cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeted Therapy of Colorectal Cancer: Clinical Experience with Bevacizumab

Advanced colorectal cancer remains an urgent health concern, despite improvements in systemic chemotherapy. Targeted therapeutics promise effective tumor therapy with minimal side effects. Angiogenesis (the formation of new blood vessels) is essential for tumor growth and metastasis and may be an ideal target in the search for new antineoplastic agents. Vascular endothelial growth factor is one of the best characterized of the proangiogenic growth factors that regulate angiogenesis and is a logical target in colorectal cancer therapy. Bevacizumab (Avastin; Genentech Inc.; South San Francisco, CA), a humanized murine monoclonal antibody directed at vascular endothelial growth factor, is being evaluated in the treatment of various types of cancer. It has shown promising efficacy in phase II clinical trials in patients with metastatic colorectal cancer. Addition of bevacizumab at a dose of 5 mg/kg to chemotherapy (5-fluorouracil plus leucovorin) resulted in a higher objective response rate (40% versus 17%), longer time to disease progression (9.0 versus 5.2 months), and longer median survival time (21.5 versus 13.8 months). Hypertension and thrombosis were the principal safety concerns, but were manageable. Further phase II/III studies of bevacizumab, administered with 5-fluorouracil plus leucovorin, with or without irinotecan and/or oxaliplatin, in colorectal cancer, are under way.
The Arithmetic of Entire Functions under Composition

In this paper, we prove, among other things, that any family of nonconstant entire functions of one complex variable has a greatest common right factor under composition. We prove a corresponding result for any family of pairwise dependent entire functions of N complex variables. Since f and af +b, where a, b # C and a{0 have all the same properties from the point of view of factoring under composition, we once and for all identify them, but continue (perhaps a little improperly) to talk about the equivalence classes as ``functions.'' Moreover we identify f and f b A where A is a biholomorphic one-to-one map of C onto C. Here are some definitions. Let f = f (z1 , ..., zn) be a nonconstant entire function of N complex variables, and let g= g(w) be a nonconstant holomorphic function in the region consisting of the complex plane minus any possible value omitted by f. Then the composition h=g b f, h(z1 , ..., zN)=g( f (z1 , ..., zN)) is a welldefined entire function, and in this case we call f a right factor of h. If we have a family of the form [h:]=[ g: b f ], then we say that f is common right factor of [h:]. If we have h=g: b f: , where : runs over an index set A, then we call h a common left multiple of the f: . For entire functions f and g of N complex variables, define f g if f (z)= f (w) implies g(z)=g(w), z, w # C. Then we remark that f g if and only if f is a right factor of g. The ``if '' part is trivial. For the ``only article no. 0087
CARMA(p,q) generalized random processes

Abstract There is now a vast literature on the theory and applications of generalized random processes, pioneered by Ito (1953) , Gel’fand (1955) and Yaglom (1957) . In this note we make use of the theory of generalized random processes as defined in the book of Gel’fand and Vilenkin (1964) to extend the definition of continuous-time ARMA(p,q) processes to allow q ≥ p , in which case the processes do not exist in the classical sense. The resulting CARMA generalized random processes provide a framework within which it is possible to study derivatives of CARMA processes of arbitrarily high order.
Development and validation of a fixed-precision sequential sampling plan for estimating brood adult density of Dendroctonus pseudotsugae (Coleoptera: Scolytidae).

The Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins, attacks Douglas-fir, Pseudotsuga menziesii (Mirb.) Franco (Pinaceae), throughout western North America. Periodic outbreaks cause increased mortality of its host. Land managers and forest health specialists often need to determine population trends of this insect. Bark samples were obtained from 326 trees distributed over 21 stands during a 2- year period in late winter to early spring of 1997 and 1998 in the Colorado Front Range. The variance to mean relationship of brood adults was examined using the Taylor power law, and a fixed-precision sampling plan was developed using Green's method. Stop lines and minimum number of samples required to estimate brood adult density per 0.046 m2 with precision levels of 0.1, 0.2, and 0.3 were calculated. A resampling simulation conducted with an independent data set indicated that desired precision levels were not met. Theoretical precision levels were adjusted until desired precision levels were achieved. Average number of samples needed to estimate brood adult densities up to 25.1 adults per 0.046 m2 with precision levels of 0.09, 0.2, and 0.3 were 91, 20, and 8, respectively. For densities greater than 25.1 brood adults per 0.046 m2, conservative estimates are obtained with 72, 15, and 6 samples for precision levels of 0.09, 0.2, and 0.3, respectively. An emergence ratio can be obtained by dividing the estimated density of brood adults by twice the number of gallery starts. This system provides the user with an immediate assessment of the population trend of Douglas-fir beetle. The data collected compare favorably with data from other Douglas-fir beetle outbreaks reported in the literature. The use of this plan outside the Colorado Front Range, or by sampling at a different height, should be cautioned until additional data from other locations and sampling heights are examined.
Prisoner's Dilemma as a Model for Understanding Decisions

