cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5512: Dual inhibition of AXL and FN14 reverses cisplatin resistance in non-small cell lung carcinoma by inducing higher caspase 3 cleavage

Background and Objectives: NSCLC patients undergoing Cisplatin therapy often develop resistance within 9-12 months that decreases treatment efficacy and is the major reason for the low median survival of 10-14 months among stage IV patients. Therefore, resistance is the main therapeutic limitation in the later part of the progressive disease. It has been suggested that suppressed Caspase-3 is one of the major reasons for failure to induce apoptosis by the cell during cisplatin resistance. We hypothesized this resistance to be related to EMT and other survival pathways. Recently, AXL and TWEAK/FN14 pathways have been shown to be upregulated in cisplatin resistant cells causing activation of EMT and survival pathways. Therefore, we examined whether dual inhibition of AXL and TWEAK/FN14 successfully reverses the cisplatin resistance in NSCLC. Materials and Methods: Drug resistant EGFR mutant H1975 and KRAS mutant A549 cells were tested for cisplatin desensitization following knock down of AXL and FN14 inhibition. We studied resensitization by determining the IC50 values in the drug resistant cell lines by treatment with both AXL and FN14 siRNA. We investigated detailed cellular mechanisms imparting resistance by detecting relative levels of Caspase 3, cleaved Caspase 3, PARP, cleaved PARP, p-SRC, p-EGFR, AXL and FN14 by western blotting. Cytochrome-C induced apoptosis was detected by monitoring cytochrome-c released from mitochondria using fluorescence microscopy. Results: Suppression of AXL and FN14 by siRNA treatment resensitized NSCLC to cisplatin and induced apoptosis. IC50 values were decreased significantly following dual inhibition (by more than 200%). A marked increase in cleaved caspase 3 levels was also observed in both mutant cell lines. A subsequent increase in PARP and cleaved PARP levels verified the fact that caspase 3 is indeed responsible for the apoptosis in these cells. Upregulation of p-SRC and eventually p-EGFR failed to suppress the apoptosis through PI3K/AKT pathway. Cytochrome c release from mitochondria further confirmed cellular apoptosis. Conclusion: Our results show that dual inhibition of AXL and TWEAK/FN14 can reverse cisplatin resistance by inducing higher caspase 3 cleavage that can enhance survival of NSCLC patients undergoing chemotherapy. Citation Format: Soumavo Mukherjee, Dhananjay Suresh, Ajit P. Zambre, Anandhi Upendran, Raghuraman Kannan. Dual inhibition of AXL and FN14 reverses cisplatin resistance in non-small cell lung carcinoma by inducing higher caspase 3 cleavage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5512.
Examining Recent Hookah Use, Other Substance Use, and Substance Use Prevention Education Among College Students

ABSTRACTBackground: Hookah tobacco use is an emerging public health problem. Purpose: The purpose of the present study is to examine recent hookah tobacco use among college students and potential correlates including other drugs and drug education. Methods: The paper version of the National College Health Assessment II was completed by 765 students enrolled at one urban university. Results: Findings indicated that 14.2% of students used hookah in the past 30 days. Significant differences were found based on recent alcohol, recent cigarette use, recent cigar use, recent smokeless tobacco use, and recent marijuana use. Students who received tobacco education were at increased odds for hookah use (χ2 = 5.592, df = 1, P = .018). The final regression model predicted recent hookah use (omnibus χ2 = 129.779, df = 6, P < .001) and accounted for 15.6% to 28.0% of the variance in recent hookah use. Discussion: Students using hookah were found to use other type of substances, which may warrant attention on college c...
Smartphone technology can measure postural stability and discriminate fall risk in older adults.

Abstract Background Falls are the leading cause of injury related death in older adults. Impaired postural stability is a predictor of falls but is seldom objectively assessed in clinical or home settings. Embedded accelerometers within smartphones offer potential to objectively measure postural stability. The purpose of this study was to determine if a smartphone embedded accelerometer can measure static postural stability and distinguish older adults at high levels of fall risk. Methods Thirty older adults (age: 65.9 ± 8.8) underwent seven balance tests while standing on a force plate and holding a smartphone against their chest in a standardized order. Participants also completed the Physiological Profile Assessment to assess their fall risk. Center of pressure (COP) parameters from the force plate including velocity in the anterioposterior (AP) and mediolateral (ML) directions and 95% confidence ellipse were derived. Maximum acceleration and root mean square (RMS) in ML, AP and vertical axes were derived from the smartphone. Spearman rank-order correlations between force plate and smartphone measures were conducted, and receiver operating characteristic (ROC) and the area under the curves (AUC) were constructed to distinguish between low and high fall risk. Results There were moderate to strong significant correlations between measures derived from the force plate and measures derived from the smartphone during challenging balance conditions (ρ = 0.42–0.81; p Significance This study provides evidence that a smartphone is a valid measure of postural stability and capable of distinguishing fall risk stratification in older adults. There is potential for smartphones to offer objective, fall risk assessments for older adults.
The Role of Regional Contrast Changes and Asymmetry in Facial Attractiveness Related to Cosmetic Use

