cssi/SciSciGPT-SciSciNet huggingface dataset:
Design Elegance and Systems Engineering

The term “elegance” is typically associated with aesthetics. In complex systems design, elegance is what separates the merely functional from the truly engaging. An elegant design is often inspired by a theme that drives its creation. It engages users and encourages exploration. The process of elegant system design is a creative process that focuses on the total experience and exploits systems thinking, probing and questioning, and the use of appropriate analogies and metaphors to simplify system architecture and design by eliminating extraneous constraints that can show up with poor problem framing. This chapter presents the characteristics of elegant design and the attributes of elegant system designers. It stresses the importance of smart questions, metaphors, and analogies in creating elegant designs. It presents a heuristics-enabled elegant design approach along with quantitative and qualitative metrics to users' elegance. It concludes with a call to pursue research in this relatively nascent, high-payoff design thrust.
Toward a Documentary History of American Women Mathematics PhDs: The Doctoral Classes of 1940–1959

In 1993, I started to compile a database of biographical information on the roughly 200 women who earned PhDs in mathematics from US colleges and universities during the 1940s and 1950s. At the time, my primary motivation was to locate and interview as many of those still living as I reasonably could. My book, Women Becoming Mathematicians (MIT Press 2000)—while providing an overview of the entire group—was devoted in the main to what I had learned by conducting oral history interviews with 36 of the women. In recent years, I have returned to the task of completing the database and publishing it online. In this essay, I describe the personal motivations that led me to this project, surprises that emerged in the course of my research, and my ongoing efforts to complete and publish the database. In light of the trailblazing work of Green and LaDuke on the pre-1940 doctorates, and the project of Leggett and Case on PhDs of the 1960s and 1970s, I see this work as key to a larger program of compiling a documentary history of the first century of American women mathematics PhDs.
Antimicrobial blue light inactivation of biofilms formed by clinical isolates of multidrug-resistant microorganisms

Antibiotic resistance is one of the most serious threats to public health. It is estimated that at least 23,000 people die each year in the USA as a direct result of antibiotic-resistant infections. In addition, many antibiotic-resistant microorganisms develop biofilms, surface-associated microbial communities that are extremely resistant to antibiotics and the immune system. A light-based approach, antimicrobial blue light (aBL), has attracted increasing attention due to its intrinsic antimicrobial effect without the involvement of exogenous photosensitizers. In this study, we investigated the effectiveness of this non-antibiotic approach against biofilms formed by multidrug-resistant (MDR) microorganisms. MDR Acinetobacter baumannii, Escherichia coli, Candida albicans, and Pseudomonas aeruginosa biofilms were grown either in 96-well microtiter plates for 24 h or in a CDC biofilm reactor for 48 h, and then exposed to aBL at 405 nm emitted from a light-emitting diode (LED). We demonstrated that, for the biofilms grown in the CDC biofilm reactor, approximately 1.88 log10 CFU reduction was achieved in A. baumannii, 2.78 log10 CFU in E. coli and 3.18 log10 CFU in P. aeruginosa after 162 J/cm2 , 576 J/cm2 and 500 J/cm2 aBL were delivered, respectively. For the biofilms formed in the 96-well microtiter plates, 5.67 and 2.46 log10 CFU reduction was observed in P. aeruginosa and C. albicans polymicrobial biofilm after an exposure of 216 J/cm2 . In conclusion, aBL is potentially an alternative non-antibiotic approach against MDR biofilm-related infections. Future studies are warranted to investigate other important MDR microorganisms, the mechanism of action of aBL, and aBL efficacy in vivo.
Influences on Vietnamese Consumers’ Preference for US Clothing Brands

Vietnam is one of the most attractive markets in the world with their fast-growing middle class and increasing purchasing power. It is predicted that the middle class will be tripled in Vietnam between 2012 and 2020 (“Vietnamese Consumers”, 2013). Vietnamese consumers are buying more sophisticated products. For example, urban Vietnamese women aged between 20 and 45 spend 18% of their monthly income on apparel (Breu, Salsberg and Tu, 2010). The majority of emerging market consumer studies investigate the two of the world’s largest emerging markets, China and India.
Increasing the area of a white scattering background can increase the power output of a luminescent solar concentrator