Two classroom demonstrations based on the prisoner's dilemma illustrate some elements of decision making. The demonstrations require minimal preparation and allow all members of the class to participate. In the first demonstrations, students ask for $1. 00 or $.10, with the condition that, if more than 20% of the class asks for $1.00, no one gets anything. In the second demonstration, pairs of students play a short matching game. The scores earned by students reflect whether they have played cooperatively or competitively.
Spontaneous Erythromycin Resistance Mutation in a 23S rRNA Gene, rrlA, of the Extreme Thermophile Thermus thermophilus IB-21

Spontaneous, erythromycin-resistant mutants of Thermus thermophilus IB-21 were isolated and found to carry the mutation A2058G in one of two 23S rRNA operons. The heterozygosity of these mutants indicates that A2058G confers a dominant or codominant phenotype in this organism. This mutation provides a valuable tool for the genetic manipulation of the 23S rRNA genes of Thermus.
Understanding defect distributions in polythiophenes via comparison of regioregular and regiorandom species

Organic photovoltaics (OPVs) are regarded as promising for solar-electric conversion with steadily improving power conversion efficiencies. For further progress, it is crucial to understand and mitigate defect states (traps) residing in the band-gap of OPV materials. In this work, using capacitancemeasurements, we analyzed two major bands in the density of states (DOS) energy spectra of defects in poly(3-hexylthiophene) (P3HT); regio-regular and regio-random species of P3HT were compared to elucidate the role of morphological disorder. To accurately interpret the obtained DOS profile, trap emission prefactors and activation energy were extracted from temperature dependent capacitance-frequency measurements, while doping, Fermi energy, built-in voltage, and energy levels of the defects were extracted from capacitance-voltage measurements. We identified that the lower energy band—misinterpreted in literature as a defect distribution—stems from free carrier response. The higher energy defect distribution band for regio-random P3HT was an order of magnitude higher than region-regular P3HT, thus stemming from morphological disorder. Impedance spectroscopy was also employed for further comparison of the two P3HT species.
Inflammatory Processes, Febrile Seizures, and Subsequent Epileptogenesis

Febrile seizures (FS) are the most common type of seizures in infants and preschool children. Inflammatory mediators, which are known triggers of fever, have also been implicated as contributors to the onset of these seizures. Evidence that inflammation is present following FS and during established epilepsy suggests that it could also influence epileptogenesis. However, the potential involvement of inflammatory mediators to the epileptogenic process that may follow prolonged FS has yet to be fully determined. This article reviews the current state of our knowledge and major gaps that remain by focusing on four questions: Does inflammation contribute to the generation of FS? Does prolonged FS or febrile status epilepticus (SE) cause temporal lobe epilepsy in the absence of predisposing factors? Does inflammation contribute to the process by which febrile SE causes limbic epilepsy? And finally, can inflammation be a foundation for biomarkers and therapy for FS-induced epileptogenesis?
Gendered Outcomes: Gender Differences in The Biographical Consequences of Activism

This article examines the gendered effects of movement participation on the subsequent lives of activists. We hypothesize that movement participation will have a differential effect on the lives of men and women both because they have different activist experiences by virtue of their gender and because the movements of the New Left questioned the gendered construction of the traditional life course. Using a national random sample, we employ logistic regression and event history models to examine the differences in employment, marriage, and childbirth patterns of men and women who participated in New Left social movements. We hypothesize that New Left activism will have affected the lives of both male and female activists, but that the effect will be stronger for women. The analyses generally confirm this hypothesis. We find significant differences in the influence of social movement participation on the economic, marital, and parenting histories of male and female activists.
Peer Reviewer Agreement for Major Anesthetic Mishaps

In a study of peer reviewer agreement for major anesthetic mishaps, 42 anesthesiologists performed a standardized peer review of 48 reports of anesthetic mishaps obtained from a national data base. The peer review group exhibited agreement (P less than 0.0001) for judgments on the appropriateness of clinical care, the presence or absence of human error, and the role of better monitoring in prevention of the mishap. Personal attributes of the reviewers (eg, type of practice, length of time in practice, and previous experience with mishap review) did not appear to influence agreement. The study findings suggest a highly favorable environment for the development of broadly recognized standards of care in anesthesiology.
Jian'ge 2001～2010 Infectious Pop Characteristics and the Countermeasures to Prevent and Control Analysis