This study collected behavioral data for testing how regional contrast changes due to the addition of cosmetics would affect attractiveness ratings. In addition, we used an established model of asymmetry to look for a correlation between changes in attractiveness related to the application of cosmetics to specific regions of the face and changes in symmetry. Using this asymmetry model we compared female faces with and without makeup. Specifically, we used a highly controlled set of grayscale faces in which makeup application was standardized to explore these issues from a perceptual perspective. The human data showed that adding upper eye makeup significantly increased attractiveness ratings. In contrast, increases in contrast to the lower eyes and lips did not lead to increases in attractiveness ratings; application of cosmetics to the lower eyes led to a significant decrease in attractiveness. We found that for the makeup condition that led to increased attractiveness, asymmetry did not change significantly when makeup was applied to the female faces. This suggests a role for mechanisms other than symmetry related to increases in attractiveness related to makeup use in females.
Interpretation of androgen and anti-Mullerian hormone profiles in a Hispanic cohort of 5- to 8-year-old girls with premature adrenarche.

Purpose Premature adrenarche (PA) often leads to polycystic ovary syndrome (PCOS). Higher anti-mullerian hormone (AMH) levels are reported in PCOS. We studied the androgen profile and AMH profiles in Hispanic girls with PA (aged 5-8 years) and age and body mass index (BMI) matched controls. Methods Retrospective review of electronic medical records of girls who met the inclusion criteria for premature adrenarche were done. Results PA girls (n=76) were matched to control girls (n=12) for age (mean±standard deviation) (6.7±1 years vs. 6.2±1.3 years) and BMI (20±10 kg/m2 vs. 17.8±2.7 kg/m2). Dehydroepiandrostenedione sulfate (63.3±51.3 μg/dL vs. 29.8±17.3 μg/dL, Pl0.001) and testosterone levels (11.4±4.8 ng/dL vs. 8.2±2.9 ng/dL, P=0.001) were significantly higher in the PA group than controls. AMH values (l14 years: reference range, 0.49-3.15 ng/mL) were 3.2±2.2 ng/mL vs. 4.6± 3.2 ng/mL respectively in the PA and control groups and were not different (P=0.4). AMH did not show a correlation with bone age (P=0.1), and testosterone (P=0.9) in the PA group. 17-hydroxyprogesterone levels (17-OHP ng/dL) were 39.5±30.5 ng/dL vs. 36.8±19.8 ng/dL in PA versus control girls. The concentration of 17-OHP was not statistically different between the control and PA groups. Conclusion Higher AMH was not observed in PA girls and no correlation with BA and androgen levels was observed.
Impact of a Women-focused Professional Organization on Academic Retention and Advancement: Perceptions From a Qualitative Study.

Objectives Organizations to promote career networking and mentorship among women are recommended as a best practice to support the recruitment and retention of women physicians; however, the impact of such organizations is unknown. Our primary objective is to describe the impact of a national woman-focused organization for academic emergency physicians on retention and advancement. Methods We conducted semistructured interviews of past and present organization leaders, as well as members at varying stages in their careers. Physicians with experience in qualitative methods conducted interviews and coded all transcripts using inductive content analysis techniques. Themes were reviewed and discussed to ensure consensus. Results We performed 17 interviews lasting 20 to 30 minutes each, resulting in 476 total minutes of transcript. Participants represented varying stages of career experience, ranging from 2 to 35 years since residency completion (median = 9.5 years). Median years of participation in the woman-focused organization was 10 years. Over half (53%) of participants were past presidents of the organization. The dominant themes encompassed facilitating academic advancement through scholarly productivity, leadership experiences, awards, and promotions; mentorship and sponsorship; peer support and collaborations; reduced professional isolation; and initiatives to address systemic gender inequities and challenges, including strategies to navigate bias, promote pay equity, and advocate for family-friendly workplace policies. Discussion Active participation in a woman-focused professional organization enhances members' career retention and advancement by creating opportunities and relationships that facilitate leadership, enabling scholarly work to advance equity and inclusion, and cultivating a sense of belonging. While challenges and barriers persist, the myriad benefits of a women-focused professional organization reported by members and leaders represent important steps toward greater equity for women and other underrepresented groups in academic medicine.
Validation of a symptom-based questionnaire for pediatric CNS demyelinating diseases.

