cssi/SciSciGPT-SciSciNet huggingface dataset:
PARP Inhibition Induces Enrichment of DNA Repair–Proficient CD133 and CD117 Positive Ovarian Cancer Stem Cells

PARP inhibitors (PARPi) are FDA-approved monotherapy agents for the treatment of recurrent ovarian cancer in patients with and without a BRCA mutation. Despite promising response rates, not all patients derive benefit, and the majority develop resistance. PARPi treatment in vitro and in vivo induced an enrichment of CD133+ and CD117+ ovarian cancer stem cells (CSC). This effect was not affected by BRCA mutation status. In the CSC fractions, PARPi induced cell-cycle arrest in G2-M with a consequent accumulation of γH2AX, RAD51, and uniquely DMC1 foci. DNA damage and repair monitoring assays demonstrated that CSCs display more efficient DNA repair due, in part, to activation of embryonic repair mechanisms which involved the RAD51 homologue, DMC1 recombinase. Preserved and induced homologous repair (HR) could be a mechanism of an inherent resistance of CSCs to the synthetic lethality of PARPi that likely promotes disease recurrence. IMPLICATIONS: Treatment with PARPi fails to significantly affect ovarian cancer CSC populations, likely contributing to recurrent disease. Ovarian cancer CSCs stabilize genomic integrity after PARPi treatment, due to a more efficient inherent DNA repair capacity. PARPi-induced DMC1 recombinase and HR proficiency provide CSCs the opportunity to repair DNA damage more efficiently.Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/2/431/F1.large.jpg.
Interactive Analysis of Closed Loop Electro-hydraulic Control Systems

Without exhaustive system simulation, using full featured software, predicting electro-hydraulic control system performance represents a challenge for many system designers. In this paper, an introductory study has been presented as a preliminary stage for an ultimate goal, which is developing cost effective Interactive Electro-hydraulic Closed Loop System Analyzer (IEHCLSA). IEHCLSA is software aiming ultimately, through several modules in further developments, to solve for the static and dynamic characteristics of a controlled hydraulic actuator in a feedback loop fashion. This study shows in a systematic calculation approach how to properly calculate the pressure, flow and power required to achieve certain acceleration/deceleration rate while a cylinder is moving. The study will be associated with the first version of the software, which will be used to solve this part of the problem interactively. The following set of design parameters will be used as inputs to the stream of the calculations, the hydraulic cylinder dimensions, equivalent moving mass, volumes of the hydraulic lines, hydraulic fluid bulk modulus, required deceleration/acceleration rate and the external force distribution over the cylinder stroke. The calculation outcome will be hydraulic cylinder stiffness, natural frequency, flow and pressurerequirements. Using such software may reduce the effort, time and cost of hydraulic system prototyping.
Lightweight carbon nanotube surface thermal shielding for carbon fiber/bismaleimide composites

Abstract Carbon fiber reinforced polymers (CFRP) are becoming increasingly used in aerospace applications which require lightweight and stability at high temperatures. This paper discusses a systematic design of a carbon nanotube/phenolic thermal protection layer (TPL) with heat shield functionality while maintaining designed mechanical strength compared to traditional CFRP composites. These TPLs were integrated onto the surface of carbon fiber/bismaleimide composites to act as a heat shield for hybrid composites. A bonding layer of ultra-thin unidirectional carbon fiber was introduced between the TPLs and CFRP to improve the constituent interface. Hybrid composites with different TPL volume fractions were produced. The TPLs resulted in a 17% decrease of the through-thickness thermal conductivity for hybrid composites. A flame torch test was used to evaluate the thermal shield effectiveness, and the hybrid composites showed a noticeable increase in residual flexural strength and modulus when compared to the control samples under a heat flux of 20 W/cm2. The retention of the strength and modulus of the hybrid composites after burning was 39% and 70% of the initial value, respectively, as compared to 11% and 21% of the CFRP control. This paper also discusses the effects of TPLs’ coefficient of thermal expansion and protection mechanisms.
“I’ve never told anyone this, but...”: First Tellings of College-Aged Women’s Reproductive Healthcare Experiences

Telling a story for the first time is a profound experience for both a storyteller and story-listener. This essay describes the significance of first tellings as a narrative event that captures the complexities of the untold stories about young women's reproductive healthcare experiences. Additionally, this essay identifies the importance of first-told stories and explores how the storyteller and story-listener grapple with these narrative events. It also considers how first tellings may affect story-listeners' roles and influence storytellers' identity construction and framing strategies for subsequent tellings of the same story.
Microarray and RNA in situ hybridization assay for recurrence risk markers of breast carcinoma and ductal carcinoma in situ: Evidence supporting the use of diverse pathways panels