Objective: Through the analysis of the popular trend of statutory infectious disease and three distribution characteristics in 10 years,this paper provides bases for formulating measures and strategies to prevent and control infectious diseases.Methods: Ana-lyzing the popular trend and three distribution by discriptive epidemiological methods.Dealing with the data in statistical analysis through SPSS10.0 and Excel 2003.Results: It was reported 26129 cases of 25 species of b,c class infectious diseases from 2000 to 2010.The annual average incidence rate was 386.89 per 100000 and annual average mortality was 0.15 per 100000.It was blood and sexually trans-mitted infectious diseases and the respiratory infectious disease that accounted for a large proportion of Statutory infectious diseases reports in 10 years.Blood and sexually transmitted infectious diseases rank the first,which were reported 12453 cases of 5 species and accounted for 53.03%.The second was respiratory infectious disease,which was reported 9828 cases of 25 species and accounted for 41.85%.It ranked the first place among all species of infectious diseases in recent 3 years.The third was intestinal infectious disease,reported 1149 cases of 5 species,accounting for 4.89%.The infectious diseases in the top five of incidence rate were hepatitis b,tubercu-losis,mumps,diarrhea and measles,among which hepatitis b and tuberculosis occupied a large proportion.Sexually transmitted infec-tious diseases grow rappidly in recent years.Conclusion: It is blood and sexually transmitted infectious diseases and respiratory infectious disease that are the key infectious diseases for prevention and control.
Spironolactone and hydrochlorothiazide in normal-renin and low-renin essential hypertension

The relative blood pressure response and side effects of spironolactone (S), 400 mg/day, and hydrochlorothiazide (H), 100 mg/day, were evaluated in a double-masked crossed comparison. Subjects were 24 essential hypertensives, 13 normal and 11 with low renin activity. Upright renin levels were determined in the AM after 3 days of moderately low sodium diet (less than 100 mEq/day) and at the end of each drug treatment period. The values were not revealed to one investigator until completion of the study. After 4-week placebo control periods, either S or H was given in divided doses for 6 weeks. Blood pressure measurements and side effects were evaluated at biweekly intervals. The fall in blood pressure from control was the same for each drug and was independent of renin activity. Side effects occurred more often in patients treated with S, and H was judged superior by risk/benefit analysis. We conclude that S is no more beneficial than H in hypertensive patients with either low or normal renin activity but induces a higher incidence of adverse effects in the dose used in this study. We found no evidence for a greater effectiveness of S in low-renin essential hypertension.
Cystic Lung Disease in Down Syndrome: A Case Report and Literature Review

Subpleural lung cysts (SPC) are seen in children with Down syndrome (DS). The incidence and the long term course of these lesions are not known. It is important for pediatricians and pediatric radiologists to be aware of these lung lesions since the DS patients' longevity has increased and they have greater frequency to encounter the clinicians. Autopsy and the radiology series have shown that these lesions are often found in association with congenital heart disease, particularly the endocardial cushion defect and prematurity.
RF substrates yield improvement using package-chip co-design and on-chip calibration

In this paper, yield improvement methodology is proposed for RF substrates with embedded RF passive circuitry. The proposed methodology introduces a concept of package-chip co-design and on-chip calibration of active circuitry for the yield improvement of off-chip passive embedded RF filters. RF receiver architecture for the package-chip co-design and on-chip calibration technique is presented. Using the proposed methodology, it is shown that the yield of RF substrates is improved from 88% to 98%. Also, the measurements results are presented.
The Impact of 1994’s Further Deregulation of the Trucking Industry: The Rural Shippers’ View

This paper focuses on the perceived impact of two legislative changes (elimination of tariffs and intrastate deregulation) affecting the trucking industry that were signed by President Clinton in A...
Three dimensional MHD upper-convected Maxwell nanofluid flow with nonlinear radiative heat flux

Abstract In the present article, three dimensional upper-convected Maxwell (UCM) nanofluid flow over a stretching surface has been considered to examine the effects of nanoparticles and magnetohydrodynamics (MHD) on heat and mass transfer. A nonlinear radiative heat flux is incorporated in the formulation of energy equation. Similarity transformation reduces the nonlinear partial differential equations of the problem to the ordinary differential equations, which are then solved by the well known shooting technique through Runge-Kutta integration procedure of order four. To strengthen the reliability of our results, the MATLAB built-in function bvp4c is also used. Effects of some prominent parameters such as Brownian motion parameter, Prandtl number, thermophoresis parameter, magnetic parameter on velocity, temperature and concentration are discussed graphically and numerically. It is witnessed that flow velocity is diminishing function of linear and nonlinear thermal radiation parameter. Moreover mounting values of Brownian motion parameter lower the nanoparticle concentration profile.
Using video modeling to teach siblings of children with autism how to prompt and reinforce appropriate play

This study investigated the use of video models to teach typically developing children how to prompt and reinforce appropriate play behavior during games with their sibling with autism. With 3 sibling dyads, we extended research on cooperative sibling play by examining video modeling as the sole intervention to facilitate appropriate play between siblings in the absence of specific reinforcement for skills learned in the video model. Video models included brief clips of adults playing games with the child with autism and demonstrating how to prompt and reinforce play behavior. Results indicated that for 2 of the 3 sibling dyads video modeling alone was sufficient to teach prompts and appropriate delivery of reinforcement. An increase in on-task activity engagement was also observed for both siblings with autism across all 3 dyads.
Drivers' smart advisory system improves driving performance at STOP sign intersections