Abstract Luminescent solar concentrators (LSCs) have the potential of converting solar energy into electricity more cheaply than a standard photovoltaic (PV) panel. LSCs are thin plates of plastic or glass that contain fluorescent material throughout the plate or in a thin film adhered to the surface. The fluorescent material absorbs sunlight and its fluorescence is concentrated onto PV cells along the edges of an LSC using total internal reflection. Some light is able to pass through the LSC and does not reach the PV cells. A white diffusive scattering surface, or white background, is able to scatter this light back into the LSC for another chance of reaching the PV cells. The results of our experimental and theoretical research reveal that using white backgrounds larger than the area of the LSC can further increase its power output. Larger backgrounds produce more power, but with diminishing returns. An optimal air gap between the LSC and a larger white background is required to achieve maximum benefit. The size of this optimal air gap increases as the area of the white background increases. The predictions of our theoretical model agree with our experimental results for the relative performance of these larger white backgrounds with respect to their size and separation from the LSC. Our experimental results show an optimal air gap of 10.7 cm separating an LSC from a white background with an area 16 times larger than the LSC. In this configuration, the LSC produced 28% more power than the maximum power output of the LSC using a white background of the same area, and 54% more power than the LSC with no white background present.
Attenuation of postischemic reperfusion injury is related to prevention of [Ca2+]m overload in rat hearts.

Intracellular calcium overload has been implicated in postischemic reperfusion injury. In myocytes, mitochondrial free calcium concentration ([Ca2+]m), not cytosolic free calcium concentration ([Ca...
Direction-of-Arrival Estimation with Diversely Polarized Sparse Arrays

Thinned arrays provide larger apertures and consequently better resolution than fully populated arrays with the same number of antennas. Sparse arrays, such as Minimum Redundancy Arrays (MRA), coprime arrays and nested arrays, are a subclass of thinned arrays. They are designed to have coarrays corresponding to a larger (virtual) uniform linear array. By exploiting the coarray structure the MUSIC algorithm can be applied to identify more signals than the number of antennas in the array. The work on sparse arrays as well as much of the work on thinned arrays assumes that the antennas are isotropic or omnidirectional and that there is no mutual coupling nor sensitivity to signal polarization. In this paper we study the impact of coupling and polarization on these arrays.
Serous macrophages pack Bhlhe40 for a randonnée

The transcription factor Bhlhe40 is required for the homeostatic proliferation of peritoneal macrophages and their expansion during type 2 immunity.
Quasi-Bayesian estimation of large Gaussian graphical models

Abstract This paper deals with the Bayesian estimation of large precision matrices in Gaussian graphical models. We develop a quasi-Bayesian implementation of the neighborhood selection method of Meinshausen and Buhlmann (2016). The method produces a product-form quasi-posterior distribution that can be efficiently explored by parallel computing. Under some restrictions on the true precision matrix, we show that the quasi-posterior distribution contracts in the spectral norm at the rate of O { s ⋆ ln ( p ) ∕ n } , where p is the number of nodes in the graph, n the sample size, and s ⋆ is the maximum degree of the undirected graph defined by the true precision matrix. We develop a Markov Chain Monte Carlo algorithm for approximate computations, following an approach from Atchade (2019). We illustrate the methodology using real and simulated data examples.
Life Between Patches: Incorporating Microbiome Biology Alters the Predictions of Metacommunity Models

