cssi/SciSciGPT-SciSciNet huggingface dataset:
Improved tumor vascular function following high-dose epidermal growth factor receptor tyrosine kinase inhibitor therapy

Purpose—To determine if inhibitors of the human growth factor receptor (HER) family can be used to enhance tumor vascular permeability and perfusion and optimize the efficacy of cytotoxic chemotherapeutics. Poor tumor vascular function limits the delivery and efficacy of cancer chemotherapeutics and HER family tyrosine kinases mediate tumor-endothelial signaling in both of these compartments. Materials and Methods—BT474 human breast cancer tumors were established in mice and the biologic effects of the HER tyrosine kinase inhibitor (TKI) gefitinib on tumor vascular function was determined by dynamic contrast enhanced MRI (DCE-MRI), and on tumor vascular architecture and perfusion by immunofluorescence microscopy. Results—A brief dose of gefitinib enhances the anti-tumor activity of paclitaxel in vivo but not in cell culture, suggesting that its chemo enhancing activity involves the in vivo microenvironment. A brief high dose of gefitinib induces a decrease in endothelial transfer constant Kps and a concomitant increase in tumor fractional plasma volume (fPV). These changes are accompanied by a rapid reduction in tumor volume likely due to decreased tumor edema, and modestly improved tumor vascular architecture and perfusion on microscopy. Conclusion—These data suggest that HER family TKIs have the potential to optimize the tumor microenvironment for delivery of cytotoxic chemotherapeutics.
Optimization of combinational and sequential logic circuits for low power using precomputation

Precomputation is a recently proposed logic optimization technique which selectively disables the inputs of a sequential logic circuit, thereby reducing switching activity and power dissipation, without changing logic functionality. In this paper, we present new precomputation architectures for both combinational and sequential logic and describe new precomputation-based logic synthesis methods that optimize logic circuits for low power. We present a general precomputation architecture for sequential logic circuits and show that it is significantly more powerful than the architectures previously treated in the literature. In this architecture, output values required in a particular clock cycle are selectively precomputed one clock cycle earlier, and the original logic circuit is "turned off" in the succeeding clock cycle. The very power of this architecture makes the synthesis of precomputation logic a challenging problem and we present a method to automatically synthesize precomputation logic for this architecture. We introduce a powerful precomputation architecture for combinational logic circuits that uses transmission gates or transparent latches to disable parts of the logic. Unlike in the sequential circuit architecture, precomputation occurs in an early portion of a clock cycle, and parts of the combinational logic circuit are "turned off" in a later portion of the same clock cycle. Further we are not restricted to perform precomputation on the primary inputs. Preliminary results obtained using the described methods are presented. Up to 66 percent reductions in switching activity and power dissipation are possible using the proposed architectures. For many examples, the proposed architectures result in significantly less power dissipation than previously developed methods.
Volumetric Modeling in Laser BPH Therapy Simulation

In this paper, we introduce a novel application of volume modeling techniques on laser Benign Prostatic Hyperplasia (BPH) therapy simulation. The core technique in our system is an algorithm for simulating the tissue vaporization process by laser heating. Different from classical volume CSG operations, our technique takes experimental data as the guidance to determine the vaporization amount so that only a specified amount of tissue is vaporized in each time. Our algorithm uses a predictor-corrector strategy. First, we apply the classical CSG algorithm on a tetrahedral grid based distance field to estimate the vaporized tissue amount. Then, a volume-correction phase is applied on the distance field. To improve the performance, we further propose optimization approaches for efficient implementation.
Structural modifications of a 3-methoxy-2-aminopyridine compound to reduce potential for mutagenicity and time-dependent drug-drug interaction.

Abstract ( S )-1-((4-(3-(6-Amino-5-methoxypyridin-3-yl)-1-isopropyl-1 H -pyrazol-4-yl)pyrimidin-2-yl)amino)propan-2-ol, 1 , was recently identified as a potent inhibitor of the oncogenic kinase bRAF. Compounds containing 3-methoxy-2-aminopyridine, as in 1 , comprised a promising lead series because of their high ligand efficiency and excellent ADME profile. However, following metabolic oxidation, compounds in this series also demonstrated two significant safety risks: mutagenic potential and time-dependent drug–drug interaction (TDI). Metabolite identification studies revealed formation of a reactive metabolite. We hypothesized that minimizing or blocking the formation of such a metabolite would mitigate the safety liabilities. Our investigation demonstrated that structural modifications which either reduced the electron density of the 3-methoxy-2-aminopyridine ring or blocked the reactive site following metabolic oxidation were successful in reducing TDI and AMES mutagenicity.
Quantitative measurement of Ca2+ and Zn2+ in mammalian cells using genetically encoded fluorescent biosensors

Genetically encoded, ratiometric, fluorescent biosensors can be used to quantitatively measure intracellular ion concentrations in living cells. We describe important factors to consider when selecting a Ca(2+) or Zn(2+) biosensor, such as the sensor's dissociation constant (K(d')) and its dynamic range. We also discuss the limits of quantitative measurement using these sensors and reasons why a sensor may perform differently in different biological systems or subcellular compartments. We outline protocols for (1) quickly confirming sensor functionality in a new biological system, (2) calibrating a sensor to convert a sensor's FRET ratio to ion concentration, and (3) titrating a sensor in living cells to obtain its K(d') under different experimental conditions.
Pilot Study of Burin Use-Wear from Shanidar Cave, Iraq