Abstract STOP signs are often physically blocked by obstacles at the corner, forming a safety threat. To enhance the safety at an un-signalized intersection like a STOP sign intersection, a radio frequency identification (RFID) based drivers smart advisory system (DSAS) was developed, which provides drivers with an earlier warning message when they are approaching an un-signalized intersection. In this research, a pilot field test was conducted with the DSAS alarm on an approach towards a STOP sign intersection in a residential area in Houston, Texas. The designed test route covers all turning movements, including left turn, through movement, and right turn. GPS units recorded test drivers' driving behaviors. A self-developed MATLAB program and statistically significant difference t -test were applied to analyze the impacts of the DSAS messages on drivers' driving performance, in terms of approaching speed profile, acceleration/deceleration rates, braking distance, and possible extra vehicle emissions induced by the introduction of the DSAS message. Drivers' preference on the DSAS was investigated by a designed survey questionnaire among test drivers. Results showed that the DSAS alarm was able to induce drivers to drive significantly slower to approach a STOP sign intersection, perform smaller fluctuation in acceleration/deceleration rates, and be more aware of a coming STOP sign indicated by decelerating earlier. All test drivers preferred to follow the DSAS alarm on roads for a safety concern. Further, the DSAS alarm caused the reduction in emission rates through movement. For a general observation, more road tests with more participants and different test routes were recommended.
Three-Year-Old Children Detect Social Exclusion in Third-Party Interactions

Humans are motivated to connect with others and are sensitive to social exclusion—intentionally leaving out others. This ability to detect social exclusion is suggested to be evolutionarily adaptiv...
Predisposition for Empathy, Intercultural Sensitivity, and Intentions for Using Motivational Interviewing in First Year Pharmacy Students

Objective. To assess first-year pharmacy (P1) students' predispositions (eg, perceptions for empathy, intercultural sensitivity, and motivational interviewing (MI) as a patient-centered communication skillset) and identify potential curricula content/communication skills training needs. Methods. A cross-sectional survey was used to collect students' self-reported perceptions for empathy, intercultural sensitivity, counseling contexts, and projected future MI use. Relationships between variables were explored and logistic regression was used to evaluate intention for using MI in future patient encounters. Results. There were 134 students who participated. Higher predisposition for empathy and for intercultural sensitivity were significantly correlated. Significant predictors for applying MI in future patient encounters were sex, confidence with counseling skills, and current use of MI. Conclusion. Results suggest the need to incorporate innovative training strategies in communication skills curricula. Potential areas include empathy, intercultural sensitivity and significant predictor variables for future MI use. Further investigation in other schools is needed.
Efficient data access in hybrid cloud storage

Hybrid cloud is a widely adopted framework where on-premise storage and/or compute resources are combined with public cloud system. This paper explores the storage aspect of this framework, which requires designing coding schemes that are aware of both local and global components of the available storage space. The coding schemes should provide efficient repair mechanisms for the data stored on the public cloud (global storage space) and utilize the local storage space to facilitate seamless access to the overall information stored on the hybrid cloud storage. This paper presents a mathematical model for hybrid cloud storage which takes all these requirements into account. The paper then extends the information flow graph approach to characterize the fundamental limits on access bandwidth of the system, i.e., the amount of data downloaded from the public cloud during the data reconstruction process. This paper also presents several explicit coding schemes that utilize the available local storage space to attain the fundamental limit on the access bandwidth. The setup where multiple clients with varying local storage spaces are supported by a single global storage space is also addressed.
Lower risk of postoperative arrhythmias in congenital heart surgery following intraoperative administration of magnesium.

Abstract Objectives Postoperative arrhythmias are common in children undergoing congenital heart surgery. We evaluated whether intraoperative administration of magnesium was associated with a reduced occurrence of specific postoperative arrhythmias, as has been described previously, or had a broader effect on multiple arrhythmia types, and 2) whether there existed a dose-effect of intraoperative magnesium. Methods We used a historical prospective observational cohort study. Propensity-score matching using logistic regression was applied to establish similar populations of treatment groups balanced on 5 important covariates. Results Based on propensity-score matched groups, magnesium 50 mg/kg administration was associated with a reduced odds of occurrence of postoperative arrhythmias: any arrhythmia (OR = 0.50, P 001), junctional ectopic tachycardia (OR = 0.56, P=. 004), accelerated junctional rhythm (OR = 0.56, P =.089), atrial tachycardia (OR = 0.48, P =.005), ventricular tachycardia (OR = 0.52, P = . 04), and AV block (OR = 0.47, P =.03). The effect of magnesium on reducing the odds of occurrence of postoperative arrhythmias did not differ between 25 mg/kg vs. 50 mg/kg. Conclusions As many as one third of our congenital heart surgery patients had postoperative arrhythmias. Use of intraoperative magnesium was associated with a reduction in the odds of occurrence of all postoperative arrhythmias. Our results do not provide evidence that a higher dose of magnesium is associated with greater arrhythmia risk reduction. Despite the intraoperative use of magnesium there continued to be a high residual incidence of postoperative arrhythmias, raising the question for studying new or additional agents.
Legal Education as a Pie-Maker: Why Michigan Benefits from Accessible Law Schools