Although most models conceptualize a metacommunity as a collection of habitat patches embedded in a matrix that is not hospitable to life, new applications of metacommunity theory to host-microbiome systems have shown this assumption to be flawed. Frequently the matrix is at least somewhat hospitable to the species that normally reside in the habitat patches. We modify an existing patch dynamic metacommunity model to incorporate the possibility of a hospitable matrix and expand the process of dispersal to include moving out of the patch, surviving/growing in the matrix, and moving into a new patch. With these alterations, we find that it is substantially harder for a dispersal specialist to persist in a system with a hospitable matrix compared to an inhospitable matrix. In addition, we find that the traits required to successfully disperse in the hospitable system are different from those required in the inhospitable system. The difference in dispersal traits in a hospitable environment versus an inhospitable one could be especially of interest to host-microbiome systems where manipulation of the matrix is common practice. For example, ventilation or disinfection of built environments is a common way to change the matrix properties for metacommunities of human or animal-associated microbiomes. We conclude that the qualities of the matrix can have important effects on community assembly, and that relaxing matrix assumptions broadens the range of applications for metacommunity ecology, including its use for host-microbe systems.
Romantic female friendships as resistance: subversive web series in the United States and India

The current representative wave of romantic female friendships (Girls, Broad City, Insecure) in the United States owes a great deal to the web series. The online platform bypasses conventions of th...
The Mysteries of Breath: What Do We Need and How Do We Teach It?

iv Introduction 1 Chapter 1: What Is Breath? 6 Chapter 2: Arthur Lessac 12 Chapter 3: Patsy Rodenburg 21 Chapter 4: Kristin Linklater 29 Chapter 5: Catherine Fitzmaurice 36 Chapter 6: F.M. Alexander 45 Chapter 7: Jo Estill 55 Chapter 8: How Do We Teach Breath? 63 Conclusion 69 Bibliography 71 Vita 73
Knowledge and Practice of Harm Reduction Strategies Among People Who Report Frequent Cannabis Use

We examined knowledge and practice of harm reduction strategies among people who use cannabis attending an annual public cannabis advocacy event. We also assessed the sources from which they glean ...
Child Rights in the United States: Dilemmas and Questions

Little scientific research has been done on child rights implementation or instruction at any level of education, preschool through university, in United States (US). Direct and unambiguous references to child rights are nearly invisible in American social, political, and educational discourses, though some related concepts, such as equality and inclusion, sometimes appear. The US remains the only United Nations Member State that has not ratified the Convention on the Rights of the Child (UNCRC). Despite strong emphasis on equality and rights in the country’s founding documents, life circumstances vary dramatically for its children due to such well-entrenched factors as (1) primacy of state governance over national governance; (2) lack of far-reaching national child policies, regulations, and funding; (3) wide disparities in children’s socioeconomic status, often correlated with significant, long-lasting disadvantages for racial and ethnic minorities; and (4) conflicting views about children’s “place” in society, especially in relation to adults. From historical, political, and advocacy perspectives, this chapter examines child rights as a concept and as lived reality for American children. The chapter concludes with speculations about the potential for making child rights a higher priority in the US and, perhaps, someday joining the world community by ratifying the UNCRC.
Effective Innovation Management in Strategic Planning

When designing how to structure an organization, administrative staff take into account a variety of things. Of these, the most ubiquitous challenge for management is typically how to ensure that the different departments within an overarching organization can operate together efficiently. This is exactly the goal of innovative management and strategic planning. By implementing a variety of techniques, companies can ensure that the goals of the different departments and employees align to a common objective. This process also can aid organizational management to establish the best and most efficient use of resources. By implementing innovation management in strategy planning information technology-based companies can fortify the strengths of the different departments and facilitate the overall success of the organization.
Genomic and experimental evidence that alternate transcription initiation of the Anaplastic Lymphoma Kinase (ALK) kinase domain does not predict single agent sensitivity to ALK inhibitors