Purpose Optic neuritis is a manifestation of numerous neuroinflammatory disorders. Recognition of current and prior symptoms may facilitate identification of an underlying multifocal neurologic disease. The purpose of this study was to determine whether a symptom-based questionnaire could inform clinical decision making by identifying children with visual complaints who may have a systemic demyelinating disorder. Methods Children with visual changes from non-demyelinating disease were compared with patients with confirmed pediatric-onset multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Participants completed a 21-item questionnaire to capture their recent ( 30 days) symptoms of neurologic dysfunction. The questionnaire scores were compared using t tests, and the 95% confidence interval for each group was used to determine a threshold score suggesting demyelinating disease. Results We enrolled 51 participants (30 females [59%]) with a mean age of 14.6 years (range, 4-21): 25 in the non-demyelinating disease group and 26 with MS/NMOSD. The mean questionnaire score for the non-demyelinating group was 5.0 points (95% CI, 3.3-6.9); for the MS/NMOSD group, 9.4 points (95% CI, 7.4-11.4) for the MS/NMOSD group (P Conclusions A symptom-based questionnaire is sensitive and specific for identifying children with CNS demyelinating disease and may be useful as a screening tool for children with vision complaints and possible demyelination.
Learning effective changes for software projects

The primary motivation of much of software analytics is decision making. How to make these decisions? Should one make decisions based on lessons that arise from within a particular project? Or should one generate these decisions from across multiple projects? This work is an attempt to answer these questions. Our work was motivated by a realization that much of the current generation software analytics tools focus primarily on prediction. Indeed prediction is a useful task, but it is usually followed by ``planning'' about what actions need to be taken. This research seeks to address the planning task by seeking methods that support actionable analytics by offering clear guidance on what to do. Specifically, we propose XTREE and BELLTREE algorithms for generating a set of actionable plans within and across projects. Each of these plans, if followed will improve the quality of the software project.
Understanding the Major Factors Affecting Response Shift Effects on Health-Related Quality of Life: What the Then-Test Measures in a Longitudinal Prostate Cancer Registry

Abstract Background Localized prostate cancer (PCa) treatments provide high survival rates, with patients often surviving a decade or longer after treatment. Therefore, treatment options are progressively based on quality of life. The objective of this research was to investigate magnitude of response shift (RS) in health-related quality of life (HRQOL) responses in men with clinically localized PCa using a generic questionnaire and a disease-specific questionnaire in an observational longitudinal patient registry study. Patients and Methods A cohort study was conducted using the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database. Patients were annually surveyed using the Medical Outcomes Study Questionnaire Short Form 36 (SF-36) and the UCLA Prostate Cancer Index (PCI) HRQOL measures. A total of 3161 active patients were eligible for a one-off supplemental study asking retrospective HRQOL scores (then-test). We calculated RS, observed change, and RS adjusted change. Statistical difference was determined by t test. Results Patients consistently reported higher recalled pretreatment HRQOL compared to baseline scores for SF-36 and PCI, confirming the existence of a RS (P Conclusion RS occurrence was measured in both the disease-specific questionnaire and the generic HRQOL questionnaire, demonstrating continued low health and symptom scores after RS adjustment. Therefore, health professionals should adjust for this phenomenon when assessing patient’s HRQOL treatment responses, and clinicians should address their continued sexual and urinary functional loss.
Random Network Coding Enabled Routing in Swarm Unmanned Aerial Vehicle Networks

Routing protocol design is one of the major challenges for swarm UAV networks. Due to the characteristics of a dynamic network topology, the low-complexity and the large volume of UAV devices, existing routing protocols based on network topology information, and routing table updates are not applicable in swarm UAV networks. In this paper, a Random Network Coding (RNC) enabled routing protocol is proposed to support an efficient routing process, which does not require network topology information or pre-determined routing tables. With the proposed routing protocol, the routing process could be significantly expedited, since each forwarding UAV may have already overheard some encoded packets in previous hops. As a result, some hops may be required to deliver a few encoded packets, and less hops may need to be completed in the whole routing process. The corresponding simulation study is conducted, demonstrating that our proposed routing protocol is able to facilitate a more efficient routing process.
Over What Length Scale Does an Inorganic Substrate Perturb the Structure of a Glassy Organic Semiconductor

US Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering, Award DE-SC0002161.
Generation of a chromosome-scale genome assembly of the insect-repellent terpenoid-producing Lamiaceae species, Callicarpa americana.