Breast tumor stratification by recurrence-risk is critical for deciding patient treatment. Here an approach combining cancer pathways microarray data complemented by RNA in situ hybridization (ISH) was investigated as a means for recurrence marker discovery and visualization in pathology specimens. LncRNA and mRNA expressions in breast carcinomas with low (n = 8) vs intermediate/high (n = 10) recurrence-scores as estimated by 21-gene assay and pathology review were compared by microarray assay. Tissue microarrays were prepared from breast carcinomas (n = 20) and ductal carcinoma in situ (DCIS) specimens (n = 84 patients) with known outcomes. Thirteen RNA ISH assays were performed: lncRNAs (BBC3-1, FER3, RAD21-AS1, ZEB1-2) and mRNAs (GLO1, GLTSCR2, TGFB1, TLR2) (implicated by the microarray data); MKI67; a pooled panel of recurrence-associated proliferation markers (BIRC5, Cyclin B1, MKI67, MYBL2, STK15); a pooled panel of non-proliferation recurrence-associated markers (CEACAM5, HTF9C, NDRG1, TP53, SLC7A5); and lncRNAs H19 and HOTAIR. Seven lncRNAs and 10 mRNAs showed significantly (P < .05) altered upregulation or downregulation by microarray assay: carcinoma RNA ISH staining did not mirror these patterns. HOTAIR staining was associated with a higher breast cancer recurrence score (P = .0152); qualitatively, H19 was massively expressed in a metaplastic triple negative breast carcinoma. Among the DCIS cohort, significant associations with multiple outcome variables were noted for TGFB1 and the non-proliferation panel (P-value range: .0001 to .047); proliferation panel staining showed an association with increasing DCIS grade (P = .0269) but not with outcomes. The findings support recurrence-risk estimation by the use of multi-marker panels that are representative of diverse cellular pathways rather than over-reliance on proliferation targets. H19, HOTAIR, and TGFB1 RNA ISH show potential for selective diagnostics.
Patterns of Care and Survival Comparison of Adult and Pediatric Wilms Tumor in the United States: A Study of the National Cancer Database.

Abstract Objective To describe and compare the management of WT and oncologic outcomes by patient age using a large national database. Methods The National Cancer Database was queried for patients with WT diagnosis from 2004 to 2013. Patients were grouped by age and compared: pediatric ( 35 years). Overall survival (OS) was the primary endpoint. Factors associated with OS were determined using multivariate analysis. Results The majority of patients were pediatric (n = 2686), followed by young adult (n = 91), and adult (n = 35). Five-year OS was significantly better for children vs young adults or adults (93.1% vs 79.1% vs 78.9%, respectively; P 15 years were less likely to undergo lymph node sampling (OR 0.19; P Conclusion Adults with WT experience worse 5- and 10-year OS when compared to children with WT. Survival decrements in adults are likely multifactorial including modifiable factors such as inadequate staging due to low rates of lymph node sampling, and underutilization of adjuvant therapies.
A Systematic Review of Nursing Home Palliative Care Interventions: Characteristics and Outcomes.

Abstract Background Despite recommendations to integrate palliative care into nursing home care, little is known about the most effective ways to meet this goal. Objective To examine the characteristics and effectiveness of nursing home interventions that incorporated multiple palliative care domains (eg, physical aspects of care—symptom management, and ethical aspects—advance care planning). Design Systematic review. Methods We searched MEDLINE via PubMed, Embase, CINAHL, and Cochrane Library's CENTRAL from inception through January 2019. We included all randomized and nonrandomized trials that compared palliative care to usual care and an active comparator. We assessed the type of intervention, outcomes, and the risk of bias. Results We screened 1167 records for eligibility and included 13 articles. Most interventions focused on staff education and training strategies and on implementing a palliative care team. Many interventions integrated advance care planning initiatives into the intervention. We found that palliative care interventions in nursing homes may enhance palliative care practices, including processes to assess and manage pain and symptoms. However, inconsistent outcomes and high or unclear risk of bias among most studies requires results to be interpreted with caution. Conclusions and Implications Heterogeneity in methodology, findings, and study bias within the existing literature revealed limited evidence for nursing home palliative care interventions. Findings from a small group of diverse clinical trials suggest that interventions enhanced nursing home palliative care and improved symptom assessment and management processes.
Mid-level constraint may correct coronal plane imbalance without compromising patient function in patients with severe osteoarthritis.