ABSTRACTMicroscopic use-wear is present on all four burins studied. The four heavily patinated chert artifacts from the Upper Paleolithic Baradostian horizon, radiocarbon date between 28,000 and 33,000 B.P. Burin usage originates and extends from the trihedral bit to adjacent facets; probable haft wear traces are present on three of the four tools.
Functionalization of η1,η2-Bridging Cyaphide (C⋮P)- Ligands: Trinuclear η1,η1,η2-Bridging Cyaphide and Dinuclear Bridging Isocyaphide (C⋮PR) Complexes of Platinum†

The oxidative addition reaction of Pt(PEt3)4 with Cl2CPN(SiMe3)2 at low temperature (−50 °C) forms the η1-phosphavinyl complex cis-Cl(Et3P)2Pt[C(Cl)PN(SiMe3)2] (Ia), which isomerizes to the trans-isomer (Ib) upon warming to 0 °C; the structure of Ib was determined by X-ray diffraction studies. Complex Ib reacts with Pt(PEt3)2Cl2 in the presence of 3 equiv of sodium benzophenone to generate the bridging, dinuclear η1,η2-cyaphide complex Cl(Et3P)2Pt(μ-η1,η2-C⋮P)Pt(PEt3)2 (II) in good yield, providing a much simpler and higher yield preparation of II, which was synthesized and characterized previously by a more circuitous route. Compound II reacts with 0.5 equiv of [Cl2Pt(PEt3)]2 or with 1 equiv of W(CO)5(THF) to generate the trinuclear metal−cyaphide complexes Cl(Et3P)2Pt[μ-η1,η1,η2-C⋮P{Pt(PEt3)(Cl)2}]Pt(PEt3)2 (III) and Cl(Et3P)2Pt[μ-η1,η1,η2-C⋮P{W(CO)5}]Pt(PEt3)2 (IV), respectively, in which the lone pair of electrons on the C⋮P phosphorus atom is coordinated to a Pt(PEt3)(Cl)2 fragment in the former and ...
Control of a Jet Using Circumferential Discrete Perturbations

ABSTRACT Effects of discrete perturbations around the exit perimeter of a jet were studied. Visualization and velocity results were obtained. The initial effect of the perturbations is a circumferential wrinkling of the jet. The wrinkle subsequently evolves into a ring of horse-shoe vortices, with the number of vortices corresponds with the number of perturbations. Farther downstream additional vortices were induced, resulting in multiple layers of three-dimensional vortices around the jet circumference. The spread of a jet can be suppressed or enhanced depending on the distribution of perturbations. With appropriate perturbations the velocity fluctuation level during initial development can be reduced significantly in comparison with an axi-symmetric jet. At several diameters downstream a sudden transformation can be observed in the controlled jet. During the transformation the mean velocity and rms level will change abruptly over a short axial distance, and the flow behaviors become similar to that of an axi-symmetric jet.
THE GENUS MEGALOXANTHA NEW TO CHINA WITH TWO NEW SPECIES (COLEOPTERA: BUPRESTIDAE)

The buprestid genus Megaloxantha Kerremans, with mostly beautiful and gigantic members, has been revised by Y. Kurosawa (1978) and has 15 species and subspecies in world fauna. It is widely distributed in the tropical rainforest regions of India, Indochina, Malay Peninsula, Borneo, Sumatra, Java and the Philippines, but there is yet no record from China. The present, paper reports two new species collected from Guizhou and Hainan, and they are described as follows.1.Megaloxantha luodiana Yang et Xie, sp. nov. (fig. 1)Holotype , Guizhou Province: Luodian Co. (106.7E, 25.4N), 400 m, V -1956, collected by Liu Jingwen, depasited in the Insect Collection of Beijing Agricultural University. Paratype 1 (broken), same as the holotype, kept in the Institute of Plant Protection, Guizhou Academy of Agricultural Sciences.Body length 71.5 mm, width 21.5 mm. Head and pronotum bluish black, with a large brown tubercle at the posterior angles of pronotum. Elytra metallic green, subparallel, the yellow markings small and oblique. Legs bluish black. Body beneath brownish ivory, head, lateral margin of prosternal process and pleura of pro-and meso-thorax bluish black. Metasternum with a subtriangular black marking above the transverse suture. Allied to M. bicolor (FabriciusX but differs from it by the colour of head and thorax, the markings of pronotum and elytra also very different. Especially the black markings on the body beneath can separate it from all the other species of this genus.2.Megaloxantha hainana Yang et Xie, sp. nov. (figs. 2, 3)Holotype ,Hainan Province: Danxian Co. (Nada) (109.5E, 19.5N), VI -1974, collected by Ping Zhengming, deposited in the Entomological Museum, Northwestern Agricultural University, Yangling, Shaanxi.Body length 61.0 mm, width 22.5 mm. Head bluish black, front before the V-shape suture and around the eyes metallic blue. Pronotum dark blue, shining, with a very large yellowish brown tubercle at the posterior angles of pronotum. Elytra golden green with bronzy shining, dilated posteriorly, about 2.2 times as long as wide, the yellow markings large and around with irregular blue margin. Legs bluish black. Body beneath yellowish ivory, the bluish black parts and the black marking of metasternum like the above species. This new species with elytra broadened posteriorly somewhat similar to M. netscheri (Lansberg), but easily distinguishable from it by the pronotum, the latter without any tubercle at the posterior angles, and belonging to a different species-group.
Defining infection in chronic wounds: does it matter?

