schematic diagrams on which the clinicians made an outline of the restoration and marked the location of the caries with a red pen. The secondary caries was classified as being located gingivally, occlusally/incisally, or at any other location of the restoration. Results Overall, 80% to 90% of the clinically diagnosed secondary caries was reported to be located gingivally, irrespective of the type of restoration or restorative material employed. Class II restorations, analyzed separately, showed a slightly higher relative proportion of occlusal secondary caries on resin composite (16%) than on amalgam (8%) restorations. Conclusion A number of patient, operator, and material factors may contribute to the development of secondary caries and in the differential diagnosis of marginal discrepancies, including secondary caries, at the gingival area of restorations.
Experimental Investigation of Free-Field Implosion of Filament Wound Composite Tubes

The mechanisms and energies associated with the hydrostatic implosion of composite cylinders are investigated experimentally and numerically. Experiments are conducted in a large pressure vessel, designed as to provide an adequate reflection-free window to best capture pressure waves resulting from the collapse. Both glass-fiber/polyester and carbon-fiber/epoxy filament wound thin-walled (R/t > 15) tubes are tested with varying L/D ratios to explore the effect of geometry on the collapse pressure and mechanics of the collapse. 3D Digital Image Correlation (DIC) is used to capture the full-field displacements and strains during the implosion event, and dynamic pressure transducers are employed to measure the pressure pulse generated by the collapse. Computational models are developed to verify and better understand key mechanisms of failure during hydrostatic buckling.
The Geography of Ethnic Violence

We consider the conditions of peace and violence among ethnic groups, testing a theory designed to predict the locations of violence and interventions that can promote peace. Violence arises at boundaries between regions that are not sufficiently well defined. We model cultural differentiation as a separation of groups whose members prefer similar neighbors with a characteristic group size at which violence occurs. Application of this model to the area of the former Yugoslavia and to India accurately predicts the locations of reported conflict. Characterizing the model’s success in predicting peace requires examples where peace prevails despite diversity. Switzerland is recognized as a country of peace, stability, and prosperity. This is surprising because of its linguistic and religious diversity that in other parts of the world lead to conflict and violence. Here we analyze how peaceful stability is maintained. Our analysis shows that peace does not depend on integrated coexistence, but rather on well-defined topographical and political boundaries separating linguistic and religious groups, respectively. In exactly one region, a porous mountain range does not adequately separate linguistic groups and violent conflict has led to the recent creation of the canton of Jura. Our analysis supports the hypothesis that violence between groups can be inhibited by both physical and political boundaries. A similar analysis of the area of the former Yugoslavia shows that during widespread ethnic violence existing political boundaries did not coincide with the boundaries of distinct groups, but peace prevailed in specific areas where they did coincide.
Sleep problems and suicide risk in youth: A systematic review, developmental framework, and implications for hospital treatment

Abstract Objective Sleep problems are transdiagnostic symptoms that confer significant risk for suicidal thoughts and behaviors (STBs) in adults. However, less is known about the sleep-STB association in adolescence—a developmental period when rates of STBs increase drastically, and sleep problems may be particularly pernicious. This article provides a systematic review of research on the sleep-STB association in youth, an overview of changes in sleep regulation during adolescence that may make sleep problems particularly detrimental for youth, and a discussion of the clinical implications of the sleep-STB association for hospitalized youth. Method The systematic review included all longitudinal studies in which sleep problems were examined as prospective predictors of STBs in adolescents (aged 10–24 years). The search was conducted on December 1, 2017 using PsychINFO, PubMed, and Web of Science databases. Results Ten studies qualified for inclusion in this review. Of these, seven studies found at least one type of sleep problem significantly predicted a STB outcome. Conclusions Although findings are mixed, growing research suggests that sleep problems may be a unique risk factor for STBs in youth. Sleep problems may be particularly important intervention target because they are easily assessed across healthcare settings and are amenable to treatment.
Insights into the Regulatory Properties of Human Adenylyl Cyclase Type 9