Abstract Introduction Mid-level constraint (MLC) in Total Knee Arthroplasty (TKA) offer surgeons the opportunity to obtain a well-balanced varus-valgus balance in the setting of slight ligament imbalance. As such, we sought to evaluate patient reported outcome measures (PROMs), alignment correction, and rate of revision between the MLC group and a cohort of posterior stabilized (PS) knees in a cohort of patients with preoperative degenerative arthritis. Materials/methods We performed a retrospective review of 57 MLC knees and 96 PS knees from a single manufacturer that were implanted by a single surgeon. We found the average age (68.91 vs. 68.40, p = 0.72), average BMI (30.88 vs. 29.14, p = 0.10), and gender breakdown (25:32 vs. 28:69, p = 0.08) to be comparable between the two cohorts. The latest follow-up was 4.0 years in the MLC group and 3.8 years in the PS group, p = 0.26. Results The two cohorts inherently resulted in significantly different preoperative deformities (MCL knees: average varus deformity 13.75°, average valgus deformity 12.37°; PS knees average varus deformity 15.14°, average valgus deformity 10.8°). There were more valgus knees in the MLC group (36 vs. 22 (p Conclusion/discussion This study demonstrated that the use of MLC in TKA allows surgeons to correct preoperative deformities with equal or improved functional outcomes compared to PS knees. In general, we recommend that surgeons try to balance the knee and use the least amount of constraint possible but should consider MLC when needed and use such implants if they are unable to balance the varus-valgus gap.
Theorizing Moral Cognition: Culture in Action, Situations, and Relationships:

Dual-process theories of morality are approaches to moral cognition that stress the varying significance of emotion and deliberation in shaping judgments of action. Sociological research that build...
Reliability of molecular dynamics interatomic potentials for modeling of titanium in additive manufacturing processes

Abstract We present an approach to study the transferability of molecular dynamics (MD) interatomic potentials (IPs) for materials modeling during metal additive manufacturing (MAM) processes, which involves rapid and cyclic melting, solidification, vaporization, and solid phase transformations. We apply the approach to the ten available IPs of titanium (Ti) as an example, which resembles the MAM process modeling of commercially pure Ti and Ti-base alloys. We consider the capability to produce solid phase change behavior of the alloy in equilibrium and nonequilibrium thermodynamics as the primary required characteristics of an IP for the MAM process modeling. Two-phase α-β, β-liquid, and liquid-vapor coexistence properties are used as the secondary criteria. Finally, we use other relevant single-phase properties as the tertiary criteria, such as the elastic constants at high temperatures, liquid structure factor, self-diffusivity, and shear viscosity. We show there are only three IPs that demonstrate reasonable characteristics for MAM process modeling.
Social Media for Mental Health: Data, Methods, and Findings

There is an increasing number of virtual communities and forums available on the web. With social media, people can freely communicate and share their thoughts, ask personal questions, and seek peer-support, especially those with conditions that are highly stigmatized, without revealing personal identity. We study the state-of-the-art research methodologies and findings on mental health challenges like depression, anxiety, suicidal thoughts, from the pervasive use of social media data. We also discuss how these novel thinking and approaches can help to raise awareness of mental health issues in an unprecedented way. Specifically, this chapter describes linguistic, visual, and emotional indicators expressed in user disclosures. The main goal of this chapter is to show how this new source of data can be tapped to improve medical practice, provide timely support, and influence government or policymakers. In the context of social media for mental health issues, this chapter categorizes social media data used, introduces different deployed machine learning, feature engineering, natural language processing, and surveys methods and outlines directions for future research.
Amygdala and Insula Connectivity Changes Following Psychotherapy for Posttraumatic Stress Disorder: A Randomized Clinical Trial

Abstract Background Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and biosignatures of therapeutic response. To this end, we assessed amygdala and insula treatment–related connectivity changes and their relationship to PTSD symptom improvements. Methods Individuals with a primary PTSD diagnosis (N = 66) participated in a randomized clinical trial of prolonged exposure therapy (n = 36) versus treatment waiting list (n = 30). Task-free functional magnetic resonance imaging was completed prior to randomization and 1 month following cessation of treatment/waiting list. Whole-brain blood oxygenation level–dependent responses were acquired. Intrinsic connectivity was assessed by subregion in the amygdala and insula, limbic structures key to the disorder pathophysiology. Dynamic causal modeling assessed evidence for effective connectivity changes in select nodes informed by intrinsic connectivity findings. Results The amygdala and insula displayed widespread patterns of primarily subregion-uniform intrinsic connectivity change, including increased connectivity between the amygdala and insula; increased connectivity of both regions with the ventral prefrontal cortex and frontopolar and sensory cortices; and decreased connectivity of both regions with the left frontoparietal nodes of the executive control network. Larger decreases in amygdala–frontal connectivity and insula–parietal connectivity were associated with larger PTSD symptom reductions. Dynamic causal modeling evidence suggested that treatment decreased left frontal inhibition of the left amygdala, and larger decreases were associated with larger symptom reductions. Conclusions PTSD psychotherapy adaptively attenuates functional interactions between frontoparietal and limbic brain circuitry at rest, which may reflect a potential mechanism or biosignature of recovery.
Civic Engagement and Community Heterogeneity: An Economist's Perspective

Now many of them [economists] are writing about neighborhood get-togethers, PTAs, Bible study classes, and the like …. This is not necessarily a good thing.—Claude S. Fischer, “Bowling Alone: What's the Score?”The authors thank the participants in the Conference on Social Connectedness and Public Activism (Harvard University), where an earlier version of this article was delivered in May 2002; Jennifer Hochschild; and four anonymous reviewers for comments. They also thank NIH grant R01 AG19637. Additionally, Dora Costa thanks NIH grants AG12658 and AG10120.
Surgical Outcomes for Accessory Navicular in Adolescent Athletes