A discussion highlighting the importance of establishing the bacterial balance within chronic wounds
Cardiovascular health in adults with type 1 diabetes

Abstract Adults with type 1 diabetes (T1D) are at risk for cardiovascular (CV) disease. Managing CV risk is an important prevention strategy. The American Heart Association has defined 7 factors for ideal CV health. The purpose of this 2016 secondary analysis was to assess the prevalence of 6 CV health factors in a sample of adults ≥ 18 (n = 7153) in the T1D Exchange Clinic registry. CV health factors include: hemoglobin A1c (HbA1c) The mean age was 37.14 ± 17 years. Mean HbA1c was 7.9 ± 1.5%, and duration was 19.5 ± 13.5 years. The majority (54%) were working full or part-time. Achievement of CV health factors in the whole sample ranged from 27% (HbA1c This young sample exhibited low levels of some CV health factors, especially HbA1c and physical activity. Providers need to routinely assess and advise on management of all CV risk factors to prevent this common diabetes complication.
Relationship between Interdialytic Weight Gain and Blood Pressure in Pediatric Patients on Chronic Hemodialysis

Overhydration is reported to be the main cause of hypertension (HTN) as well as to have no association with HTN in hemodialysis (HD) population. This is the first report of the relationship between interdialytic weight gain (IDWG) and pre-HD blood pressure (BP) in pediatric patients in relation to residual urine output (RUO). We studied 170 HD sessions and interdialytic periods performed during a 12-week period in 5 patients [age 4–17 years, weight 20.8–66 kg, 3 anuric (102 HD sessions), and 2 nonanuric (68 HD sessions)]. BP is presented as systolic BP index (SBPI) and diastolic BP index (DBPI), calculated as systolic or diastolic BP/95th percentile for age, height, and gender. IDWG did not differ () between anuric and nonanuric pts. There was a positive but not significant correlation between IDWG and both pre-HD SBPI (, ) and pre-HD DBPI (, ). Pre-HD SBPI ( versus ) and DBPI ( versus ) were higher in nonanuric patents ( and , resp.). Pre-HD HTN may not be solely related to IDWG and therapies beyond fluid removal may be needed. Individualized approach to HTN management is necessary in pediatric dialysis population.
Quantitative electromyography in ambulatory boys with Duchenne muscular dystrophy.

Introduction This study's objective was to evaluate quantitative electromyography (QEMG) using multiple-motor-unit (multi-MUP) analysis in Duchenne muscular dystrophy (DMD). Methods Ambulatory DMD boys, aged 5–15 years, were evaluated with QEMG at 6-month intervals over 14 months. EMG was performed in the right biceps brachii (BB) and tibialis anterior (TA) muscles. Normative QEMG data were obtained from age-matched healthy boys. Wilcoxon signed-rank tests were performed. Results Eighteen DMD subjects were enrolled, with a median age of 7 (interquartile range 7–10) years. Six-month evaluations were performed on 14 subjects. QEMG showed significantly abnormal mean MUP duration in BB and TA muscles, with no significant change over 6 months. Conclusions QEMG is a sensitive electrophysiological marker of myopathy in DMD. Preliminary data do not reflect a significant change in MUP parameters over a 6-month interval; long-term follow-up QEMG studies are needed to understand its role as a biomarker for disease progression. Muscle Nerve, 2017
The Scanlon Plan: A Need for Conceptual and Empirical Models

Since its inception, the Scanlon Plan has attracted considerable attention. The current national concern with productivity has renewed interest in the Plan as a way to improve productivity levels as well as the quality of work. The attractive features of the Plan include a phi1osopy based on cooperative labor-management relationships, a structure for increasing productivity, and an opportunity for increased need satisfaction for all employees. Despite the many benefits attributed to the Plan, it is the position of this paper that: (1) there have been few well designed studies that can assess the multiple impacts of the Plan, and (2) there has been little theoretical elaboration of models that would aid in predicting , the impact of the Plan in different types of organizations over time. The lack of systematic research and theorizing is not mer'e1y of academic interest; it also has real practical implications.
Altered acrylic acid concentrations in hard and soft corals exposed to deteriorating water conditions

A reliable marker of early coral response to environmental stressors can help guide decision-making to mitigate global coral reef decline by detecting problems before the development of clinically observable disease. We document the accumulation of acrylic acid in two divergent coral taxa, stony small polyp coral (Acropora sp.) and soft coral (Lobophytum sp.), in response to deteriorating water quality characterized by moderately increased ammonia (0.25 ppm) and phosphate (0.15 ppm) concentrations and decreased calcium (360 ppm) concentration, using nuclear magnetic resonance spectroscopy (NMR)-based metabolomic techniques. Changes in acrylic acid concentration in polyp tissues free of zooxanthellae suggest that acrylic acid could be a product of animal metabolism and not exclusively a metabolic by-product of the osmolyte dimethylsulfoniopropionate (DMSP) in marine algae or bacteria. Our findings build on previously documented depletions of acrylic acid in wild coral potentially correlated to temperature ...
Acquired Genomic Copy Number Aberrations in CLL