Membrane-bound adenylyl cyclase (AC) isoforms have distinct regulatory mechanisms that contribute to their signaling specificity and physiologic roles. Although insight into the physiologic relevance of AC9 has progressed, the understanding of AC9 regulation is muddled with conflicting studies. Currently, modes of AC9 regulation include stimulation by Gαs, protein kinase C (PKC) βII, or calcium-calmodulin kinase II (CaMKII) and inhibition by Gαi/o, novel PKC isoforms, or calcium-calcineurin. Conversely, the original cloning of human AC9 reported that AC9 is insensitive to Gαi inhibition. The purpose of our study was to clarify which proposed regulators of AC9 act directly or indirectly, particularly with respect to Gαi/o. The proposed regulators, including G proteins (Gαs, Gαi, Gαo, Gβγ), protein kinases (PKCβII, CaMKII), and forskolin, were systematically evaluated using classic in vitro AC assays and cell-based cAMP accumulation assays in COS-7 cells. Our studies show that AC9 is directly regulated by Gαs with weak conditional activation by forskolin; other modes of proposed regulation either occur indirectly or possibly require additional scaffolding proteins to facilitate regulation. We also show that AC9 contributes to basal cAMP production; knockdown or knockout of endogenous AC9 reduces basal AC activity in COS-7 cells and splenocytes. Importantly, although AC9 is not directly inhibited by Gαi/o, it can heterodimerize with Gαi/o-regulated isoforms, AC5 and AC6.
CLINICAL IMPACT OF ANKLE-BRACHIAL INDEX IMPROVEMENT AFTER ENDOVASCULAR THERAPY FOR PERIPHERAL ARTERIAL DISEASE

Predictive ability of changes in ankle-brachial index (ABI) after revascularization for long-term clinical outcomes has not been well evaluated to date. From January 2004 to October 2017, 2517 consecutive patients (4245 limb) underwent endovascular therapy (EVT) for aorto-iliac and/or
A Political Listing: A Rant, a Confession, and a Hope:

In this coupling of autoethnography and poetic inquiry, I offer a poem in three parts: the first, a rant; the second, a confession; and the third, a hope. Each part identifies a different way I am ...
A 3D-Printed Simulator and Teaching Module for Placing S2-Alar-Iliac Screws

Background The concept of the S2-alar-iliac (S2AI) screw was developed approximately one decade ago and has rapidly become an important component of spinal arthrodesis. Two challenges to placing S2AI screws are gaining an intuition for free-hand screw placement trajectory and acquisition of the appropriate radiograph to both guide screw placement and diagnose misplacement. Objective To present the design and manufacture of an S2AI screw placement simulator and teaching module that addresses both challenges. Methods This simulator involves using a 3D printer to create a life-sized pelvis. Participants first used this print to practice placing free-hand S2AI screws. Then participants used another print to practice taking radiographs showing the posterior superior iliac spine-anterior superior iliac spine corridor (teardrop) view. Results The accuracy of screw placement increased from 17 to 80% on the left side and 7 to 100% on the right side. The number of radiographs taken by each participant to obtain the teardrop view decreased after practice with the simulator compared to baseline. Conclusion Practice with the S2AI simulator led to an improved intuition of an appropriate free-hand S2AI screw trajectory and a decrease in the number of radiographs needed for obtaining the correct diagnostic view.
Making Herstory: Cherokee Women's Stickball

Stickball amongst the Eastern Band of Cherokee Indians is a sporting tradition that precedes written records. Historical and academic texts have focused on men’s participation in the sport. However...
Boundary Layer Quasi-Equilibrium Limits Convective Intensity Enhancement from the Diurnal Cycle in Surface Heating

AbstractA combination of cloud-permitting model (CPM) simulations, satellite, and reanalysis data are used to test whether the diurnal cycle in surface temperature has a significant impact on the i...
Design and alignment of an all-spherical unobscured four-mirror image relay for an ultra-broadband sub-petawatt laser