Introduction: An accessory navicular is a plantar medial enlargement of the navicular bone of the foot. The accessory navicular is incorporated with the posterior tibial tendon which inserts into the navicular tuberosity. Patients with an accessory navicular present with a foot bump. This condition occurs in up to 12% of the population. Only some patients are symptomatic. The purpose of this study is to report the surgical outcomes in a consecutive series of adolescent athletes with symptomatic accessory navicular. Methods: The study was approved by the College of Medicine IRB. …
Subretinal Rather Than Intravitreal Adeno-Associated Virus-Mediated Delivery of a Complement Alternative Pathway Inhibitor Is Effective in a Mouse Model of RPE Damage.

Purpose The risk for age-related macular degeneration has been tied to an overactive complement system. Despite combined attempts by academia and industry to develop therapeutics that modulate the complement response, particularly in the late geographic atrophy form of advanced AMD, to date, there is no effective treatment. We have previously demonstrated that pathology in the smoke-induced ocular pathology (SIOP) model, a model with similarities to dry AMD, is dependent on activation of the alternative complement pathway and that a novel complement activation site targeted inhibitor of the alternative pathway can be delivered to ocular tissues via an adeno-associated virus (AAV). Methods Two different viral vectors for specific tissue targeting were compared: AAV5-VMD2-CR2-fH for delivery to the retinal pigment epithelium (RPE) and AAV2YF-smCBA-CR2-fH for delivery to retinal ganglion cells (RGCs). Efficacy was tested in SIOP (6 months of passive smoke inhalation), assessing visual function (optokinetic responses), retinal structure (optical coherence tomography), and integrity of the RPE and Bruch's membrane (electron microscopy). Protein chemistry was used to assess complement activation, CR2-fH tissue distribution, and CR2-fH transport across the RPE. Results RPE- but not RGC-mediated secretion of CR2-fH was found to reduce SIOP and complement activation in RPE/choroid. Bioavailability of CR2-fH in RPE/choroid could be confirmed only after AAV5-VMD2-CR2-fH treatment, and inefficient, adenosine triphosphate-dependent transport of CR2-fH across the RPE was identified. Conclusions Our results suggest that complement inhibition for AMD-like pathology is required basal to the RPE and argues in favor of AAV vector delivery to the RPE or outside the blood-retina barrier.
C-reactive Protein Levels in Plasma and Chronic Venous Ulcer Exudate of Persons Who Inject Drugs: A Pilot Study.

BACKGROUND Persons who inject drugs (PWID) in the groin, legs, and/or feet are at high risk for chronic venous ulcers (CVUs). The plasma C-reactive protein (CRP) level is a marker of systemic inflammation. OBJECTIVE This pilot study examined CRP levels in plasma and CVU exudate of PWID. The aims were to (1) compare levels of CRP in plasma and exudate; (2) examine if the CRP level in exudate changed over 4 weeks with wound treatment; and (3) examine the relationship of the exudate CRP level with CVU area, CVU age, number of CVUs, and number of comorbidities. MATERIALS AND METHODS Persons who inject drugs seeking wound care were enrolled in this Institutional Review Board approved prospective, longitudinal, descriptive study. A blood sample was collected on the first visit (week 1); the plasma was then separated. Wound exudate was collected on swabs during the first visit (week 1) and 4 weeks later (week 4). All samples were stored at -80° C. Samples were eluted from swabs using mass spectrometry grade water then aliquoted for CRP analysis. RESULTS The participants of the study included 14 PWID (mean age, 62.14 ± 4.52 years; mean number of comorbidities, 5.71 ± 1.90; and mean number of ulcers 2.07 ± 1.07 that were present for a mean of 7.96 ± 11.91 years without healing). C-reactive protein level in plasma was a mean of 6.47 ± 8.56 mg/L, with lower levels found in wound exudate but highly correlated (rho = .925). Exudate CRP levels decreased from week 1 to week 4, and the 2 were highly correlated (rho = .895). Exudate CRP level week 1 was not significantly related to wound area, wound age, number of ulcers, or number of comorbidities. CONCLUSIONS Plasma and exudate CRP levels were highly correlated. Exudate CRP levels decreased across time. Future large-scale wound healing studies should examine CRP levels over a longer duration and as they correlate to wound healing.
Localized hair loss in infancy: a review.