Approximately 80 % of chronic lymphocytic leukemia (CLL) carries somatically acquired genomic copy number aberrations (aCNAs). These include gains of entire chromosomes (trisomy 12) and recurrent genomic losses, including interstitial deletions of various lengths at 13q14, 11q, and of more uniform length at 17p. In addition, approximately 10–15 second-tier aCNAs, with frequencies of 1–5 %, have been identified. In this chapter, we will discuss the biology and clinical significance of these CLL-associated aCNAs in detail and also discuss generic aspects of aCNAs relevant to all cancer cells. The hypothesis is advanced that most if not all aCNAs in CLL deregulate multiple target genes as a consequence of aCNA-associated gene mutations and through stable deregulation of gene expression. The concept of elevated genomic complexity (multiple aCNAs per CLL case) is reinforced as one of the strongest biological traits associated with aggressive CLL with short survival. Further, all inherited polymorphic copy number variations as detected through SNP 6.0 array profiling of T-cell-derived DNA of 255 CLL patients are listed to allow the reader a more critical appraisal of the somatic status of CLL-associated aCNAs as reported in the literature. Finally, given that aCNAs and gene mutations coexist in many CLL cells, we stress the importance of understanding in detail the relative biological and clinical roles each mutation type serves in individual CLL patients; this is a research area in need of more in-depth investigation.
Lancet Commission on Global Surgery

: Nearly a third of the global burden of disease require availability of surgical and anesthetic services. However, five billion people currently lack access to safe, affordable surgical and anesthesia care. Each year, appendicitis, hernia, open fracture and other common, treatable surgical diseases result in millions of disabilities and deaths. This is in part due to lack of political will, financial resource allocation, and relevant policy measures. To address these glaring needs, the lancet commission on global surgery (LCoGS) was formed to identify the barriers to access of surgical and anesthesia care, and the current state of these services worldwide. Additionally, its purpose was to identify opportunities for improvement and development to provide safe surgery in low-income and middle-income settings. To address the needs of surgical and anesthesia services LCoGS created 5 key messages, a set of 6 core surgical system indicators, and a health system strengthening framework for national surgical care planning. These key outputs of the commission highlighted that a widespread expansion of surgical care improves overall health and welfare of populations and improved economic returns. The findings were published as a report in the spring of 2015 to facilitate increased surgical care access that was safe, affordable, and cost-effective particularly for low-income and middle-income countries. In this review article, we summarize this seminal report and ldquo; global surgery 2030: evidence and solutions for achieving health, welfare, and economic development and rdquo; published in the Lancet 2015.
Adolescent fathers: what we know and what we need to know.

Research into adolescent parenting involvement has focused primarily on mothers while neglecting fathers. This article concentrates on factors that influence the parental involvement of adolescent fathers. These factors must be acknowledged and addressed by practitioners working with adolescent parents. Issues relevant to the parental involvement of African-American adolescent fathers are highlighted in order to balance the negative portrayal this particular group continues to experience. Implications and suggestions for social work practitioners, policy makers, and social researchers are also discussed.
Assessing Language Revitalization: Methods and Priorities

With the rapid growth of interest in language revitalization and the development of hundreds of programs around the world, there is now a recognized need for ways to assess progress and identify problems. The primary objectives of this review are to outline the form that assessments of oral proficiency can take and to illustrate ways in which revitalization programs can begin to monitor their progress, by means of a combination of holistic appraisals of fluency and techniques that target individual features of language.
A review of slip transfer: applications of mesoscale techniques

In this review article, we present and discuss recent mesoscale modeling studies of slip transmission of dislocations through biphase interfaces. Specific focus is given to fcc/fcc material systems. We first briefly review experimental, atomistic, and continuum-scale work that has helped to shape our understanding of these systems. Then several mesoscale methods are discussed, including Peierls–Nabarro models, discrete dislocation dynamics models, and phase field-based techniques. Recent extensions to the mesoscale mechanics technique called phase field dislocation dynamics are reviewed in detail. Results are compiled and discussed in terms of the proposed guidelines that relate composite properties to the critical stress required for a slip transmission event.
Logic and Set Theory

This chapter presents some of the fundamental ideas of logic and set theory and establishes the notation that is to be used subsequently. “Statement” means a declarative, meaningful sentence or phrase in grammatically correct English, which is capable of having assigned to it one truth value, true (T) or false (F). Closely related to the concept of statement is that of an open sentence, or statement function. It means a collection of words and symbols, the latter called variables, which becomes a statement when each variable is replaced by a certain object. Some symbols stand for variables and others do not. In addition to the device of substituting specific items for variables, there is another way to make statements from open sentences; this process is called quantification. The chapter discusses two prefix-like symbols, called quantifiers: the universal quantifier, and the existential quantifier. There is a treatment of set theory in which sets are defined in terms of more primitive things.
The Case for Performance Studies in Undergraduate Music History Teaching