We describe the design and alignment of an unobscured reflective image relay for use in an ultra-broadband half-petawatt laser system in development at the University of Rochester's Laboratory for Laser Energetics. The design consists of four spherical mirrors in an unobscured configuration. We show the theoretical basis for such a four-mirror design using first-order optical matrix methods and nodal aberration theory. We also describe the process of aligning this design in a test bed and show the results of this alignment method. We were able to achieve a diffraction-limited nominal design. Upon aligning the design in our test bed, we were able to successfully align the design to achieve our target wavefront error of less than 0.3 waves peak to valley and 0.07 waves rms at the central laser-operating wavelength of 910 nm.
An evaluation of the impact of clinical bacterial isolates on epithelial cell monolayer integrity by the electric Cell-Substrate Impedance Sensing (ECIS) method.

Abstract Virulence is the relative capacity of a pathogenic microorganism to cause damage in susceptible host cells such as those found in airway passages and the gut. In this study, the effect of clinical bacterial isolates on the monolayer integrity of cultured human alveolar basal epithelial cells (A549) was evaluated using the Electric Cell-Substrate Impedance Sensing (ECIS) system. ECIS is a morphological biosensor which records electrical properties of cell-covered microelectrodes in an AC circuit including impedance (ohm), resistance (ohm), and capacitance (μFarad). In the current study, fluctuations in the electrical properties of cell-covered microelectrodes reflect dynamic changes in cell morphology resulting from disrupted cell monolayers following exposure to bacteria. Using the ECIS system, real-time changes of cell morphology and disruption of monolayer integrity of cell-cultures in vitro were revealed for A549 cells infected with either Pseudomonas aeruginosa , ESBL Escherichia coli, Staphylococcus aureus (MRSA), or Enterococcus (VRE). We determined empirically that the optimal signal response was obtained for resistance (ohm) measurements at 4000 hertz. Following infection of A549 cells, the data revealed that Pseudomonas aeruginosa resulted in little change in microelectrode resistance (ohm @4 kHz) as compared to pathogen-free controls within the first 12 h. In contrast, E. coli , MRSA , and VRE caused significant changes in electrode resistance (ohm @4 kHz) values in the infected cells compared to controls over the first 5 h. Resistance (ohm @4 kHz) changes were also observed in cell monolayers infected with different bacterial concentrations for all isolates over 24 h. The highest concentration of bacteria caused the measured resistance (ohm @4 kHz) to drop faster than its' immediate lower concentration, suggesting a dose-dependent effect. Compared to live bacteria, cells exposed to heat-killed bacteria did not show significant changes in resistance (ohm @4 kHz) over 48 h post-exposure. Functionally, cytokine responses were different between cells treated with live and heat-killed bacteria. Of note, live bacteria induced IFNγ, IL-13, and IL-1β production in A549 cells, whereas heat-killed bacteria induced IL-8 production suggesting a differential interaction with cells that could reveal the underlying causes of resistance (ohm @4 kHz) changes. Our findings indicate that ECIS provides a means to quantify, automate, and measure bacterial virulence , which may have broader implications governing the course of treatment compared to traditional methods alone.
Molecular mechanism of an antagonistic antibody against glucose-dependent insulinotropic polypeptide receptor.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in regulating glucose and lipid metabolism. GIP receptor (GIPR) antagonism is believed to offer therapeutic potent...
Characterization of exome variants and their metabolic impact in 6,716 American Indians from Southwest US