PURPOSE OF REVIEW The current review will address the different causes of localized hair loss in infancy. The data presented here will provide clinicians with the latest understanding of different disorders leading to localized hair loss and will provide recommendations for further management of infants who present with alopecia. RECENT FINDINGS Localized hair loss in infancy is common, but its underlying causes vary greatly. Alopecia in infants can be categorized into congenital, genetic, inflammatory, mechanical, and physiologic causes. Decisions regarding further management are complex, as they often involve not only cosmetic concerns, but also work-up of possible systemic medical issues related to hair loss. SUMMARY Clinicians must be able to distinguish between the different causes of infantile hair loss so that appropriate work-up and further management can be pursued. Factors such as physical appearance, timing of presentation, dermoscopic exam, histopathology, and associated systemic features can help lead clinicians to the correct diagnosis in the case of an infant with localized alopecia.
Impact of COVID-19 on a Pragmatic, Cluster Randomized Clinical Trial for Fibromyalgia

Our objective was to present our experience on adapting to the challenges of COVID-19 pandemic on a pragmatic clinical trial. Transcutaneous Electrical Nerve Stimulation (TENS) in Physical Therapy (PT) Study (FM-TIPS) is a pragmatic, cluster-randomized clinical trial examining if the addition of TENS to routine PT improves movement-evoked pain in fibromyalgia (FM). FM patients (n=600) were enrolled from 24 PT clinics (12 PT only, 12 PT with TENS) across five healthcare systems. COVID-19 has significantly impacted PT practice and in-person interactions. In response, all PT clinics saw reduced volumes of patients, some clinics furloughed PTs, and some clinics were permanently closed. This led us to put contracts, reliance agreements, and training of clinics on hold and to seek additional clinics that could fill the gap for those who could no longer participate. It also led to a delay in onboarding healthcare systems and inpatient enrollment. In order to protect the integrity of the study and minimize missing data due to potential restrictions of in-person visits we developed alternative strategies. This includes procedures for home instruction of TENS via telehealth, a plan for bringing on backup clinics, and a plan for training virtually and in-person using personal protective equipment and social distancing. Assessment of primary outcome and questionnaire data were transitioned for the patient to perform at home through a patient-portal with embedded patient-specific videos. We have also set up a phone line for patients to call with additional questions or concerns. The impact of COVID-19 on statistical design and analysis was discussed including a plan for uneven enrollment across clinics and a sub-analysis of data for patients enrolled during or after the pandemic. In conclusion, COVID-19 altered the original study design of this large-pragmatic trial to account for greater flexibility for providers and patients to facilitate continued enrollment. NIH.
Understanding the Limits of Sub-diffraction Focusing of Light with Photonic Funnels

We analyze, numerically and experimentally, deep subwavelength focusing of light in new material platform, photonic funnels, implemented at infrared frequencies with semiconductor-based hyperbolic metamaterials, as function of material concentration, geometric profile, and cladding characteristics.
Orthogonal control of gene expression in plants using synthetic promoters and CRISPR-based transcription factors

Background: The construction and application of synthetic genetic circuits is frequently improved if gene expression can be orthogonally controlled, relative to the host. In plants, orthogonality can be achieved via the use of CRISPR-based transcription factors that are programmed to act on natural or synthetic promoters. The construction of complex gene circuits can require multiple, orthogonal regulatory interactions, and this in turn requires that the full programmability of CRISPR elements be adapted to non-natural and non-standard promoters that have few constraints on their design. Therefore, we have developed synthetic promoter elements in which regions upstream of the minimal 35S CaMV promoter are designed from scratch to interact via programmed gRNAs with dCas9 fusions that allow activation of gene expression. Results: A panel of three, mutually orthogonal promoters that can be acted on by artificial gRNAs bound by CRISPR regulators were designed. Guide RNA expression targeting these promoters was in turn controlled by either Pol III (U6) or ethylene-inducible Pol II promoters, implementing for the first time a fully artificial Orthogonal Control System (OCS). Following demonstration of the complete orthogonality of the designs, the OCS was tied to cellular metabolism by putting gRNA expression under the control of an endogenous plant signaling molecule, ethylene. The ability to form complex circuitry was demonstrated via the ethylene-driven, ratiometric expression of fluorescent proteins in single plants. Conclusions: The design of synthetic promoters is highly generalizable to large tracts of sequence space, allowing Orthogonal Control Systems of increasing complexity to potentially be generated at will. The ability to tie in several different basal features of plant molecular biology (Pol II and Pol III promoters, ethylene regulation) to the OCS demonstrates multiple opportunities for engineering at the system level. Moreover, given the fungibility of the core 35S CaMV promoter elements, the derived synthetic promoters can potentially be utilized across a variety of plant species.
DDT and inflammatory responses: 3. Release of histamine from mast cells exposed to DDT

Abstract Release of histamine from mast cells by DDT was demonstrated by incubating guinea pig mesentery explants with 20 μg DDT/ml in vitro for various periods up to 2 hr. The histamine content of mesentery explants showed progressive decreases concomitant with increasing histamine values in the incubation medium. In the mesentery explants the histamine content decreased to 31% of the original content within 45 min and then increased to 113% at the 120-min interval. As the total amount of histamine released into the medium during the 2 hr of incubation with DDT was twice the original amount of histamine in the tissues, it is evident that the initial release of histamine by DDT stimulates its resynthesis in the mast cells.
Lifting Techniques For Mixed Integer Programming