The common view that there are too many lawyers who compete to divide up an ever-shrinking American pie is factually wrong and professionally destructive. Lawyers are pie-makers. They are economic drivers. Legal education produces higher quality human capital that increases gross domestic product. Lawyers increase economic productivity. The responsible professional view is that legal services are a value-add for individuals, families, businesses, and government.
Ghana's Demographic Transition: The Role of Induced Abortion and Reproductive Health Ramifications

Issues pertaining to reproductive health are taken seriously by developing countries, if the Millennium Development Goal of improving maternal health is to be achieved. To meet the targets of reducing by three quarters the maternal mortality ratio and achieve universal access to reproductive health care, research into reproductive needs is of paramount importance. Ghana has been experiencing a reduction in fertility levels over the last two decades. Total fertility rate (TFR), which stood at 6.4 in the late 1980s decreased to 5.5 and 4.6 in 1993 and 1998 respectively and further decreased to 4.4 in 2003. Meanwhile, the contraceptive prevalence rate has remained persistently low at 25 percent. This suggests that other factor(s), besides contraceptive use, may be more important in shaping Ghana’s fertility transition. Although there is no direct information on induced abortion, the application of an indirect technique (neo-residual method) provides insightful clues that induced abortion may chiefly account for the disjoint between Ghana’s declining fertility and the low contraceptive use. Using the 1998 and 2003 Ghana Demographic and Health Surveys, and guided by Bongaarts’ proximate determinants of fertility model, I compute an internal consistency accuracy measure to validate the indirect technique and estimate the fertility inhibiting effects of the proximate determinants. I find that, while postpartum infecundability is the most significant inhibitor of fertility, induced abortion is, increasingly, a major birth inhibitor. In view of these findings, I recommend that, care for complications from abortion should be an integral part of primary health care system.
Guidelines for reports, presentations and publishing

The quality of the presentation of your research results, both in writing and orally, will determine how the audience perceives the work. This chapter presents guidelines for effective technical reports and presentations.
Iontophoretic delivery of a series of tripeptides across the skin in vitro.

The iontophoresis of eight tripeptides, of the general structure alanine–X–alanine, has been measured across hairless mouse skin in vitro. The peptides were blocked (a) at the carboxyl terminus using the mixed anhydride reaction with t-butylamine and (b) at the amino terminus by acetylation with 14C-acetic anhydride. The nature of the central residue (X) was varied by selecting one of five neutral amino acids, two negatively chargeable moieties (aspartic and glutamic acids), and a positively chargeable species (histidine). Constant current iontophoresis at 0.36 mA/cm2, using Ag/AgCl electrodes, was performed for 24 hr in diffusion cells, which allowed both anode and cathode to be situated on the same (epidermal) side of a single piece of skin. Due to a combination of osmotic and electroosmotic forces, the anodal iontophoretic flux of neutral peptides was significantly greater than passive transport. Steady-state fluxes were not achieved, however, suggesting that time-dependent changes in the properties of the skin barrier may be occurring. Limited, further experiments confirmed that, on a 24-hr time scale, these changes were not fully reversible. The cathodal delivery of anionic permeants was well controlled at a steady and highly enhanced rate by the current flow. This behavior closely paralleled earlier work using simple negatively charged amino acids and N-acetylated amino acid derivatives. It appears that the normalized iontophoretic flux of these anionic species is independent of lipophilicity but may be inversely related to molecular weight. The positively charged peptide, Ac–Ala–His–Ala–NH(But), showed greater anodal iontophoretic enhancement when delivered from a donor solution at pH 4.0 than from a solution at pH 7.4. This was consistent with (a) the corresponding behavior of histidine alone and (b) the existence of a pKa for these compounds at ∼6. Steady-state delivery was not achieved, although the levels of enhancement, especially at pH 4, were the largest observed. A preliminary investigation of tripeptide stability to either (i) electrolysis in the donor compartment or (ii) cutaneous metabolism revealed very little degradation under the conditions of the experiment. Overall, this research supports the principle of enhanced peptide delivery across the skin by iontophoresis and indicates a number of areas (e.g., mechanism and extent of current-induced changes in skin barrier function, molecular size dependence, pathways of current flow) on which further work should be focused.
Collaborative capacity and patient-centered care in the Veterans' Health Administration Community Living Centers.