Abstract Applying whole exome sequencing (WES) to populations with unique genetic architecture has the potential to reveal novel genes and variants associated with traits and diseases. We sequenced and analyzed the exomes of 6,716 individuals from an American Indian population in Southwest US (Southwestern American Indian, or SWAI) with well-characterized metabolic traits. We found that individuals of SWAI have distinct allelic architecture compared to individuals with European and East Asian ancestry, with many predicted loss-of-function (pLOF) and nonsynonymous variants that were highly enriched or private in SWAI. We evaluated gene-level associations with metabolic traits using pLOF and nonsynonymous variants in SWAI. Many of the candidate genes from previous GWAS studies for body mass index, type 2 diabetes, and plasma lipid levels were associated with respective traits in SWAI. Notably, these associations were mainly driven by pLOF and nonsynonymous variants that are unique or highly enriched in American Indians, many of which have not been observed in other populations or functionally characterized. Our study illustrates the utility and potential of WES in American Indians to prioritize candidate effector genes within GWAS loci and to find novel variants in known diseases genes with potential clinical impact.
Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000–2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan–Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). The USNETSG database included 2022 patients. Of those, 1425 were aged 18–64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32–5.48, p = 0.006]. Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.
Solubility and Diffusivity of Bromodifluoromethane (Halon-1201) in Imidazolium Ionic Liquids: [C2C1im][Tf2N], [C4C1im][BF4], and [C4C1im][PF6]

The solubility and diffusivity of bromodifluoromethane (CHF2Br, Halon-1201) were measured in three ionic liquids (ILs), [C2C1im][Tf2N], [C4C1im][BF4], and [C4C1im][PF6], using an intelligent gravim...
Self-healing and self-cleaning clear coating.

Abstract Coatings exhibiting both self-cleaning and self-healing properties are envisioned for a wide range of applications. Herein we report a simple fabrication approach toward poly(urea-urethane) (PU) coatings having self-healing and self-cleaning properties. The self-cleaning component is a poly(dimethylsiloxane) (PDMS), which is affordable in cost and also has a lower environmental footprint relative to its fluorinated counterpart. The self-healing properties are imparted by dynamic urea bonds of the matrix. The obtained surfaces are evaluated for their anti-smudge properties such as water-, oil- and ink-repellency, as well as optical properties. The self-healing properties of these coatings are evaluated by making scores with a doctor blade and monitoring the healing under different conditions using optical microscopy. The resultant coatings are also investigated for their good mechanical properties. The surface chemical compositions are determined x-ray photoelectron spectroscopy, while atomic force microscopy is used for microstructural analysis of these coatings.
Formation and migration of H3O+ and OH− ions at the water/silica and water/vapor interfaces under the influence of a static electric field: a molecular dynamics study

The atomistic mechanisms of proton transport under the influence of a static electric field at various angles to the water/silica glass interface were simulated using a reactive, all-atom potential. The fields were shown to change the structure of the 20 A water film significantly, as well as the concentrations and distributions of H3O+ and OH- ions in the film. The field was less than that needed for the dissociation of the water molecule, so the presence of these ions was caused by the interactions with the silica surface. While excess protons at certain silica surface sites can be highly unstable (rattling between adjacent surface sites), protons attached to surface sites that only sample other surface sites are shown to be less mobile in comparison to H3O+ and OH- ions in the water film. After creation of H3O+ and OH- at the silica surface, these ions were observed to have greater mobility away from the glass surface compared to near it. Fields parallel to the glass surface were shown to greatly enhance mobilities of OH- ions. Very high ion mobilities were observed at the water-vapor interface under field orientations of -45° and +45° (relative to the surface plane) respectively. These field orientations are able to pin charges to the vapor interface in addition to dragging them along it. Both vehicular and structural diffusion of the H3O+ and OH- ions were determined as a function of location in the water relative to the silica and vapor interfaces. The results indicate the importance of the orientation of a field to a glass surface and the water vapor interface on proton and ion transport in unsaturated pores.
Handling “Space Debris” under the International Space Treaties Regime: Case Studies Analysis

A fundamental risk for any space mission is a collision with "space debris" – nonfunctioning artificial objects that keep in orbit around Earth. Besides collisions that may prove fatal to individua...
Detoxication versus Bioactivation Pathways of Lapatinib In Vitro: UGT1A1 Catalyzes the Hepatic Glucuronidation of Debenzylated Lapatinib.