As a broadly defined scholarly (inter)discipline, performance studies draws on theater studies, anthropology, gender and queer studies, race studies, poststructuralism, and postcolonial theories. Although taught mostly at the graduate level, performance studies can offer undergraduates an inroad into critical thinking through the relatable and widely applicable lens of performance. In the following article, I argue for the inclusion of performance studies in Western art music history pedagogy, discussing my experience designing and leading an introductory performance studies course for music majors. I argue that integrating such a course into a music curriculum is beneficial for students with various music concentrations, and I also suggest strategies for incorporating main concepts and activities into more traditional music history courses. The vibrant and interdisciplinary field of performance studies is flexible in terms of content and may be easily tailored to fit the needs of music majors while expanding their intellectual horizons and developing their critical thinking skills.
Adhesion receptor expression by hematopoietic cell lines and murine progenitors: modulation by cytokines and cell cycle status.

Abstract Hematopoietic progenitor cells are incubated with cytokine combinations for in vitro expansion of stem cells and to enhance retrovirus-mediated gene transfer. Optimization of the engraftment of these treated cells would be critical to the success of stem cell transplantation or gene therapy. Previous studies demonstrated that a 48-hour incubation of donor BALB/c bone marrow with a mixture of four cytokines (IL-3, IL-6, IL-11, and SCF), resulted in expansion of primitive progenitor/stem cells but a loss of long-term engraftment in nonmyeloablated or myeloablated recipients. We have established the expression pattern for a number of adhesion receptors by normal hematopoietic progenitors and cell lines and the modulation in expression induced by cytokines or cell cycle progression to ascertain the molecular basis for such defective engraftment. Northern blot analysis demonstrated that the cytokine combination of IL-3, IL-6, IL-11, and SCF dramatically downregulated α 4 integrin receptor expression in HL-60 cells. Synchronized FDC-P1 cells exhibited modulation of α 4 expression through cell cycle progression, both by quantitative RT-PCR and flow cytometry. Normal murine bone marrow lineage-depleted, Sca + cells expressed a number of adhesion receptors, including α L , α 1 , α 3 , α 4 , α 5 , α 6 , β 1 , L-selectin, CD44, and PECAM as assessed by flow cytometry, immunofluorescence, and RT-PCR. There was modulation of the expression of several of these receptors after incubation in the four cytokines for 24 and/or 48 hours: the proportion of cells expressing α L , α 5 , α 6 , and PECAM increased, whereas the proportion of cells expressing α 4 and β 1 decreased, after cytokine incubation. There was a demonstrable concomitant decline in adhesion of these cells to fibronectin after the cytokine incubation, a finding that correlates with the decrease in expression of α 4 . These changes in adhesion receptor expression and function with cytokines and during cell cycle transit may be critical to stem cell homing and engraftment after transplantation, as multiple receptors could be involved in the process of rolling, attachment to endothelium, endothelial transmigration, and migration within the marrow space.
Psychologically informed physical fitness practice in schools: A field experiment

Abstract Objectives Physical education could play a role in attenuating the decline in physical activity during the childhood-to-adolescence transition and inspiring children to adopt a lifelong physical activity habit. While psychological theories (e.g., Self-Determination Theory, Achievement Goal Theory) offer pointers for desirable changes to practice norms, experimental tests of the effectiveness of theory-based interventions in school settings are lacking. In this study, we compared the effects of a "traditional" and a "novel" physical education lesson on affective valence, enjoyment, and perceived satisfaction of the psychological needs for autonomy, competence, and relatedness. Design Within-subjects field experiment, with two counterbalanced conditions. Method The participants were 148 children (4-6th grade, 52% female). Both lessons consisted of practicing aerobic capacity (running), core (curl-ups), and upper-body (push-ups) strength and endurance. In the "traditional" lesson, practice procedures followed FITNESSGRAM™ test instructions. The "novel" lesson incorporated elements designed to address basic psychological needs (e.g., freedom to select preferred running path, positive interactions among peers) and other evidence-supported modifications (e.g., music and video). Results Affective valence declined in the "traditional" lesson but remained stable in the "novel" lesson. Enjoyment and need-satisfaction for competence were higher after the "novel" lesson. These differences occurred despite no significant differences in total accelerometer-assessed moderate-to-vigorous physical activity and the intensity of the aerobic components. Conclusions Easily implementable, theory-based modifications to physical education practices could improve the experiences derived by students. In turn, experiencing physical education as more pleasant, enjoyable, and need-supportive could raise the odds of long-term physical activity participation.
Treatment-Induced Tumor Cell Apoptosis and Secondary Necrosis Drive Tumor Progression in the Residual Tumor Microenvironment through MerTK and IDO1