Genomic data can facilitate personalized treatment decisions by enabling therapeutic hypotheses in individual patients. Conditional selection, which includes mutual exclusivity, is a signal that has been empirically useful for identifying mutations that may be sensitive to single agent targeted therapies. However, a low mutation frequency can underpower this signal for rare variants and prevent robust conclusions from genomic data. We develop a resampling based method for the direct pairwise comparison of conditional selection between sets of gene pairs. This effectively creates positive control guideposts of mutual exclusivity in known driver genes that normalizes differences in mutation abundance. We applied this method to a transcript variant of anaplastic lymphoma kinase (ALK) in melanoma, termed ALKATI, which has been the subject of a recent controversy in the literature. We reproduced some of the original cell transformation experiments, performed rescue experiments, and analyzed drug response data to revisit the original ALKATI findings. We found that ALKATI is not as mutually exclusive with BRAF or NRAS as BRAF and NRAS genes are with each other. We performed in vitro transformation assays and rescue assays that suggested that alternative transcript initiation in ALK is not likely to be sufficient for cellular transformation or growth and it does not predict single agent therapeutic dependency. Our work strongly disfavors the role of ALKATI as a targetable oncogenic driver that might be sensitive to single agent ALK treatment. The progress of other experimental agents in late-stage melanoma and our experimental and computational re-analysis led us to conclude that further single agent testing of ALK inhibitors in patients with ALKATI should be limited to cases where no other treatment hypotheses can be identified.
All-loop-orders relation between Regge limits of $$ \mathcal{N} $$ = 4 SYM and $$ \mathcal{N} $$ = 8 supergravity four-point amplitudes

We examine in detail the structure of the Regge limit of the (nonplanar) $$ \mathcal{N} $$ = 4 SYM four-point amplitude. We begin by developing a basis of color factors Cik suitable for the Regge limit of the amplitude at any loop order, and then calculate explicitly the coefficients of the amplitude in that basis through three-loop order using the Regge limit of the full amplitude previously calculated by Henn and Mistlberger. We compute these coefficients exactly at one loop, through $$ \mathcal{O}\left({\upepsilon}^2\right) $$ at two loops, and through $$ \mathcal{O}\left({\upepsilon}^0\right) $$ at three loops, verifying that the IR-divergent pieces are consistent with (the Regge limit of) the expected infrared divergence structure, including a contribution from the three-loop correction to the dipole formula. We also verify consistency with the IR-finite NLL and NNLL predictions of Caron-Huot et al. Finally we use these results to motivate the conjecture of an all-orders relation between one of the coefficients and the Regge limit of the $$ \mathcal{N} $$ = 8 supergravity four-point amplitude.
Social Return on Investment (SROI) to Assess the Impacts of Tourism: A Case Study:

This article contributes to the debate on the social and economic impacts generated by tourism activities using a methodology that is still insufficiently explored in the field of tourism and the i...
Adaptive Reward for CAV Action Planning using Monte Carlo Tree Search

Cooperative action planning for Connected and Autonomous Vehicles (CAVs) in an emergency scenario is an important task in the autonomous driving domain. Reinforcement learning algorithms such as Monte Carlo Tree Search (MCTS) have popularly been used to solve this problem with some success. MCTS rely on performing many simulations of CAV actions to learn expected reward values for CAV actions. A refined reward function design is a necessary precondition for better success rates in MCTS. Traditionally, predefined reward functions with fixed reward parameters are used in all CAVs scenarios by most MCTS-based algorithms. This paper presents a novel Monte Carlo Tree Search (MCTS) based algorithm that dynamically modifies the reward function parameters to encourage or discourage particular CAV actions. Our proposed algorithm with a dynamic reward function significantly improves the reliability of MCTS having a fixed reward function. We evaluate the proposed algorithm in a large-scale multi-agent-based traffic simulation system. Experimental results show that our algorithm significantly improves upon current state-of-the-art centralized and decentralized algorithms.
Proceedings before Courts of First Instance

This chapter describes ordinary proceedings before the courts of first instance. A discussion of proceedings before the tribunal de grande instance (7.01–7.15) is followed by brief descriptions of proceedings before the tribunal d’instance (7.16) and before various specialized courts (7.17–7.21). The chapter concludes with a detailed treatment of proof proceedings and rules of evidence (7.22–7.58) and a summary of the 1965 reforms (7.59–7.62).
A Profession Without Limits: The Changing Role of Reference Librarians