Background Plants exhibit wide chemical diversity due to the production of specialized metabolites that function as pollinator attractants, defensive compounds, and signaling molecules. Lamiaceae (mints) are known for their chemodiversity and have been cultivated for use as culinary herbs, as well as sources of insect repellents, health-promoting compounds, and fragrance. Findings We report the chromosome-scale genome assembly of Callicarpa americana L. (American beautyberry), a species within the early-diverging Callicarpoideae clade of Lamiaceae, known for its metallic purple fruits and use as an insect repellent due to its production of terpenoids. Using long-read sequencing and Hi-C scaffolding, we generated a 506.1-Mb assembly spanning 17 pseudomolecules with N50 contig and N50 scaffold sizes of 7.5 and 29.0 Mb, respectively. In all, 32,164 genes were annotated, including 53 candidate terpene synthases and 47 putative clusters of specialized metabolite biosynthetic pathways. Our analyses revealed 3 putative whole-genome duplication events, which, together with local tandem duplications, contributed to gene family expansion of terpene synthases. Kolavenyl diphosphate is a gateway to many of the bioactive terpenoids in C. americana; experimental validation confirmed that CamTPS2 encodes kolavenyl diphosphate synthase. Syntenic analyses with Tectona grandis L. f. (teak), a member of the Tectonoideae clade of Lamiaceae known for exceptionally strong wood resistant to insects, revealed 963 collinear blocks and 21,297 C. americana syntelogs. Conclusions Access to the C. americana genome provides a road map for rapid discovery of genes encoding plant-derived agrichemicals and a key resource for understanding the evolution of chemical diversity in Lamiaceae.
High failure rates following ligation of the intersphincteric fistula tract for transsphincteric anal fistulas: are preoperative MRI measurements of the fistula tract predictive of outcome?

Aim Treatment of transsphincteric fistulas (TSFs) with fistulotomy after an indwelling seton is tempered by risks of incontinence and litigation. Thus, ligation of the TSF tract has been popularized as an alternative option. We previously reported on 107 patients who underwent ligation of the intersphincteric fistula tract (LIFT), with a 46% failure rate. Posterior fistula was the only predictor of recurrence. The aim of the present work was to investigate whether the length, width or depth of the fistula measured on preoperative MRI was correlated with recurrence. Method Following institutional review board approval, a retrospective analysis of our prospective Complex Anal Fistula Database from 1 January 2011 to 31 August 2019 was performed. Patients with TSF who underwent preoperative MRI and LIFT were included. Fistula location was classified as anterior, posterior or lateral. MRI measurements of fistula length, width and depth (in the intersphincteric groove) were performed. The type and rate of postoperative recurrence were analysed. Results 173 patients underwent MRI for an anal fistula; of these 40 underwent LIFT and 22/40 (55%) had preoperative MRI. There was no difference in the length, width or depth of anterior (n = 9), posterior (n = 7) or lateral (n = 6) fistula tracts. The overall recurrence rate was 9/22 (41%). Posterior TSFs had the highest recurrence rate (5/7, 71%). Conclusion The mean length, width, and depth of the fistula tract, measured at the preoperative site of LIFT in the intersphincteric groove, did not correlate with recurrence regardless of fistula location.
Do behavioral pharmacology findings predict clinical trial outcomes? A proof-of-concept in medication development for alcohol use disorder.

Behavioral pharmacology paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). However, the degree to which early efficacy in the human laboratory predicts clinical efficacy remains unclear. To address this gap in the literature we employed a novel meta-analytic approach. We searched the literature for medications tested for AUD using both behavioral pharmacology (i.e., alcohol administration) and randomized clinical trials (RCTs). For behavioral pharmacology, we computed medication effects on alcohol-induced stimulation, sedation, and craving during the alcohol administration (k = 51 studies, 24 medications). For RCTs, we computed medication effects on any drinking and heavy drinking (k = 118 studies, 17 medications). We used medication as the unit of analysis and applied the Williamson-York bivariate weighted least squares estimation to preserve the errors in both the independent and dependent variables. Results, with correction for publication bias, revealed a significant and positive relationship between medication effects on alcohol-induced stimulation (β = 1.18 p < 0.05), sedation (β = 2.38, p < 0.05), and craving (β = 3.28, p < 0.001) in the laboratory, and drinking outcomes in RCTs, such that medications that reduced stimulation, sedation, and craving during the alcohol administration were associated with better clinical outcomes. A leave-one-out Monte Carlo analysis examined the predictive utility of these laboratory endpoints for each medication. The observed clinical effect size was within one standard deviation of the mean predicted effect size for all but three pharmacotherapies. This proof-of-concept study demonstrates that behavioral pharmacology endpoints of alcohol-induced stimulation, sedation, and craving track medication effects from the human laboratory to clinical trial outcomes. These results apply to alcohol administration phenotypes and may be especially useful to medications for which the mechanisms of action involve alterations in subjective responses to alcohol (e.g., antagonist medication). These methods and results can be applied to a host of clinical questions and can streamline the process of screening novel compounds for AUD. For instance, this approach can be used to quantify the predictive utility of cue-reactivity screening models and even preclinical models of medication development.
The STEM Pipeline: Do Media and Objectified Body Consciousness Create an Early Exit for Middle School Girls?:

Girls and women are underrepresented in science, technology, engineering, and mathematics (STEM) fields. Research has investigated various explanatory factors (e.g., lack of role models, sexism) in...
Paternal Stress and Child Outcomes in Youth with Sickle Cell Disease.