Efferocytosis is the process by which apoptotic cells are cleared from tissue by phagocytic cells. The removal of apoptotic cells prevents them from undergoing secondary necrosis and releasing their inflammation-inducing intracellular contents. Efferocytosis also limits tissue damage by increasing immunosuppressive cytokines and leukocytes and maintains tissue homeostasis by promoting tolerance to antigens derived from apoptotic cells. Thus, tumor cell efferocytosis following cytotoxic cancer treatment could impart tolerance to tumor cells evading treatment-induced apoptosis with deleterious consequences in tumor residual disease. We report here that efferocytosis cleared apoptotic tumor cells in residual disease of lapatinib-treated HER2+ mammary tumors in MMTV-Neu mice, increased immunosuppressive cytokines, myeloid-derived suppressor cells (MDSC), and regulatory T cells (Treg). Blockade of efferocytosis induced secondary necrosis of apoptotic cells, but failed to prevent increased tumor MDSCs, Treg, and immunosuppressive cytokines. We found that efferocytosis stimulated expression of IFN-γ, which stimulated the expression of indoleamine-2,3-dioxegenase (IDO) 1, an immune regulator known for driving maternal-fetal antigen tolerance. Combined inhibition of efferocytosis and IDO1 in tumor residual disease decreased apoptotic cell- and necrotic cell-induced immunosuppressive phenotypes, blocked tumor metastasis, and caused tumor regression in 60% of MMTV-Neu mice. This suggests that apoptotic and necrotic tumor cells, via efferocytosis and IDO1, respectively, promote tumor 'homeostasis' and progression. SIGNIFICANCE: These findings show in a model of HER2+ breast cancer that necrosis secondary to impaired efferocytosis activates IDO1 to drive immunosuppression and tumor progression.
UV fluorescence excitation spectroscopy as a noninvasive predictor of epidermal proliferation and clinical performance of cosmetic formulations

Background The epidermis is the outermost layer of skin and is composed of cells primarily containing keratin. It consists of about ten layers of living cells (keratinocytes) and ten layers of dead cells (corneocytes). Thinning of the epidermis and decreased proliferation of its cells are associated with aging related changes in skin, including wrinkling and laxity. Fluorescence excitation spectroscopy is a noninvasive method of monitoring characteristic excitation-emission peaks in skin that have been related to the epidermal and dermal composition. The magnitude of the peak that occurs at 295nm excitation (F295) has been linked to changes in epidermal thickness, proliferation, and skin aging. Aim The goal of this study is to correlate changes in the F295 signal with proliferation of cells and thickening of the epidermis induced by cosmetic formulations. We hypothesize that two commonly used cosmetic ingredients, retinol and glycolic acid, will increase these markers that have been implicated in skin anti-aging. Methods In a placebo-controlled study subjects' forearms were treated with formulations containing retinol or glycolic acid under occlusive patch for a period of 21 days. Skin fluorescence was measured at baseline and after treatment, and biopsies were taken following treatment for histological analysis of epidermal thickness and cell proliferation. Results After 21 days of treatment retinol and glycolic acid formulas significantly increased F295 (by 265.1±33.5% and 162.2±18.7% respectively), whereas the placebo control formula did not induce a change from baseline. Furthermore, retinol and glycolic acid treatments significantly increased epidermal thickness (by 63.1% and 7.8% respectively) and keratinocyte proliferation (by 236.9% and 62.8% respectively) versus placebo control. Conclusion Increases in F295 were found to correlate with epidermal renewal, but more so with increased cell proliferation than epidermal thickness. We conclude that the F295 signal is a fast and reliable early indicator of epidermal remodeling in skin that can be used to distinguish between formulations with different cosmetic ingredients.
Two Contrasting African Easterly Wave Behaviors

AbstractThe dominant structural variability of African easterly waves (AEWs) is explored using an empirical orthogonal function (EOF) approach. The structure of AEWs is obtained by projecting the w...
A stochastic planning framework for the discovery of complementary, agricultural systems

Abstract One of the greatest 21st century challenges is meeting the need to feed a growing world population which is expected to increase by about 35% by 2050. To meet this challenge, it is necessary to make major improvements on current food production and distribution systems capabilities, as well as to adapt these systems to expected trends such as climate change. Changing climate patterns may present opportunities for unidentified, geographical regions with adequate climate patterns to produce high-value agricultural products in a profitable and sustainable manner. This paper focuses on the design and planning aspects of a discovery process to unearth agri-food supply chains capable of generating attractive return on investments. A stochastic optimization framework is used to develop planting and harvesting schedules for a set of identified regions with complementary weather characteristics. To address the high-level of variability in the problem context, a two-stage stochastic decomposition method is used to consider a larger number of scenarios. As part of the solution process, a modeling scheme is developed that learns past interactions between entering discretized, weather scenarios and optimal first-stage solutions. In this context, machine learning and dimensionality reduction techniques are used to iteratively estimate each region's probability of belonging to first-stage solutions based on previous solution-scenario results. The implementation of the stochastic framework is shown through a case study applied to multiple locations within the US southwest states of Arizona and New Mexico.
Experimental Visualization of Hybrid Combustion: Results at Elevated Pressures

This work was undertaken in an effort to improve the understanding of the combustion processes inside classical and fast-burning hybrid rocket motors. In this paper, a combustion visualization expe...
Medically Complex Dental Implant Patients: Controversies About Systemic Disease and Dental Implant Success/Survival