O-Dealkylation of the tyrosine kinase inhibitor lapatinib by cytochrome P450 3A enzymes is implicated in the development of lapatinib-induced hepatotoxicity. Conjugative metabolism of debenzylated lapatinib (M1) via glucuronidation and sulfation is thought to be a major detoxication pathway for lapatinib in preclinical species (rat and dog), limiting formation of the quinoneimine reactive metabolite. Glucuronidation of M1 by human recombinant UDP-glucuronosyltransferases (UGTs) has been reported in vitro; however, the relative UGT enzyme contributions are unknown, and the interspecies differences in the conjugation versus bioactivation pathways of M1 have not been fully elucidated. In the present study, reaction phenotyping experiments using human recombinant UGT enzymes and enzyme-selective chemical inhibitors demonstrated that UGT1A1 was the major hepatic UGT enzyme involved in lapatinib M1 glucuronidation. Formation of the M1-glucuronide by human liver microsomes from UGT1A1-genotyped donors was significantly correlated with UGT1A1 activity as measured by 17β-estradiol 3-glucuronidation (R2 = 0.90). Interspecies differences were found in the biotransformation of M1 in human, rat, and dog liver microsomal and 9000g supernatant (S9) fractions via glucuronidation, sulfation, aldehyde oxidase–mediated oxidation, and bioactivation to the quinoneimine trapped as a glutathione (GSH) conjugate. Moreover, we demonstrated the sequential metabolism of lapatinib in primary human hepatocytes to the M1-glucuronide, M1-sulfate, and quinoneimine-GSH conjugate. M1 glucuronidation was highly correlated with the rates of M1 formation, suggesting that O-dealkylation may be the rate-limiting step in lapatinib biotransformation. Interindividual variability in the formation and clearance pathways of lapatinib M1 likely influences the hepatic exposure to reactive metabolites and may affect the risk for hepatotoxicity. SIGNIFICANCE STATEMENT We used an integrated approach to examine the interindividual and interspecies differences in detoxication versus bioactivation pathways of lapatinib, which is associated with idiosyncratic hepatotoxicity. In addition to cytochrome P450 (P450)-mediated bioactivation, we report that multiple non-P450 pathways are involved in the biotransformation of the primary phenolic metabolite of lapatinib in vitro, including glucuronidation, sulfation, and aldehyde oxidase mediated oxidation. UGT1A1 was identified as the major hepatic enzyme involved in debenzylated lapatinib glucuronidation, which may limit hepatic exposure to the potentially toxic quinoneimine.
Abstract rules for complex systems

This article addresses the question—What is the structure of rules required to undergird a complex dynamic system of actions such as the market economy? The idea of simplicity does not adequately highlight the particular characteristics that the rules must possess. Instead, this article explores the key requirement of abstractness. This is a multifaceted concept. It manifests itself in the abstract formulation of the antecedent clause in rules, and in ends-independence, decomposability, and generality. These requirements do not directly influence the size or scope of the state but they may indirectly do so by precluding certain forms of intervention.
Sparsity Promoting Frequency Sampling Method for Estimation of Displacement and Self-Mixing Interferometry Parameters

This paper exploits the difference in amplitude spectrum of perturbed and unperturbed phase of self-mixing (SM) laser, to propose a new method for estimation of coupling factor (C), line-width enhancement factor (LEF), as well as displacement of the vibrating target in three major feedback regimes, i.e, weak-, moderate- and strong-feedback regimes. This result thus fills the gap in limitation of previous methods restricted to fewer regimes. The displacement of target is assumed to be bandlimited and sparse in frequency domain. The proposed algorithm showed an average of 1.0168 nm RMS error in displacement estimation corresponding to single- and multi-tone vibrations of amplitudes varying from 3 to 30 times that of laser’s wavelength, with percentage error of 1.15% and 3.31% in C and LEF estimations, from simulated SM laser signals. Using an SM sensor based on a laser diode emitting at 785 nm wavelength, the proposed method has achieved an average RMS error of 21 nm in weak-, moderate- and strong-feedback regimes, corresponding to a vibrating target of 5 micrometer peak-peak amplitude.
A defesa noticiosa do status quo

News is "a highly unpredictable medium", decisions on news coverage should be taken quickly, time pressure leaves little room for elaborate decision-making. Journalists have to master a space of considerable autonomy in the selection and construction of the news and realise that reactions can only be obtained by developing other and new feedback processes, interaction processes whose great advantage is to create bonds. Gans argues that journalists analyse the current political-economic system from a "natural state-of-affairs perspective", with the search for newsworthy sources focusing on the power structure and the news defence of the status quo.
National Trends in Heart Failure Hospitalizations and Readmissions From 2010 to 2017.