OBJECTIVE The objective of this study was to investigate the relationship between parental stress and health-related quality of life (HRQOL) among children with sickle cell disease (SCD). METHODS A cross-sectional correlational survey research design was used for this quantitative study. One hundred-fifty patients between the ages of 8-17 years old and their caregivers were enrolled from an outpatient comprehensive sickle cell program within a hospital setting. Patients completed the Pediatric Quality of Life Scale 3.0 SCD Module, whereas parents completed the Parental Stress Scale and demographic information questionnaire. Multiple regression analysis was used to determine if parental stress scores predicted the HRQOL of children diagnosed with SCD after controlling for demographic variables. RESULTS The sample included 150 patients (median age: 12 years old; female: 52%) who were diagnosed with SCD along with 150 of their caregivers. Higher levels of parental stress predicted lower HRQOL scores (p < .001). CONCLUSION As parents reported elevated levels of stress related to caring for their child with SCD, patients reported worsening HRQOL. More evidence is needed in order to determine, which constructs of parental stress had a significant impact on HRQOL. It may be helpful for healthcare workers to be aware of familial influences of reduced HRQOL among children diagnosed with SCD. Parents reporting increased stress related to raising their child with SCD may benefit from additional support and resources.
Slippage in the Conservation Reserve Program or Spurious Correlation? A Comment

The Conservation Reserve Program (CRP) pays farmers about $2 billion per year to retire cropland under ten- to fifteen-year contracts. Recent research by Wu found that slippage - an unintended stimulus of new plantings - offsets some of CRP's environmental benefits. Wu does not account for the endogeneity of CRP enrollments. Furthermore, the data used by Wu cannot be used to estimate slippage arising from a price feedback effect. We replicate Wu's findings, demonstrate the possible presence of spurious correlation, and construct new estimates with corrections for endogeneity and other econometric problems. We find no convincing evidence of slippage.
Forward: Achieving Access to Justice Through ADR: Fact or Fiction?

This Foreword offers an overview of Achieving Access to Justice Through ADR: Fact or Fiction?, a symposium hosted by the Fordham Law Review and cosponsored by the National Center for Access to Justice and Fordham Law School’s Conflict Resolution and ADR Program. Access to justice is a foundational value in our system of law and alternative dispute resolution (ADR) is enthusiastically promoted as a vehicle for providing that access. This is as true in developing countries as it is in the United States. For parties, ADR promises autonomy, self-determination, and empowerment. For courts, there is the attraction of procedural and administrative reforms and greater efficiencies. An important question raised in this Symposium is whether ADR has delivered on its promises. Does it in fact provide access to justice or does it facilitate access to injustice for certain segments of society? Reflecting on these questions, this Symposium will offer a critical analysis of ADR’s access to justice claims and consider the extent to which they should be more modest.
International Law and the Latin American Political Refugee Crisis

This mass exodus of refugees apparently has altered the perceptions of some Latin American states regarding asylum. Latin American states have joined the Organization of American States (OAS) and the United Nations High Commissioner for Refugees (UNHCR) in suggesting changes to the traditional inter-American practice of asylum. These suggestions concern the modification of both the existing inter-American asylum conventions and the inter-American human rights system. This article discusses the possibility of transforming inter-American asylum practices on two dimensions the contractual and the evolutionary. Specific actions directed toward either dimension could transform current inter-American asylum practices so as to transfer concern from individual asylees to concern for the mass exodus of refugees.
Environmental trade-offs across cascading lithium-ion battery life cycles

The purpose of this study was to analyze the environmental trade-offs of cascading reuse of electric vehicle (EV) lithium-ion batteries (LIBs) in stationary energy storage at automotive end-of-life. Two systems were jointly analyzed to address the consideration of stakeholder groups corresponding to both first (EV) and second life (stationary energy storage) battery applications. The environmental feasibility criterion was defined by an equivalent-functionality lead-acid (PbA) battery. A critical methodological challenge addressed was the allocation of environmental impacts associated with producing LIBs across the EV and stationary use systems. The model also tested sensitivity to parameters such as the fraction of battery cells viable for reuse, service life of refurbished cells, and PbA battery efficiency. From the perspective of EV applications, cascading reuse of an LIB in stationary energy storage can reduce net cumulative energy demand and global warming potential by 15 % under conservative estimates and by as much as 70 % in ideal refurbishment and reuse conditions. When post-EV LIB cells were compared directly to a new PbA system for stationary energy storage, the reused cells generally had lower environmental impacts, except in scenarios where very few of the initial battery cells and modules could be reused and where reliability was low (e.g., life span of 1 year or less) in the secondary application. These findings demonstrate that EV LIB reuse in stationary application has the potential for dual benefit—both from the perspective of offsetting initial manufacturing impacts by extending battery life span as well as avoiding production and use of a less-efficient PbA system. It is concluded that reuse decisions and diversion of EV LIBs toward suitable stationary applications can be based on life cycle centric studies. However, technical feasibility of these systems must still be evaluated, particularly with respect to the ability to rapidly analyze the reliability of EV LIB cells, modules, or packs for refurbishment and reuse in secondary applications.
Ultra-wideband systems for data communications