Reference librarians, specifically those working in academic health sciences environments, have expanded their roles and taken on new and unique responsibilities. While librarians at The George Washington University's Himmelfarb Health Sciences Library continue to provide traditional reference services, they have gone beyond their comfort zone in many cases to become involved in activities that are outside of the librarian's established role. This article describes the current roles of Himmelfarb's reference librarians, as well as the way these librarians prepared for these roles and addressed the associated challenges.
Budding in the Dimorphic Fungus Phialophora dermatitidis

Ultrastructural comparisons of yeast and hyphal bud formation in Phialophora dermatitidis reveal that bud initiation is characterized by a blastic rupture of the outer portion of the yeast or hyphal wall and the emergence of a bud protuberance through the resulting opening. The wall of the emerging bud is continuous, with only an inner wall layer of the parental yeast or hypha. The outer, ruptured portion of the parental wall typically forms a collar around the constricted emergence region of the developing bud. The cytoplasm within the very young emerging bud invariably contains a small number of membrane-bound vesicles. The septum formed between the daughter bud and the parental yeast or hypha is a complete septum devoid of a septal pore, septal pore plug, or any associated Woronin bodies characteristic of simple septa of the moniliform or true hyphae. These observations suggest that yeast bud formation and lateral hyphal bud formation in the dimorphic fungus P. dermatitidis involve a growth process which occurs identically in both the yeast and mold phase of this human pathogenic organism. Images
Integrin laminin receptors and breast carcinoma progression.

This review explores the mechanistic basis of breast carcinoma progression by focusing on the contribution of integrins. Integrins are essential for progression not only for their ability to mediate physical interactions with extracellular matrices but also for their ability to regulate signaling pathways that control actin dynamics and cell movement, as well as for growth and survival. Our comments center on the α6 integrins (α6β1 and α6β4), which are receptors for the laminin family of basement membrane components. Numerous studies have implicated these integrins in breast cancer progression and have provided a rationale for studying the mechanistic basis of their contribution to aggressive disease. Recent work by our group and others on mechanisms of breast carcinoma invasion and survival that are influenced by the α6 integrins are discussed.
ICE ON THE FAST TRACK

Could the West Antarctic Ice Sheet collapse, causing a disastrous global rise in sea level? To answer that, we must first understand the fast-flowing ice streams that stud its perimeter, carrying its ice to the sea. What controls their locations? Seismology and satellite observations give one possible answer: ice streams exist only over sedimentary basins, which supply material for a slippery clay-like bed.
Nebulin as an actin zipper. A two-module nebulin fragment promotes actin nucleation and stabilizes actin filaments

Nebulin is a family of giant muscle proteins (700-900 kDa) that interact with actin to form composite thin filaments in the skeletal muscle sarcomere. This modular protein is composed predominantly of repeating sequence modules of 31-38 residues. To understand the minimum size and number of sequence modules that are required for actin interaction, we studied the behavior of a highly soluble two-module nebulin fragment ND8 that was expressed in Escherichia coli. By fluorescence spectroscopy with pyrenyl-actin and co-sedimentation assays, we observed the following. 1) ND8 greatly accelerated actin nucleation, especially in a buffer that is suboptimal for actin nucleation. The presence of ND8 abolished the lag phase of actin polymerization and increased the net extent of steady state polymerization, thereby reducing the critical concentration of actin polymerization. 2) ND8 reduced the rate of actin depolymerization and might increase the rate of elongation. 3) Cytochalasin E, which caps both ends of actin filaments, inhibited the effect of ND8 on actin polymerization and caused the depolymerization of actin-ND8 complexes. These data suggest that ND8 interacts with actin in such a fashion that it stabilizes the actin nuclei and slows the depolymerization from the ends of actin filaments. 4) The binding stoichiometry of ND8 to F-actin, as estimated by co-sedimentation assays, is 1 to 2 mol of ND8 to 1 mol of actin with an apparent dissociation constant of 20 to 40 microM. Our data suggest that nebulin-actin interaction promotes actin nucleation and stabilizes preformed actin filaments, both of which are desirable attributes of a length-regulating template for actin filaments of the skeletal muscle. Each nebulin molecule may contain as many as 100-200 actin binding domains to form a zipper-like nebulin/actin composite filament.
Selectivity and response characteristics of human olfactory neurons

Rawson, N. E., G. Gomez, B. Cowart, J. G. Brand, L. D. Lowry, E. A. Pribitkin, and D. Restrepo. Selectivity and response characteristics of human olfactory neurons. J. Neurophysiol. 77: 1606–1613, ...
Alternative mRNA splicing of G protein-coupled receptors.