IntroductionPrevious research in acute care settings has shown that collaborative capacity, defined as the way providers collaborate as equal team members, can be improved by the ways in which an o...
Rbm15 Affects Notch Signaling and Myelopoiesis.

Acute Megakaryoblastic Leukemia (AMKL) presents with one of two different genotypic abnormalities; either Down Syndrome (DS) accompanied with GATA-1 mutations, or a non-DS translocation t(1;22)(p13;q13). In AMKL associated with DS, there is trisomy 21 and various partial loss of function mutations in GATA-1. In non-DS AMKL, the translocation t(1;22)(p13;q13) encodes a fusion protein, RBM15-MKL, comprised of the transcriptional co-factors RBM15 (chromosome 1) and MKL (chromosome 22). In order to elucidate the role of the RBM15-MKL fusion protein in AMKL, we must understand the normal functions of RBM15 and MKL. Herein we demonstrate a role for Rbm15 in myeloid differentiation. Previous work in the lab showed that Rbm15 is expressed at highest levels in hematopoietic stem cells, and at more moderate levels during myelopoiesis of murine cell lines and primary murine cells. Therefore, we hypothesized that Rbm15 plays a role in myeloid differentiation. Indeed, we demonstrate that shRNA-mediated knockdown of Rbm15 enhanced the differentiation of 32DWT18 myeloid precursor cells. Recent studies have shown the Rbm15 homolog, Sharp, interacts with RBPJk, a critical transcription factor in the Notch signaling pathway; and since Notch signaling is essential for hematopoiesis, we hypothesized that Rbm15 may also modulate Notch signaling. We demonstrate that Rbm15 alters Notch-induced HES1 promoter activity in a cell-type specific manner. Rbm15 inhibits Notch-induced HES1 activity in non-hematopoietic cell lines, but stimulates this activity in hematopoietic cell lines including 32DWT18 and HEL (human erythroleukemia). In addition, we show that the N-terminus of Rbm15 co-immunoprecipitates with RBPJk and has a dominant negative effect by impairing the activation ability of HES1 promoter activity by full length-Rbm15. Thus, Rbm15 is differentially expressed during hematopoiesis and may act to inhibit myeloid differentiation in hematopoietic cells via a mechanism that is mediated, at least in part, by stimulation of Notch signaling via interaction with RBPJk. Consistent with a potential mechanistic role of Rbm15 and Notch in myelopoiesis, we have shown that shRNA-mediated knockdown of Rbm15 in 32DWT18 cells promotes myeloid differentiation, suggesting that the RBM15 component of the RBM15-MKL fusion protein may act by blocking differentiation. Currently, we are examining the effect of RBM15 overexpression and knockdown in primary mouse bone marrow cells using in vitro and in vivo assays.
Causality in the Fermi problem and the Magnus expansion

Abstract In 1932, Fermi presented a two-atom model for determining whether quantum mechanics is consistent with causality, and concluded that indeed it is. In the late 1960's, Shirokov and others found that Fermi's approximations may not have been sound, and when corrected, Fermi's model shows non-causal behavior. We show that if instead of time-dependent perturbation theory, the Magnus expansion is used to approximate the time-evolution operator, causality does follow.
Detection of LC3-Associated Phagocytosis (LAP)

Phagocytes, notably macrophages, are critical sentinels of their environment, patrolling for and eradicating unwanted components. The ability of cells to process extracellular cargo in an appropriate manner is important for both clearance of the cargo and eventual return to homeostasis. Although the evolutionarily conserved pathway of autophagy involves the degradation and recycling of unnecessary or dysfunctional cellular components during starvation, we now appreciate that the reach of autophagy extends beyond nutrient deprivation, notably including cellular quality control (e.g., mitophagy) and host defense against internalized pathogens (i.e., xenophagy). Despite being seemingly disparate, autophagic functions are unified as conserved mechanisms for containment and immunosuppression, suggesting an original immune function for autophagy. A recently described pathway called LC3-associated phagocytosis (LAP) marries the ancient concepts of phagocytosis and autophagy, revealing new ways in which the autophagy machinery, in a molecularly distinct pathway, contributes to the inflammatory response. In this article, protocols to detect LAP by electron microscopy, immunofluorescence, flow cytometry, and phagosome purification are described, allowing the user to detect multiple characteristics of LAP in both qualitative and quantitative manners. Published 2020. U.S. Government. Basic Protocol 1: Detection of LAP by electron microscopy Basic Protocol 2: Detection of LAP by confocal microscopy of LC3-GFP-expressing cells Alternate Protocol 1: Detection of LAP by confocal microscopy using immunofluorescence Basic Protocol 3: Detection of LAP using flow cytometry of LC3-GFP-expressing cells Alternate Protocol 2: Detection of LAP using antibody staining and flow cytometry Basic Protocol 4: Detection of LAP by western blot of purified LAPosomes.
Examination of a novel measure of trauma-related drinking to cope.