Ultra-wideband (UWB) is a radio transmission scheme that uses extremely low power pulses of radio energy spread across a wide spectrum of frequencies. UWB has several advantages over conventional continuous wave radio communications including potential support for high data rates, robustness to multipath interference and fading. We present an overview of UWB technology and its use in data communications and networking. We look at design considerations for UWB based networks at various layers of the protocol stack.
Biological Effects of Novel Bovine Milk Fractions

Novel dairy fractions have been isolated and are now commercially available. Several of them have been shown to have biological activities in various test systems. α-Lactalbumin was first isolated to provide a good source of tryptophan, often the first limiting amino acid in infant formulas, but has then been shown to be digested into smaller peptides with antimicrobial and prebiotic activities, immunostimulatory effect and acting as enhancers of mineral absorption. Lactoferrin bioactivities include antibacterial and antiviral effects, regulation of immune function, stimulation of intestinal proliferation and differentiation and facilitating iron absorption, but these activities may have been limited due to earlier contamination with LPS. Lactoferrin free of lipopolysaccharide may prove to be more effective with regard to exerting these activities. Osteopontin is a heavily phosphorylated and glycosylated protein that modulates immune function and stimulates Th1/Th2 switching, and, possibly, also affects bone mineralization and growth. Biological activities of lactoferrin may be facilitated by osteopontin. Milk fat globule membranes are a fraction that has previously been excluded from infant formulas, but components of this fraction have been shown to exhibit antimicrobial activities and to prevent infection. Further clinical studies are needed on infants fed formulas with these components incorporated.
Design of a long endurance Titan VTOL vehicle

Saturn's moon Titan promises insight into numerous key scientific questions, many of which can be investigated only by in situ exploration of its surface and atmosphere. This paper presents research on a vertical takeoff and landing (VTOL) vehicle designed to conduct a scientific investigation of Titan's atmosphere, clouds, haze, surface, and any possible oceans. Multiple options for vertical takeoff and horizontal mobility were considered. A helicopter was baselined because of its many advantages over other types of vehicles, particularly in that it has access to hazardous terrain and the ability to perform low speed aerial surveys. Using a nuclear power source and the atmosphere of Titan, a turbo expander cycle produces the 1.9 kW required by the vehicle for flight and mission operations, allowing it to sustain a long range, long duration mission that could travel over a thousand kilometers. The turbo expander power source can increase the lifespan and quality of science for planetary aerial flight to an extent that the limiting factor for the mission life is not available power but the life of the mechanical parts. This design is the first to investigate the implications of this potentially revolutionary technology on a Titan aerial vehicle.
Peroxisome proliferator‐activated receptor agonist treatment of alcohol‐induced hepatic insulin resistance

Chronic ethanol exposure impairs insulin signaling in the liver. Peroxisome-proliferator activated receptor (PPAR) agonists function as insulin sensitizers and are used to treat type 2 diabetes mellitus. We examined the therapeutic effectiveness of PPAR agonists in reducing alcoholic hepatitis and hepatic insulin resistance in a model of chronic ethanol feeding. Adult male Long Evans rats were pair fed with isocaloric liquid diets containing 0% (control) or 37% ethanol (caloric content; 9.2% v/v) for 8 weeks. After 3 weeks on the diets, the rats were treated with vehicle, or a PPAR-α, PPAR-δ, or PPAR-γ agonist twice weekly by i.p. injection. Livers were harvested for histopathological, gene expression (RT-PCR), protein (Western and ELISA), and receptor binding studies. Ethanol-fed rats developed steatohepatitis with disordered hepatic chord architecture, increased hepatocellular apoptosis, reduced binding to the insulin, IGF-1, and IGF-2 receptors, and decreased expression of glyceraldehyde-3-phosphate dehydrogenase and aspartyl-(asparaginyl)-β-hydroxylase (mediates remodeling), which are regulated by insulin/IGF signaling. PPAR-α, PPAR-δ, or PPAR-γ agonist treatments reduced the severity of ethanol-mediated liver injury, including hepatic architectural disarray and steatosis. In addition, PPAR-δ and PPAR-γ agonists reduced insulin/IGF resistance and increased insulin/IGF-responsive gene expression. In conclusion, PPAR agonists may help reduce the severity of chronic ethanol-induced liver injury and insulin/IGF resistance, even in the context of continued high-level ethanol consumption.
Relative Entropy and Moment Problems