Alternative mRNA splicing as an important mechanism for generating protein diversity has been implicated to affect 60–70% of human genes (Wang et al., 2008). The G protein-coupled receptors (GPCRs), the largest group of membrane receptors, have a broad distribution and function. Posttranslational modifications or/and association with regulatory proteins can govern cell- and tissue-specific pharmacological, signaling, and regulatory characteristics of GPCRs. However, increasing body of evidence suggests that alternative splicing of GPCRs is a mechanism that can modulate GPCRs’ function (Einstein et al., 2008). Many GPCRs have a potential to undergo alternative pre-mRNA splicing (∼ 50%). Due to a general lack of isoform-specific antibodies, GPCRs’ alternative splicing is mainly studied on mRNA level employing various PCR techniques. Functional characteristics (including signaling and structure) of alternatively spliced GPCRs are studied in overexpression system employing standard biochemical techniques. In this chapter, we will describe the methods for detection and quantification of alternatively spliced GPCR mRNA. As the experimental paradigm, we use type 1 corticotropin-releasing hormone receptor (CRH-R1).
Leadership in Hospitality Education: Why Are There So Few Women?

There are few women in the higher levels of hospitality educational administration. This raises larger questions of whether women are attaining the highest levels of pay and prestige in the field. Results of a survey of those in the field show that male and female hospitality educators are paid significantly different salaries, but that the traditional areas of faculty performance (teaching, research, and service) are not performed at significantly different levels. Results indicate that possible discriminatory patterns against women in leadership positions exist or that additional factors not included in this study are responsible.
Young adults’ social skills are independent of their parents’ social skills

It has been suggested that young people's social skills are influenced by the parenting styles, and modeling of social skills by their parents. To test these hypotheses, 141 university students completed measures of social skills and engaged in a brief interpersonal interaction from which several behaviors indicative as social skills were assessed. In addition, 127 mothers and 111 fathers of these subjects completed measures of their own social skills and parenting styles. The results indicated that both parental parenting styles and parental social skills were poor predictors of the young adults’ social skills. In most cases parental predictors explained less than 10% of the variance of any of 15 social skills variables assessed in their children.
Studies of the dynamic properties of Langmuir probes I: Measuring methods☆

Abstract Three different measuring techniques are presented for use in the study of the transient behavior of Langmuir probes, immersed in a gaseous plasma. These techniques make it possible to study the dynamic behavior of positive and negative space-charge sheaths. A special type of Langmuir probe required for these studies was developed and the precautions which have to be taken with respect to the various components of the measuring circuit are discussed. Plasma phenomena observed when suddenly changing the potential of the probe with respect to the plasma are described.
Silicon Wire Waveguide Label-free Biosensor Arrays

We report silicon wire evanescent field biosensor arrays, addressed using WDM and broadcasting approaches. Simultaneous and real-time monitoring of different antibody-antigen reactions can resolved an adsorption of 0.25 pg/mm2. The two addressing approaches are compared.
The Effect of Protein Structure on their Controlled Release from an Injectable Peptide Hydrogel