This article provides a review of lifting techniques for the generation of cutting planes in mixed integer programming. After motivating the notion of lifting graphically, four key steps in the derivation of lifted inequalities are described: (i) variables fixing, (ii) derivation of seed inequalities, (iii) (re-)computation of lifting functions, and (iv) derivation of lifting coefficients. Practical considerations that are relevant to each of these steps are discussed and is emphasized the importance of superadditivity in designing efficient lifting procedures. This concluded with a description of the strength of lifted cuts. Throughout, concepts on a simple example are illustrated. Keywords: mixed integer programs; cutting planes; facet; lifting techniques; superadditive lifting
DNA from copulatory plugs can give insights into sexual selection

Copulatory plugs serve as mating barriers in many animal species. We collected plugs and vaginal swabs from female banner-tailed kangaroo rats Dipodomys spectabilis in a wild population with all males individually genotyped, and used them as a source of DNA. Copulatory plugs solidly filled the reproductive tract, including the entrances to the uterine horns. Contrary to the popular hypothesis that plugs prevent females from remating, these plugs surprisingly contained DNA from up to three males. Alleles contributed by males were more numerous in internal sections of the plugs. Our results confirm that D. spectabilis females mate with multiple males and suggest that they avoid mating with close relatives. The apparent underrepresentation of DNA from related males implies precopulatory sexual selection, but postcopulatory mechanisms may also be at work. For example, our data are consistent with the possibility that pressure generated during plug coagulation promotes movement of sperm beyond cervical barriers. In controlled experimental settings, DNA from plugs will provide a powerful tool for distinguishing pre- and postcopulatory sexual selection.
A model for assessing the effects of communication on recreationists.

This study proposes a model of persuasion for evaluating informational techniques used in recreation management. The model focuses on the communication response process and factors which influence ...
On sample-based implementation of non-smooth decision fusion functions

A number of optimal fusion functions have been derived in the literature for multiple detection systems based on a complete knowledge of the detector distributions. In several practical systems, however, only measurements are available. A general result was recently shown that any fusion function with a suitable Lipschitz property derived under the complete knowledge of the distributions can be converted into a measurement-based one. While this result subsumes the well-known cases of independent and correlated detectors, it is not applicable to discontinuous fusion rules which often arise in practice. In this paper, we show that any fusion function with bounded variation can be converted into a measurement-based one with a somewhat weaker guarantee. These fusion functions subsume Lipschitz as well as several discontinuous fusion functions. In particular we show that given a sufficiently large sample, the measurement-based fusion function performs almost as well as the optimal one with an arbitrarily specified confidence.
Generalized information theory

Abstract Generalized information theory is viewed in this paper as an information theory that is liberated from the boundaries of probability theory. After overviewing classical (probabilistic) information theory, the paper examines recent developments regarding nonprobabilistic measures and principles of uncertainty-based information, which form a nucleus of the emerging generalized information theory.
Salvage/adjuvant brachytherapy after ophthalmic artery chemosurgery for intraocular retinoblastoma.

Purpose To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. Methods and Materials This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Results Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less ( P =.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Conclusions Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG.
Genetic heterogeneity and cancer drug resistance

Despite the success of targeted therapies in the treatment of cancer, the development of resistance limits the ability to translate this method into a curative treatment. The mechanisms of resistance have traditionally been thought of as intrinsic (ie, present at baseline) or acquired (ie, developed after initial response). Recent evidence has challenged the notion of acquired resistance. Although cancers are traditionally thought to be clonal, there is now evidence of intra-tumour genetic heterogeneity in most cancers. The clinical pattern of acquired resistance in many circumstances represents outgrowth of resistant clones that might have originally been present in the primary cancer at low frequency but that have expanded under the selective pressure imposed by targeted therapies. Here, we describe the potential role of clonal heterogeneity in resistance to targeted therapy, discuss genetic instability as one of its causes, and detail approaches to tackle intra-tumour heterogeneity in the clinic.
H3: laying out large directed graphs in 3D hyperbolic space

We present the H3 layout technique for drawing large directed graphs as node-link diagrams in 3D hyperbolic space. We can lay out much larger structures than can be handled using traditional techniques for drawing general graphs because we assume a hierarchical nature of the data. We impose a hierarchy on the graph by using domain-specific knowledge to find an appropriate spanning tree. Links which are not part of the spanning tree do not influence the layout but can be selectively drawn by user request. The volume of hyperbolic 3-space increases exponentially, as opposed to the familiar geometric increase of euclidean 3-space. We exploit this exponential amount of room by computing the layout according to the hyperbolic metric. We optimize the cone tree layout algorithm for 3D hyperbolic space by placing children on a hemisphere around the cone mouth instead of on its perimeter. Hyperbolic navigation affords a Focus+Context view of the structure with minimal visual clutter. We have successfully laid out hierarchies of over 20,000 nodes. Our implementation accommodates navigation through graphs too large to be rendered interactively by allowing the user to explicitly prune or expand subtrees.
Group desistance from terrorism: A dynamic perspective