We consider the von Neumann entropy I(ρ:=-trace(ρlogρ) and the Kullback-Leibler-Umegaki distance S(ρ∥σ):=trace(ρlogρ-ρlogσ) as regularizing functionals in seeking solutions to multi-variable and multi-dimensional moment problems. We show how to obtain extrema for such functionals via a suitable homotopy and how to characterize all the solutions to moment problems. The range of possible applications includes the inverse problem of describing power spectra which are consistent with second-order statistics, measurement in classical thermodynamics as well as a quantum mechanics, as well as analytic interpolation encountered in modern robust control (cf.[6], [14], [15], [16], [17]).
Real-Time Program Synthesis from Specifications

Real-time systems are characterized by their umbilical connection to the environment [11]. They are most often modeled as event driven systems where the occurrence of events dictates a timed response by the system [3]. Such a behavior is naturally described by a state transition diagram [1], The goal of this paper is to initiate an algebraic methodology for real-time program development that is convenient for the programmer and allows easy proofs of the correctness of real-time programs. This methodology is algebraic in nature in the sense that program development is closer to the development of algebraic computations rather than to the development of programs using conventional languages. Following this methodology a real-time program is developed in two steps: first the behavior of a real-time system is specified using a real-time system specification language and then, this behavior is automatically transformed into a semantic driven automaton [9, 6] that implements the real-time program. Consequently, no programming activity in the usual sense is involved. A similar approach for real-time program development is described in [8]. The difference is that our real-time system specification language is a regular language on the alphabet of conditional-actions similar to guarded commands [4] while in [8] a language of timed processes [7] is used. In addition, the abstract time used to model the time is different in the two approaches.
Collaborative research in medical education: a discussion of theory and practice

CONTEXT Medical education researchers are inherently collaborators. This paper presents a discussion of theoretical frameworks, issues and challenges around collaborative research to prepare medical education researchers to enter into successful collaborations. It gives emphasis to the conceptual issues associated with collaborative research and applies these to medical education research. Although not a systematic literature review, the paper provides a rich discussion of issues which medical education researchers might consider when undertaking collaborative studies. METHODS Building on the work of others, we have classified collaborative research in three dimensions according to: the number of administrative units represented; the number of academic fields present, and the manner in which knowledge is created. Although some literature on collaboration focuses on the more traditional positivist perspective and emphasises outcomes, other literature comes from the constructivist framework, in which research is not driven by hypotheses and the approaches emphasised, but by the interaction between investigator and subject. DISCUSSION Collaborations are more effective when participants overtly clarify their motivations, values, definitions of appropriate data and accepted methodologies. These should be agreed upon prior to commencing a study. The way we currently educate researchers should be restructured if we want them to be able to undertake interdisciplinary research. Despite calls for researchers to be educated differently, most training programmes for developing researchers have demonstrated a limited, if not contrary, response to these calls. CONCLUSIONS Collaborative research in medical education should be driven by the problem being investigated, by the new knowledge gained and by the interpersonal interactions that may be achieved. Success rests on recognising that many of the research problems we, as medical educators, address are fundamentally interdisciplinary in nature. This represents a transition to bridge the dichotomy often presented in medical education between theory building and addressing practical needs.
Men Own the Fields, Women Own the Crops: Gender and Power in the Cameroon Grassfields

Men Own the Fields, Women Own the Crops: Gender and Power in the Cameroon Grassfields. Miriam Goheen. Madison: University of Wisconsin Press, 1996. 252 pp.
The supervision of psychotherapy supervisor trainees.

Much has been written about the needs of therapy trainees and how to address them in supervision, but little has been written about how to address the needs of psychotherapy supervisor trainees who...
Sequences of topotecan and cisplatin: phase I, pharmacologic, and in vitro studies to examine sequence dependence.