Hydrogel materials are promising vehicles for the delivery of protein therapeutics. Proteins can impart physical interactions, both steric and electrostatic in nature, that influence their release from a given gel network. Here, model proteins of varying hydrodynamic diameter and charge are directly encapsulated and their release studied from electropositive fibrillar hydrogels prepared from the self-assembling peptide, MAX8. Hydrogelation of MAX8 can be triggered in the presence of proteins for their direct encapsulation with neither effect on protein structure nor the hydrogel's mechanical properties. Bulk release of the encapsulated proteins from the hydrogels was assessed for a month time period at 37 °C before and after syringe delivery of the loaded gels to determine the influence of the protein structure on release. Release of positively charged and neutral proteins was largely governed by the sterics imposed by the network. Conversely, negatively charged proteins interacted strongly with the positively charged fibrillar network, greatly restricting their release to <10% of the initial protein load. Partition and retention studies indicated that electrostatic interactions dictate the amount of protein available for release. Importantly, when protein encapsulated gels were delivered via syringe, the release profiles of the macromolecules show the similar trends as those observed for non-sheared gels. This study demonstrates that proteins can be directly encapsulated in self assembled MAX8 hydrogels, which can then be syringe delivered to a site where subsequent release is controlled by protein structure.
Abstract 2783: Inhibition of prosurvival autophagy by the BH3-mimetic obatoclax sensitizes antiestrogen-resistant breast cancer cells to apoptosis

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Antiestrogens (AEs) have long been a standard treatment for estrogen receptor-positive (ER+) breast cancer patients. However, antiestrogen resistance, either de novo or acquired, is a major hurdle for effective therapy in breast cancer patients. To address this, the underlying mechanisms of antiestrogen resistance must be understood. One common mechanism by which AE resistant cells thrive is by overexpressing BCL2 and its antiapoptotic family members, which allows cancer cells to survive under conditions that would normally cause apoptosis. We discovered that the BH3-mimetic, obatoclax (GX15-070), significantly reduces cell proliferation and, in combination with fulvestrant or tamoxifen, results in a synergistic inhibition of cell growth in AE resistant breast cancer cells. Obatoclax exhibits potency against BCL2, BCL-XL, BCLW, MCL1, and A1 and is currently being used in clinical trials directed at lymhomas and leukemia. However, the molecular mechanisms of cell death by obatoclax are unclear. We show that obatoclax induces apoptosis and autophagosome formation in AE-resistant breast cancer cells. To compensate for the increase in autophagosomal formation as measured by LC3, obatoclax also induces lysosome formation to prepare for cellular breakdown. This study is the first to show that obatoclax inhibits prosurvival autophagy by preventing the degradation of LC3 and p62 through a cathepsin-dependent mechanism. Furthermore, overexpression of BCL2 in breast cancer cells “primes” the cells with BH3-only proteins and renders the cancer cell sensitive to treatment with obatoclax. Collectively, these data support exploration of clinical trials combining an AE and the BCL2 inhibitor, obatoclax, for the treatment of AE-resistant breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2783. doi:1538-7445.AM2012-2783
Interrelationship of inflammation and tooth mobility (trauma) in pathogenesis of periodontal disease

A series of studies has investigated interactions between periodontal trauma and marginal periodontitis in relation to the initiation, progression and treatment of periodontal disease. Lesions of trauma in the periodontal ligament consequent to either single or jiggling displacing forces result in morphologic alterations in the ligament and alveolar bone. These changes do not initiate the loss of connective tissue attachment characteristic of marginal periodontitis. Studies conducted in squirrel monkeys and beagle dogs in which jiggling forces have been produced subjacent to an established marginal periodontitis reported increased loss of alveolar bone, but the accelerated loss of attachment which occurred in the dog model did not occur in the monkey model. To clarify the relative importance of inflammation and tooth mobility in the treatment of advanced periodontal disease, periodontal response was evaluated after removing traumatic and/or inflammatory components. Elimination of trauma in the presence of existing marginal inflammation did not reduce tooth mobility or increase bone volume. Osseous regeneration and decreased tooth mobility occurred after resolving both components, however, similar findings occurred after resolving inflammation in the presence of continued tooth mobility. Resolution of marginal inflammation is of prime importance in the management of periodontal disease. After resolution of inflammation, bone regeneration may occur around mobile teeth and, furthermore, any residual tooth mobility does not result in increased loss of connective tissue attachment.
Minimally invasive precision brain access using prospective stereotaxy and a trajectory guide.