Author(s): Agarwal, Manyoo A; Fonarow, Gregg C; Ziaeian, Boback | Abstract: ImportancePrevious studies have described the secular trends of overall heart failure (HF) hospitalizations, but the literature describing the national trends of unique index hospitalizations and readmission visits for the primary management of HF is lacking.ObjectivesTo examine contemporary overall and sex-specific trends of unique primary HF (grouped by number of visits for the same patient in a given year) and 30-day readmission visits in a large national US administrative database from 2010 to 2017.Design, setting, and participantsThis cohort study used data from all adult hospitalizations in the Nationwide Readmission Database from January 1, 2010, to December 31, 2017, with a primary diagnosis of HF. Data analyses were conducted from March to November 2020.ExposuresAdmission for a primary diagnosis of HF at discharge.Main outcomes and measuresUnique and overall hospitalizations with a primary diagnosis of HF and postdischarge readmissions. Unique primary HF hospitalizations were grouped by number of visits for the same patient in a given year.ResultsThere were 8 273 270 primary HF hospitalizations with a single primary HF admission present in 5 092 626 unique patients, and 1 269 109 had 2 or more HF hospitalizations. The mean age was 72.1 (95% CI, 72.0-72.3) years, and 48.9% (95% CI, 48.7-49.0) were women. The primary HF hospitalization rates per 1000 US adults declined from 4.4 in 2010 to 4.1 in 2013 and then increased from 4.2 in 2014 to 4.9 in 2017. The rates per 1000 US adults for postdischarge HF readmissions (1.0 in 2010 to 0.9 in 2014 to 1.1 in 2017) and all-cause 30-day readmissions (0.8 in 2010 to 0.7 in 2014 to 0.9 in 2017) had similar trends.Conclusions and relevanceIn this analysis of a nationally representative administrative data set, for primary HF admissions, crude rates of overall and unique patient hospitalizations declined from 2010 to 2014 followed by an increase from 2014 to 2017. Additionally, readmission visits after index HF hospitalizations followed a similar trend. Future studies are needed to verify these findings to improve policies for HF management.
Phase II Study of Verubulin (Azixa, MPC-6827) with Radiation Therapy and Temozolomide in Newly Diagnosed Glioblastoma Multiforme Patients: Incomplete Report on Safety, Tolerability and Responses (P3.125)

OBJECTIVE: To establish safety, tolerability and efficacy of Azixa when combined with standard of care therapy (SOC) (RT/TMZ) in newly diagnosed GBM patients. Such combination may improve survival of patients with newly diagnosed GBM. BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumors with a median overall survival of 14.6 months despite surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Anti-angiogenesis therapy, bevacizumab (BV), has emerged as a treatment option for progressive GBM. Azixa is a novel microtubule destabilizer and functions as a potent cytotoxin and a vascular disrupting agent. It evades multidrug resistance pumps and achieves high CNS concentrations. It is potently active in multiple xenograft models. Phase I data had determined MTD at 3.3 mg/m 2 and showed no significant toxicity. A phase II study of Azixa for recurrent GBM with or without BV had demonstrated no significant adverse effect either. DESIGN/METHODS: Part A is an open-label standard 3+3 dose finding design to establish the MTD of Azixa (doses 2.2, 3.3 or 2.8 mg/m 2 ) with SOC. Part B was planned as an open-label, randomized, 2-arm, comparative trial. Part A consists of SOC with Azixa (weekly for 5 weeks out of 6 weeks period) followed by a 28-day break, then six cycles of TMZ (5 days on/23 days off/cycle) with Azixa (weekly for 3 weeks/cycle) for a total of 6 cycles. Primary endpoints are safety, tolerability and 9-month progression-free survival (PFS-9). RESULTS: The trial was terminated in March, 2012 by the sponsor for financial reason. Incomplete data demonstrated that Azixa is well tolerated and it is safe to use with SOC. Three patients are long term survivors over 3 years. One of them is still alive without evidence of disease. CONCLUSIONS: Azixa is well tolerated and it warrants further investigaiton. Study Supported by: Myrexis, Inc. Disclosure: Dr. Zhu has received personal compensation for activities with Novocure and Prime Oncology. Dr. Kesari has received personal compensation for activities with Enzon Pharmaceuticals, Bristol-Myers Squibb Company and Genentech, Inc. as a speaker and/or advisory board member. Dr. Recht has received personal compensation for activities with Pharmacyclics, Inc.
Database Replication Using Epidemic Communication