This paper examines recent efforts to conceptualize group-level desistance from terrorism, identifies relevant actors and actions in the competition of terrorist groups and the governments they target, and identifies the multiple forms of desistance that can emerge from this competition. This dynamic model of terrorist and state competition then informs consideration of the three preceding papers in this issue of Dynamics of Asymmetric Conflict. The review of criminal desistance by LaFree and Miller highlights the importance of distinguishing individual desistance from group desistance and the wide appeal of rational choice models in criminology. The case studies of terrorist group desistance by Wheatley and McCauley (Egyptian Islamic Group) and by Dugan et al. (the Armenian Secret Army for the Liberation of Armenia and the Justice Commandos of the Armenian Genocide) show that terrorist sympathizers and supporters sometimes generalize from one terrorist group's mistakes to disapproval of terrorism as a ta...
Effect of adjuvant trastuzumab among patients treated with anti-HER2-based neoadjuvant therapy.

To study the impact of adjuvant trastuzumab among patients achieving a pathologic complete response (pCR) after trastuzumab-based neoadjuvant systemic therapy (NST). Patients with primary HER2-positive breast cancer treated with trastuzumab-based NST were categorised according to adjuvant trastuzumab administration and pCR status. Adjuvant trastuzumab became standard of care in 2006, this was the main reason patients in our cohort did not receive adjuvant trastuzumab. Kaplan–Meier was used to estimate survival. A test for interaction between adjuvant trastuzumab and pCR was completed. Of 589 patients, 203 (34.5%) achieved a pCR. After surgery, 109 (18.5%) patients in the entire cohort did not receive adjuvant trastuzumab. Among patients achieving a pCR, 31.3% received adjuvant trastuzumab compared with 68.8% among those who did not achieve a pCR (P=0.0006). Among patients achieving pCR, adjuvant trastuzumab did not further improve overall survival (OS) or relapse-free survival (RFS) (P=0.35 and P=0.93, respectively). Any benefit of adjuvant trastuzumab in OS and RFS among patients without a pCR did not achieve statistical significance (P=0.3 and P=0.44, respectively). In this cohort, patients treated with trastuzumab-based NST who achieved a pCR have excellent outcome regardless of whether they received adjuvant trastuzumab.
Simultaneous observation of NMR spin noise and maser spontaneous emission

Abstract Spin noise emission, absorbed noise, and spontaneous maser emission are distinguished in the hexanol molecule by changing spin noise dynamics along with coupling the spin system to a probe circuit. Inverted magnetization leads to spontaneous maser emission of methyl and methylene resonances permitting separation from broad overlapped peaks. The maser emission resonance shows random intensity the scattering range of which depends on the length of the gradient following magnetization inversion. Combination of thermal noise and spin noise can be altered by varying magnetization orientation. This results in radiation damping which alters how fluctuation signals are coupled with the probe circuit.
Smaller is better? [micromotors and electric drives]

Some fundamental constraints on the performance of micromotor technology have been discussed. Several aspects of performance were explored, including energy density, force density, size, constraints on motor-drive circuitry, motor topologies, and friction. Analysis shows that electrostatic machines have advantages as microfabrication processes achieve finer resolution, and, in fact, can exceed the energy and force density capabilities of conventional magnetic machines at small enough scales. Major thrusts for electric drive theory to be applied are in control, topology optimization, and machine testing.
Genomic risk of hepatitis C-related hepatocellular carcinoma

To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P <1 10(⁻5)) in the genome-wide association study were further genotyped in 673 cases and 2596 controls. We found a previously unidentified locus in the 50 flanking region of MICA on 6p21.33 (rs2596542, P(combined) = 4.21 10(⁻13), odds ratio = 1.39) to be strongly associated with HCV induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 10(⁻8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 10(⁻13)).
Paper 15: The Design of Tubular Gas Turbine Combustion Chambers for Optimum Mixing Performance:

A method is presented for determining the ideal ratio of flame-tube diameter to air-casing diameter, and the optimum number and size of dilution holes, for the attainment of a well-mixed primary co...
Using modelled stream temperatures to predict macro-spatial patterns of stream invertebrate biodiversity