Objectives The present study sought to fill a gap in the current literature by developing a concise self-report questionnaire assessing drinking motives specific to coping with symptoms of posttraumatic stress disorder (PTSD). This new four-item questionnaire is called the Trauma Related Drinking questionnaire (TRD). Method Using structural equation modeling, the latent structure of the TRD items and how they relate to other variables of interest were explored among a sample of 1,896 college undergraduates from a large public university. Results Broadly, we found evidence to suggest that TRD is a more specific measure of drinking to cope motives compared to the commonly used Drinking Motives Questionnaire coping subscale. Additionally, findings demonstrate support for the external validation of TRD, both with regard to PTSD and alcohol consumption and related problems. Conclusions Results support the use of TRD in future self-medication research and as a clinically useful screening tool.
Synergistic health effects of air pollution, temperature, and pollen exposure: a systematic review of epidemiological evidence

Exposure to heat, air pollution, and pollen are associated with health outcomes, including cardiovascular and respiratory disease. Studies assessing the health impacts of climate change have considered increased exposure to these risk factors separately, though they may be increasing simultaneously for some populations and may act synergistically on health. Our objective is to systematically review epidemiological evidence for interactive effects of multiple exposures to heat, air pollution, and pollen on human health. We systematically searched electronic literature databases (last search, April 29, 2019) for studies reporting quantitative measurements of associations between at least two of the exposures and mortality from any cause and cardiovascular and respiratory morbidity and mortality specifically. Following the Navigation Guide systematic review methodology, we evaluated the risk of bias of individual studies and the overall quality and strength of evidence. We found 56 studies that met the inclusion criteria. Of these, six measured air pollution, heat, and pollen; 39 measured air pollution and heat; 10 measured air pollution and pollen; and one measured heat and pollen. Nearly all studies were at risk of bias from exposure assessment error. However, consistent exposure-response across studies led us to conclude that there is overall moderate quality and sufficient evidence for synergistic effects of heat and air pollution. We concluded that there is overall low quality and limited evidence for synergistic effects from simultaneous exposure to (1) air pollution, pollen, and heat; and (2) air pollution and pollen. With only one study, we were unable to assess the evidence for synergistic effects of heat and pollen. If synergistic effects between heat and air pollution are confirmed with additional research, the health impacts from climate change-driven increases in air pollution and heat exposure may be larger than previously estimated in studies that consider these risk factors individually.
On information projections between multivariate elliptical and location-scale families.

We study information projections with respect to statistical $f$-divergences between any two location-scale families. We consider a multivariate generalization of the location-scale families which includes the elliptical and the spherical subfamilies. By using the action of the multivariate location-scale group, we show how to reduce the calculation of $f$-divergences between any two location-scale densities to canonical settings involving standard densities, and derive thereof fast Monte Carlo estimators of $f$-divergences with good properties. Finally, we prove that the minimum $f$-divergence between a prescribed density of a location-scale family and another location-scale family is independent of the prescribed location-scale parameter. We interpret geometrically this property.
Infectious Complications Predict Premature CD8+ T-cell Senescence in CD40 Ligand-Deficient Patients.

CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. CD8+ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed CD8+ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. Peripheral CD8+ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory CD8+ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of CD8+ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. Our findings support that recurrent infections and non-adherence to prophylaxis promote early CD8+ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients.
Mathematical modeling shows that ball-rolling dung beetles can use dances to avoid competition

Ball-rolling dung beetles shape a portion of dung into a ball and roll it away from the dung pile for later burial and consumption. These beetles perform dances (rotations and pauses) atop their dung balls in order to choose an initial rolling direction and to correct their rolling direction (reorient). Previous mathematical modeling showed that dung beetles can use reorientation to move away from the dung pile more efficiently. In this work, we study whether reorientation can help beetles avoid competition (i.e., avoid having their dung balls captured), and if so, under what circumstances? This is investigated by implementing a model with two different type of beetles, a roller with a dung ball and a searcher which seeks to capture that dung ball. We show that reorientation can help rollers avoid searchers in a wide range of conditions, but that there are some circumstances in which rolling without reorienting can be a beetle’s optimal strategy. We also show that rollers can minimize the probability that their dung ball is captured without making precise measurements of the time interval between dances or the angular deviation for dances.
Aging out of the federal dependent coverage mandate and purchases of prescription drugs with high rates of misuse.