There is a growing interest in asynchronous replica management protocols in which database transactions are executed locally, and their effects are incorporated asynchronously on remote database copies. In this paper we investigate an epidemic update protocol that guarantees consistency and serializability in spite of a write-anywhere capability and conduct simulation experiments to evaluate this protocol. Our results indicate that this epidemic approach is indeed a viable alternative to eager update protocols for a distributed database environment where serializability is needed.
C Wolf - A Toolset for Extracting Models from C Programs

We report on the design, implementation, and use of C Wolf, a toolset which extracts finite labeled transition systems from C programs. The extraction process is guided by user input on how a program should be abstracted, and what events should be made observable to the user. The output is an abstracted model suitable for input to the Concurrency Workbench. Additionally, facilities are provided to carry out simple observational equivalence-preserving transformations which reduce the size of the generated model. Finally, we report our experiences in using the toolset to analyze the GNU i-protocol(V ersion 1.04) and the BSD ftp daemon (Version 0.3.3).
Bistable dynamics between forest removal and landslide occurrence

It is well documented that deforestation results in an increase in landslide frequency due to the control that forest roots have on slope stability. The loss of forest vegetation leads to a reduction in soil cohesion and a decrease in the shear strength of the soil profile. As a result, the slope becomes more susceptible to landsliding and the return time of landslides decreases. When a landslide removes the soil profile, there may not be adequate time for seedlings to grow and enhance soil stability. In this study, we investigate whether bistable dynamics emerge from the interaction of forest vegetation with the formation and accumulation of colluvial deposits in soil-mantled landscapes. To that end, we develop deterministic and stochastic models of landslide occurrence with a dynamic vegetation component. Results show that bistability exists for the deterministic case for both steep and shallow hollows under event and supply limited conditions. However, for the stochastic case, the randomness of landslide occurrence largely changed the states of the system such that the system only exhibited one stable state, which was the fully vegetated condition. Examining different management practices under stochastic conditions showed that the system eventually recovered; however, management practices influenced the recovery time of the forest. Thus, different management practices could render the land in a state of low vegetation over economically significant time periods.
Truth or consequences in the diagnosis of substance use disorders

Aims This commentary critically evaluates the use of substance-related negative psychosocial and health consequences to define and diagnose alcohol and other substance use disorders. Methods Narrative review. Results The consequences of substance use cause much suffering and are major public health and economic problems. However, there are a number of conceptual and measurement problems with using consequences as diagnostic criteria for substance disorders. Data indicate that substance-related consequences introduce systematic bias and degrade the validity of diagnostic systems. Conclusions Negative psychosocial and health consequences of substance use should play a fundamentally reduced role in modern diagnostic systems for, and definitions of, addictive disorders.
Guiding Attention Produces Inferences in Diagram-Based Problem Solving