PURPOSEA phase I and pharmacologic study was performed to evaluate the feasibility of administering the topoisomerase I (topo I) inhibitor topotecan (TPT) in combination with cisplatin (CDDP) in minimally pretreated adults with solid tumors. The study was designed to evaluate the magnitude of the toxicologic and pharmacologic differences between the two sequences of drug administration.MATERIALS AND METHODSTPT was administered as a 30-minute infusion daily for 5 days and CDDP was given either before TPT on day 1 or after TPT on day 5. Each patient was treated with both schedules on an alternating basis every 3 weeks. Sequential dose escalation of TPT or CDDP resulted in three dosage permutation of TPT/CDDP (mg/m2): 0.75/50, 1/50, and 0.75/75. After the maximum-tolerated dose (MTD) level was achieved, the feasibility of using granulocyte colony-stimulating factor (G-CSF) to permit further dose escalation was studied. To examine the interaction of TPT and CDDP in vitro, human A549 lung cancer cells were exp...
Dual-Substrate Plate Diffusion Assay for Proteases

A plate diffusion assay for endopeptidases was developed. Proteases applied to plates containing 1% casein, 1% gelatin, and 1.5% agar caused distinct zones reminiscent of immunoprecipitation bands. The diameter of the zones was linearly proportional to the log of the enzyme activity applied over a range from 0.01 to greater than 100 IU/ml.
Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate

We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK) fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV) challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV), both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from 30%) and mortality (from 0 to 100%), CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality). These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.
A Factor Analysis of the Social Problem-Solving Inventory using Polychoric Correlations 1The participation of Albert Maydeu-Olivares in this research was supported by a Fulbright-La Caixa scholarship. Parts of this paper were performed by the first author as part of his doctoral dissertion at the University of Barcelona, directed by Juana Gómez Benito.

The Social Problem-Solving Inventory (SPSI; D'Zurilla & Nezu, 1990) is a theory-driven instrument that was designed to measure two major hypothesized components of the social problem-solving process: (1) problem orientation and (2) problem-solving proper. In the present study, factor analyses using polychoric correlations were performed on the total item pool of the SPSI and its two major scales and seven subscales to examine the construct validity of the theoretical model underlying this inventory. The results indicate that the SPSI is actually measuring two different kinds of problem orientation (positive and negative) and three different problem-solving styles (a rational/systematic problem-solving style, an impulsive/careless style, and an avoidant style).
Influence of Persistent Contaminants and Steroid Hormones on Glioblastoma Cell Growth

Glioblastoma multiforme (GBM), a malignancy characterized by its rapid progression, presents a lower risk of occurrence in women during their reproductive years. Necrosis of brain tissue during tumor invasion releases free lipids, and therefore might release contaminants stored in phospholipid-rich neuronal tissue. This study assesses the growth response of two human glioblastoma cell lines, T98G and U138-MG, treated with environmental chemicals known or likely to persist within the brain. Persistent chlorinated pesticides, industrial contaminants, persistant perfluorinated chemicals, and steroid hormones were assayed over a range of concentrations. Although cytotoxic effects were seen in both T98G and U138-MG cells, proliferative responses occurred only in the T98G cell line. Dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polychlorinated biphenyl (PCB) 153 were cytotoxic in both lines at 5000 nM. Perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and test...
Ferromagnetic Spin Fluctuation Induced Superconductivity in Sr 2 RuO 4

We propose a quantitative model for triplet superconductivity in ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}$ based on first principles calculations for the electronic structure and magnetic susceptibility. The superconductivity is due to ferromagnetic spin fluctuations that are strong at small wave vectors. The calculated effective mass renormalization, renormalized susceptibility, and superconducting critical temperature are all in good agreement with experiment. The order parameter is of comparable magnitude on all three sheets of the Fermi surface.
Morphometric aspects of the submucous plexus in whole-mount preparations of normal human distal colon

Abstract Background/Purpose: The diagnosis of intestinal neuronal dysplasia (IND) has traditionally been based on the finding of hyperplasia of the submucous plexus and increased acetyl-cholinesterase activity in parasympathetic nerve fibers in the lamina propria. However, recently it has been suggested that proposed diagnostic criteria relating to nerve cell density may overlap with age-related changes and that the finding of giant ganglia (ganglia containing more than seven ganglion cells) is the most relevant diagnostic parameter of IND. Ganglion cell counting is usually performed on conventional histological sections, whereas the topology of whole ganglia has been poorly studied. The aim of this study was to define the number of ganglion cells per ganglion and the ganglion cell density (the number of ganglion cells per surface area) in submucous whole-mount preparations of normal human colon. Methods: Specimens from distal colon were obtained during postmortem examination from 14 patients who died of nongastrointestinal disease. The submucous layer was prepared as a whole mount and stained for NADPH diaphorase (a nitrergic neurotransmitter marker) and cuprolinic blue (a general neuronal marker). Ganglion cell density was estimated by counting at least 10 mm 2 . The number of ganglion cells per ganglion was counted in at least 20 ganglia per case. Results: Ganglion cell density (NADPH diaphorase) fell markedly during the first 5 to 6 years of life (r = −0.60, P Conclusions: The density of NADPH diaphorase-positive ganglion cells in the submucous plexus of human distal colon decreases markedly with age. However, the number of ganglion cells per ganglion remains constant. These findings indicate that the age of the patient has crucial importance for the histolopathologic evaluation of enteric nervous system disorders.