Abstract Prescription central nervous system depressants, opioid pain relievers, and stimulants provide therapeutic value, but misuse for their recreational value is a growing problem in the United States. Because health insurance lowers the cost of purchasing prescription drugs, losing coverage may cause individuals to forgo treatment and decrease prescription drug consumption which could reduce health and increase the likelihood of overdose and death if individuals substitute to using illicit drugs. I estimate the reduced form effect of aging out of the federal dependent coverage mandate at age 26 on legal purchases of prescription central nervous system depressants, opioids, and stimulants. Individuals are 0.5–0.9% points less likely to purchase a prescription central nervous system depressant and 0.8–1.5% points less likely to purchase a prescription opioid after turning 26. These effects are strongest for women, while estimated effects for men are generally negative but imprecise.
EXPERIMENTAL MEASUREMENTS OF THE INDEPENDENT EFFECTS OF DILUTION RATIO AND FILTER TEMPERATURE ON DIESEL EXHAUST PARTICULATE SAMPLES

A dilution mini-tunnel is described that collects diesel exhaust particulate samples with independent control of dilution ratio and sample filter temperature. The small dilution system requires no pumps or blowers and offers much flexibility in controlling the dilution process. Experiments were conducted with the dilution system to establish individual effects of filter temperature and dilution ratio on particulate samples collected by filtration from the exhaust of an automotive diesel engine. Exhaust particulate aerosol was generated with a single-cylinder test engine operating at constant load and speed. Increasing filter temperature from 35-100 degrees C while maintaining a constant 10.8:1 dilution ratio decreased particulate mass by about 13%. Increasing the dilution ratio from 5:1 to 100:1 at a constant filter temperature of 52 degrees C decreased particulate mass by about 26%. These changes were attributed to variations in the soluble portion of the particulate sample. Supplemental information is appended on dilution system development, residence time and filter material effects on particulate mass, and dilution ratio calculation.
Fast Kinetics of Calcium Signaling and Sensor Design

Fast calcium signaling is regulated by numerous calcium channels exhibiting high spatiotemporal profiles which are currently measured by fluorescent calcium sensors. There is still a strong need to improve the kinetics of genetically encoded calcium indicators (sensors) to capture calcium dynamics in the millisecond time frame. In this review, we summarize several major fast calcium signaling pathways and discuss the recent developments and application of genetically encoded calcium indicators to detect these pathways. A new class of genetically encoded calcium indicators designed with site-directed mutagenesis on the surface of beta-barrel fluorescent proteins to form a pentagonal bipyramidal-like calcium binding domain dramatically accelerates calcium binding kinetics. Furthermore, novel genetically encoded calcium indicators with significantly increased fluorescent lifetime change are advantageous in deep-field imaging with high light-scattering and notable morphology change.
Optimal Irrigation Pivot Location on Irregularly Shaped Fields

th e groing season. Annual its distribution poses special problems on small, irregularly is a potential conadequate; however, its distribution shaped fields In the southeastern United is a potential constraint to agricultural proshaped fields. In the southeastern United Owsley) Thus, annual States, field size and shape are often varied dution (tz and Osle. Ts nn and irregular. A mixed integer programming ranfall data can provide misleading impre sion of the usefulness of irrigation technolmodel was constructed to assist in irrigation irrigation technolinvestment decisions. The model is illus- ogy. Several techniques have been developed trated using irrigated peanut production in Several techniques have been developed southeast Alabama. Results indicate the im- to optimize irrigation resource allocation. portance of economic engineering consid- Trava et al. used a linear programming model erations. to determine the date and quantity of water to apply to agricultural crops. Integer proKey words: mixed integer programming, gramming was incorporated to specify the supplemental irrigation, eco- decision to irrigate. Udeh and Busch incornomic engineering. porated Bayesian decision theory into an opSelection of the optimal position, size, timal irrigation management strategy model to address stochastic, probabilistic, and risk and number of pivots in a center pivot irri- to address stochastic, probabilistic, and risk gation system poses special problems on elements. In addition, optimal irrigation water small, irregularly shaped fields. In the south- use from probability distributions of evapoeastern United States, field size and shape are transpiration and benefit-cost analyses of iroften varied and irregular. Irrigation tech- rigation systems has been estimated (Khannology is rapidly being adopted; however, 1 a d l a mh t de nology is rapidly being adopted; however, jani and Busch, 1982). Khanjani and Busch most research on center pivot irrigation sys- (1983) also developed a method to detertems has focused on large regularly shaped mine optimal size and location of farm irrifields. Farmers in the Southeast require pro- gation reservoirs. duction information concerning the efficient A technique has been developed that deuse of irrigation technology adapted to re- scribes a field as a series of grid points and gional growing conditions. This paper ap- attempts to analyze field coverage by center plies a new methodology for selection of the pivot irrigation systems (Rochester). An inoptimal number, size, and position of irri- teger programming analysis was utilized to gation pivots that may be used with any field determine the optimal locations and number size or shape. of center pivots that would maximize covMost irrigation research has focused on arid erage of the field (Anderson et al.). Solutions regions because of the obvious importance were obtained which examined the effect of of water in these areas (Ruttan; Burt and two different irrigation strategies: one per