Many eye-tracking studies have shown that visual attention patterns during diagram-based problem solving, measured by eye movements, reveal critical aspects of the problem solving process that traditional measures like solution time and accuracy cannot address. In our first experiment (n = 14), we use this method during the solution of a widely-studied high level reasoning problem, Duncker's (1945) radiation problem, to show that differences in visual attention to a particular diagram feature corresponds with correctly solving the problem. We then extend these findings in a second experiment (n = 81) to evaluate cognative sensitivity to perceptual changes in the diagram. We show that problem solvers are highly sensitive to the diagram structure, and that the shifts in attention that result from subtle perceptual changes in the diagram appear to have a dramatic positive effect on reasoning.
Generation of AuPd22/Au2Pd21 analogues of the high-nuclearity Pd23(CO)20(PEt3)10 cluster containing 19-atom centered hexacapped-cuboctahedral (ν2-octahedral) metal fragment: structural-to-synthesis approach concerning formation of Au2Pd21(CO)20(PEt3)10

Reactions of Pd(PEt3)2Cl2 and Au(PPh3)Cl in DMF with NaOH under CO atmosphere gave rise to the unique capped three-shell homopalladium Pd145(CO)x(PEt3)30 (x ∼ 60) and two neutral Au–Pd clusters: Au2Pd21(CO)20(PEt3)10 (1) and Au2Pd41(CO)27(PEt3)15 (following article). Similar reactions with Pd(PMe3)2Cl2 being used in place of Pd(PEt3)2Cl2 afforded Au2Pd21(CO)20(PMe3)10 (2), the trimethylphosphine analogue of 1, and the electronically equivalent [AuPd22(CO)20(PPh3)4(PMe3)6]− monoanion (3) as the [PPh4]+ salt. Each of these three air-sensitive 23-atom heterometallic Au–Pd clusters was obtained in low yields (7–25%); however, their geometrical similarities with the known cuboctahedral-based homopalladium Pd23(CO)20(PEt3)10 (4), recently obtained in good yields from Pd10(CO)12(PEt3)6, suggested an alternative preparative route for obtaining 1. This “structure-to-synthesis” approach afforded 1 in 60–70% yields from reactions of Pd10(CO)12(PEt3)6 and Au(PPh3)Cl in DMF with NaOH under N2 atmosphere. Both the compositions and atomic arrangements for 1, 2 and 3 were unambiguously established from low-temperature single-crystal CCD X-ray crystallographic determinations in accordance with their nearly identical IR carbonyl frequencies. Cluster 1 was also characterized by 31P{1H} NMR, cyclic voltammetry (CV) and elemental analysis. The virtually identical Au2Pd21 core-architectures of 1 and 2 closely resemble that of 4, which consists of a centered hexa(square capped)-cuboctahedral Pd19 fragment of pseudo-Oh symmetry that alternatively may be viewed as a centered Pd19 ν2-octahedron (where νn designates (n + 1) equally spaced atoms along each edge). [AuPd22(CO)20(PPh3)4(PMe3)6]− (3) in the crystalline state ([PPh4]+ salt) consists of two crystallographically independent monoanions 3A and 3B; a superposition analysis ascertained that their geometries are essentially equivalent. A CV indicates that 1 reversibly undergoes two one-electron reductions and two one-electron oxidations; these reversible redox processes form the basis for an integrated structural/electronic picture that is compatible with the existence of the electronically-equivalent 1–3 along with the electronically-nonequivalent 4 (with two fewer CVEs) and other closely related species.
Capture and enumeration of mRNA transcripts from single cells using a microfluidic device

Accurate measurement of RNA transcripts from single cells will enable the precise classification of cell types and characterization of the heterogeneity in cell populations that play key roles in normal cellular physiology and diseases. As a step towards this end, we have developed a microfluidic device and methods for automatic hydrodynamic capture of single mammalian cells and subsequent immobilization and digital counting of polyadenylated mRNA molecules released from the individual cells. Using single-molecule fluorescence imaging, we have demonstrated that polyadenylated mRNA molecules from single HeLa cells can be captured within minutes by hybridization to polydeoxyribothymidine oligonucleotides covalently attached on the glass surface in the device. The total mRNA molecule counts in the individual HeLa cells are found to vary significantly from one another. Our technology opens up the possibility of direct digital enumeration of RNA transcripts from single cells with single-molecule sensitivity using a single integrated microfluidic device.