Summary Stream temperature is thought to be a primary determinant of the macro-spatial distribution of stream biota, but we lack temperature data for most streams. Past research often relied on surrogates, such as altitude, latitude, catchment area (ALCA) and air temperature to study biota–temperature relationships. However, temperature surrogates may not accurately represent the thermal environments experienced by the biota and could thus produce misleading inferences regarding such relationships. In the absence of observations, modelled stream temperature could improve both predictions and interpretations of stream biodiversity patterns. We tested this hypothesis by relating stream benthic invertebrate assemblage structure and composition at 92 reference-quality streams to ALCA, air temperature, modelled stream temperature and measured stream temperature, that is a progression from a coarse surrogate to directly measured water temperature. Modelled stream temperatures were obtained from a U.S.A.-wide model developed previously with data from 569 reference-quality sites. Variation in taxonomic composition, measured with an ordination, was strongly and almost identically associated with both modelled and measured stream temperature, but was less strongly associated with ALCA and air temperature. We also built predictive niche models to assess how choice of thermal metrics affected model performance. Model performance was measured as the precision with which each model predicted the number of taxa at a site (i.e. observed-to-expected taxon ratios). Niche models that contained modelled or measured stream temperature were more precise than those based on air temperature and ALCA. In addition, we compared the predicted probabilities of occurrence using niche models based on both modelled and measured stream temperatures. The two produced predicted probabilities of occurrence that were statistically indistinguishable for most (79%) taxa. Finally, we calculated thermal optima for each taxon as the abundance-weighted average of stream temperature at sites where each taxon occurred. Thermal optima produced with modelled and measured stream temperatures were almost identical. Large-scale models of stream temperature can be sufficiently accurate and precise to detect temperature-driven patterns in stream biodiversity and should be useful in predicting the effects of climate change and other human-caused thermal alterations on stream biodiversity.
Studying ourselves: Sociology discipline-building in the United States

self-studies, internal evaluations, and in the various histories of the discipline and of its professional organizations. In the early years of discipline-building, those who were, or wanted to be, sociologists studied themselves prodigiously and attempted to chart a course for posterity Prompted by the centennial anniversary of the American Sociological As sociation in 2005, it is timely to look back at how we defined and studied ourselves and at what was said as well as what was left unsaid. The "fathers" of American sociology and their network of associates engaged in dis cipline-building as they studied and directed the progress of the new science of sociol ogy. They collected data, analyzed it, reported their findings at professional meetings, and published them in the prominent journals of the day Of particular interest is who documented the history of early American sociology, how, and why? Peter Baehr di chotomized contributions to the development of sociology as either discursive or institu tional. Discursive contributions are those of ideas, and institutional those establishing "some artifact or institution demonstrably related to the sociological enterprise" (2002: 6). This work deals with the latter, specifically with sociology in institutions of higher education in the United States as it was introduced, defined, measured, and publicly presented. As is evident in the literature, the early history of academic sociology was written by white males and focused on selected male and coeducational institutions. In addition to looking at that history as a sociology of sociology, we will also seek out and examine the treatment of the "special mission" institutions for women and for blacks
The deformation and retraction of thermotropic LCP droplets in a flexible polymer matrix

We have studied the initial deformation and shape recovery of droplets of a flexible polymer and a liquid crystalline polymer in a flexible thermoplastic matrix. The LCP droplets exhibit a size dependence that is not observed for the flexible polymer droplets, possibly because of the effect of orientational elasticity in the liquid crystalline polymer.
Abstract 5031: Combination inhibition of the FAK-p53 and MDM2-p53 interactions suppressed proliferation in mesothelioma

Mesothelioma is a chemotherapy-resistant neoplasm, as is evident in the dismal survival for patients with this asbestos-associated disease. Conventional chemotherapies and radiation therapy have only limited efficacy, and improved survival will require development of novel and more effective pharmacological interventions. Although p53 genomic mutations are uncommon in mesothelioma, we hypothesized that functional p53 inactivation (resulting from NF2-dysregulated FAK activation) might be a frequent event. Using proteomic methods, with tandem mass spectrometry analyses of mesotheliomas after double immuno-affinity purifications for p53 and phosphotyrosine, we find that FAK is consitutively activated in 10 of 10 mesothelioma cell lines and 9 of 9 mesothelioma surgical specimens, and associated with p53 in 6 of 6 mesothelioma cell lines. In four mesotheliomas with non-mutant p53, FAK silencing by lentiviral short hairpin RNA (shRNA) induced expression and phosphorylation of p53 at Ser15. However, FAK regulation of mesothelioma proliferation was not restricted to p53-dependent pathways, as demonstrated by immunoblots after FAK knockdown in JMN1B mesothelioma cells, which have mutant/inactivated p53, compared to MESO924, MESO257, MESO296, and MESO428 cells, which have nonmutant p53. Additive effects were obtained through a coordinated attack on p53, as demonstrated by immunoblots, cell viability and cell cycle analyses, showing that FAK knockdown and MDM2 inhibition (nutlin-3) induced greater p53 expression, cell apoptosis, anti-proliferative effects and cell cycle arrest, compared to either intervention alone. These findings highlight novel therapeutic opportunities in mesothelioma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5031.