Advances in dental implant therapy have created choices to enhance the expectations of dental practitioners and their patients with respect to oral rehabilitation at any age after childhood and regardless of, in most cases, medical disabilities. The medical status of the patient however can significantly influence the success rate of dental implant therapy. This article applies the hierarchy of scientific evidence ranging from case reports, retrospective, prospective cohort investigations, systematic reviews, and meta-analyses criteria in order to determine whether dental implant placement in medically compromised patients yields any detrimental sequelae.
An Integrated Approach to Selecting a Prepared Medical Decision-Maker

Abstract Background We implemented a systematic multidisciplinary process to engage new outpatients with cancer in selecting and preparing a medical decision-maker. Measures Templated advance care planning notes and medical power of attorney documents were used in the electronic health record by the third office visit. Intervention Patients were coached to meet with social work from a “culture of yes,” viewed a video about the importance of selecting a prepared medical a decision-maker in English or in Spanish, and referenced cards containing simple explanations of advance directives when responding to advance directive questions. Outcomes A total of 351 patients were evaluated. By visit 3, there was no increase in documented social work advance care planning notes in intervention or scanned medical power of attorney documents in the electronic health record. Conclusions/Lessons Learned This systematic multidisciplinary approach did not engage new outpatients with cancer in preparing a medical decision-maker. More active physician involvement and varied ways of engagement are needed.
Synergy of Anaerobic Soil Disinfestation and Trichoderma spp. in Rhizoctonia Root Rot Suppression

Potential synergy between anaerobic soil disinfestation (ASD) and Trichoderma spp. in suppression of Rhizoctonia root rot in radish was evaluated. A split-plot design with three replications was used; main plots were T. harzianum T22, T. asperellum NT25 and a non-Trichoderma control. Subplots were ASD carbon sources wheat bran, molasses, chicken manure, and mustard greens and two non-amended controls: anaerobic (covered and flooded) and aerobic (not covered or flooded). Carbon sources and R. solani inoculant were mixed with soil, placed in pots and flooded, followed by drenching Trichoderma spore suspensions and sealing the pots in zip-lock bags. After three weeks, bags were removed, soil was aired for one week and radish 'SSR-RR-27' was seeded. Rhizoctonia root rot severity and incidence were lowest in radish plants grown in ASD-treated soil amended with wheat bran, molasses or mustard greens across all Trichoderma treatments. Disease severity was lower in radish plants treated with NT25 than with T22 or the non-Trichoderma control across all ASD treatments, and in radish grown in ASD-treated soil amended with wheat bran plus NT25 compared to ASD-wheat bran or NT25 alone. Rhizoctonia solani populations were significantly reduced by ASD treatment regardless of carbon source, while Trichoderma populations were not affected by ASD treatment with the exception of ASD-mustard greens. The interactions of either Trichoderma isolate and ASD with most carbon sources were additive, while T22 with ASD-molasses and NT25 with ASD-wheat bran interactions were synergistic in reducing disease severity. One interaction, T22 with ASD-chicken manure was antagonistic. Enhancement of ASD efficacy in suppressing soilborne diseases such as Rhizoctonia root rot by additional soil amendment with Trichoderma spp. during the process appears to be dependent on both Trichoderma isolate and ASD carbon source.
On Topological Entropy of Interconnected Nonlinear Systems

We study topological entropy of a nonlinear system represented as an interconnection of smaller subsystems. Under suitable assumptions on the Jacobian matrices characterizing the interconnection, we obtain an explicit upper bound on the entropy of the overall system, and show that it can be related to upper bounds on the entropies of the subsystems. We also analyze in detail the special case of a cascade connection of two subsystems, establishing an upper bound on the entropy which is more tightly linked to individual entropy bounds for the subsystems.
Otolaryngology Resident Education and Perceptions of e-cigarettes.

Objective:To date, there are no reports of otolaryngology residents’ knowledge and confidence in discussing e-cigarette use. The purpose of this study was to evaluate otolaryngology resident e-ciga...
A Global Expeditionary PLA: 2025-2030

This chapter considers the doctrinal, strategic and force posture changes the PLA may undergo to become a global expeditionary force by 2025-2030 and assesses the implications of these changes for Chinese propensity to use force and regional and global stability.
Aromatase inhibitor-induced inflammatory myopathies: A case series.

Abstract Objective: Aromatase inhibitors (AIs) are widely used in the adjuvant therapy setting in patients with estrogen receptor–positive breast cancer. Rheumatic side effects of AIs have been reported, including bone loss, arthralgias, myalgias, and tenosynovitis. There is emerging evidence that AIs are linked to new-onset autoimmune diseases. Here, we describe three novel cases of inflammatory myopathies that occurred during AI therapy. Methods: In total, three patients with inflammatory myopathy in the setting of AI therapy were treated in the Section of Rheumatology, MD Anderson Cancer Center. All the patients were retrospectively chart reviewed. We obtained verbal consent from the patients for use of their cases for teaching and publication purposes and only de-identified data have been used. Results: None of our patients from these three cases had a history of autoimmune disease and all had undergone recent cancer screenings, indicating no re-occurrence of breast cancer and no evidence of new cancer. The completion or discontinuation of AI therapy was associated with the resolution of the myopathies in all three cases. Conclusions: This case series suggests a link between AIs and the new onset of inflammatory myopathy. If a patient develops an inflammatory myopathy while on an AI, the AI therapy should be considered the possible trigger. If the myopathy cannot be controlled with immunosuppression, then discontinuation of the AI should be considered.
Factors associated with time to initiation of a PCSK9 inhibitor after hospital discharge for acute myocardial infarction.

Background Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) lower atherosclerotic cardiovascular disease (ASCVD) event risk. Objective Analyze patient characteristics associated with time to PCSK9i initiation following an acute myocardial infarction (AMI). Methods We analyzed characteristics of patients ≥21 years of age in the Marketscan or Medicare databases who initiated a PCSK9i 0-89 days, 90-179 days, or 180-365 days after an AMI between July 2015 and December 2018 (n=1,705). We estimated the cumulative incidence of recurrent ASCVD events before PCSK9i initiation. Results Overall, 42%, 25%, and 33% of patients who initiated a PCSK9i did so 0-89 days, 90-179 days, and 180-365 days following AMI hospital discharge, respectively. Taking ezetimibe prior to AMI hospitalization and initiating ezetimibe within 30 days after AMI hospital discharge were each associated with a higher likelihood of PCSK9i initiation in the 0-89 days versus 180-365 days post-discharge (adjusted odds ratio [OR] 1.83, 95% confidence interval [95%CI] 1.35-2.49 and 1.76, 95%CI 1.11-2.80, respectively). Statin use before and statin initiation within 30 days after AMI hospitalization were associated with a lower likelihood of PCSK9i initiation 0-89 days versus 180-365 days post-discharge (adjusted OR 0.64, 95%CI 0.49-0.84 and 0.39, 95%CI 0.28-0.54, respectively). Overall, 8.0%, 10.5%, and 12.5% of patients had an ASCVD event at 90, 180, and 365 days following AMI hospital discharge and before initiating a PCSK9i, respectively. Conclusion Among patients initiating a PCSK9i after AMI, a low proportion did so within 89 days of hospital discharge. Many patients had a recurrent ASCVD event before treatment initiation.
Development of a synthetic pathway to convert glucose to hydrogen using cell free extracts

Abstract Sustainable production of biochemicals from cellulosic biomass is an attractive alternative to chemical production from fossil fuels. We describe the further development of a three protein synthetic pathway to convert NADPH and H + to hydrogen using a ferredoxin-NADP + reductase, a ferredoxin, and the [FeFe] hydrogenase from Clostridium pasteurianum at a rate greater than 14 mmol H 2 L −1 hr −1 using natural enzymes. We also demonstrate the feasibility of coupling this pathway to a cell-free extract to convert glucose to hydrogen in a potentially cost effective manner. Both of these accomplishments serve as the basis for further engineering to optimize both the yield and productivity of a low-cost cell-free process for the production of highly reduced biochemicals.
Effect of serotonin on water and electrolyte transport in the in vivo rabbit small intestine.

The influence of intravenously administered serotonin on water and electrolyte fluxes in the in vivo rabbit jejunum and ileum was examined. Animals were divided into four groups: (1) those receiving saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) serotonin given intravenously while glucose-free intestinal perfusate was used as in group I; (3) intravenous saline given while a 10 mM glucose-isotonic saline solution perfused the jejunum and ileum; and (4) intravenous serotonin given while the intestinal perfusate was as in group 3. Serotonin administration resulted in highly significant net secretion of H2O and sodium in both jejunum and ileum in the groups with a glucose-free perfusate. In jejunum, serotonin evoked net water and sodium secretion. whereas controls absorbed water and sodium. In ileum. serotonin significantly enhanced secretion. The addition of glucose to the perfusate completely abolished the serotonin effect. Unidirectional 22Na flux analysis revealed a marked diminution in both mucosal to serosal and serosal to mucosal fluxes in serotonintreated animals. The decrease in mucosal to serosal flux was greater than the decrease in serosal to mucosal flux. thus explaining the enhanced net secretion observed with serotonin in the groups receiving glucose-free perfusate. In spite of its pronounced effect on water and electrolyte transport. serotonin failed to produce any detectable histological alterations in small bowel mucosa. either by light or electron microscopy. We postulate that serotonin may be an important mediator of the diarrhea so frequently noted in the carcinoid syndrome by virtue of its effects on small intestinal H2O and electrolyte transport.
Trajectory and Model Studies of Collisions of Highly Excited Methane with Water Using an ab Initio Potential.

Quasi-classical trajectory studies have been performed for the collision of internally excited methane with water using an accurate methane–water potential based on a full-dimensional, permutationally invariant analytical representation of energies calculated at a high level of theory. The results suggest that most energy transfer takes place at impact parameters smaller than about 8 Bohr; collisions at higher impact parameters are mostly elastic. Overall, energy transfer is fairly facile, with values for ⟨ΔEdown⟩ and ⟨ΔEup⟩ approaching almost 2% of the total excitation energy. A classical model previously developed for the collision of internally excited molecules with atoms (Houston, P. L.; Conte, R.; Bowman, J. M. J. Phys. Chem. A 2015, 119, 4695–4710) has been extended to cover collisions of internally excited molecules with other molecules. For high initial rotational levels, the agreement with the trajectory results is quite good (R2 ≈ 0.9), whereas for low initial rotational levels it is only fair ...