Purpose To evaluate the capabilities of MR-guided “prospective stereotaxy” methods for accessing brain structures for biopsy or electrode implantation. Materials and Methods MR-guided biopsy and deep brain stimulator (DBS) electrode implantations were performed with a trajectory guide and real-time MR guidance. Imaging methods were used to plan the selected path through the brain, appropriately orient the trajectory guide, and monitor the device insertion to assure technical success and screen for hemorrhage. Assessments of technical success rate, targeting accuracy, and complications associated with this technique were performed. Results A total of 187 biopsy procedures were performed with guidance via prospective stereotaxy methods. All brain biopsies were diagnostic and two patients sustained superficial wound infections that were treated successfully with antibiotics. One patient died postoperatively of a myocardial infarction despite preoperative medical clearance. A total of 42 DBS electrode insertions were performed in patients with Parkinson's disease or dystonia. The difference between planned and actual electrode position averaged 1.2 mm ± 0.7 mm on the first pass and only a single brain penetration was required in 90% of electrode insertions. Complications included a single asymptomatic hemorrhage and two early infections, with the latter addressed by an adjustment to sterile practice. Conclusion Prospective stereotaxy, in combination with a trajectory guide, has been proven capable of efficiently and accurately targeting structures throughout the brain. J. Magn. Reson. Imaging 2008;27:737–743. © 2008 Wiley-Liss, Inc.
Culturally Competent Practice with African American Juvenile Sex Offenders

African American juveniles adjudicated for sexual offenses may struggle with the mistrust of both the judicial and treatment systems. Unlike general mental health services, juvenile sex offender treatment is often mandated by the court or child welfare services, thus these youths and their families must engage in the treatment process. Without clinicians and services that can acknowledge and respond to a minority youth’s experience in a sensitive, culturally competent manner, there could be significant resistance to treatment. Traditional treatment approaches fail to prioritize issues involving cultural competence. This article addresses the unique challenges of African American juvenile sex offenders and makes recommendations for creating culturally competent practice for these youth and their families.
Epistemic issues in the free will debate: can we know when we are free?

In this paper, I argue that the views of Robert Kane on the one hand and John Fischer and Mark Ravizza on the other both lead to the following conclusion: we should have very low confidence in our ability to judge that someone is acting freely or in a way for which they can be held responsible. This in turn means, I claim, that these views, in practice, collapse into a sort of hard incompatibilist position, or the position of a free will denier. That would at least be an unintended consequence, and it might be regarded as a virtual reductio. Versions of the objection could likely be made against a number of other accounts of free will, but I will limit my focus to Kane and Fischer. Along the way, by way of response to some possible objections to my argument, I make some comments about epistemic closure principles.
An Fe-Ni Bubble in the Small Magellanic Cloud Supernova Remnant B0049-73.6

We present observations with the Chandra X-Ray Observatory of the supernova remnant (SNR) B0049-73.6 in the Small Magellanic Cloud (SMC). The remnant shows outer emission from swept-up SMC gas and a bright ejecta-dominated ring in the interior. The X-ray spectrum of the outer shell shows normal SMC abundances and allows us to estimate the current blast wave speed at 570 km s-1 from Sedov models. The swept-up mass is equal to 170 M⊙, the SNR age is 14,000 yr, and the explosion energy is 8.1 × 1050 ergs. The brightest parts of the inner ring are dominated by O- and Ne-rich heavy-element ejecta. B0049-73.6 is thus a remnant of a core-collapse explosion. More diffuse interior ejecta emission shows less prominent O and Ne lines. The total mass of O within the heavy-element ejecta is about 0.3 M⊙. The filling fraction of the O-rich gas is less than 1%, and its average ionization timescale of 5 × 1010 cm-3 s suggests that the observed emission is dominated by relatively dense (ne ~ 0.2 cm-3) ejecta. The bright inner ring most likely is composed of the innermost ejecta swept up by a central "nickel bubble" resulting from radioactive energy input from freshly synthesized 56Ni. This is in a qualitative agreement with theoretical predictions of such centrally located Fe-Ni bubbles, and it confirms the important role of the Ni bubble effect in determining the innermost ejecta structure in core-collapse supernovae.
Potential impact of sea level rise on coastal surges in southeast Louisiana

Abstract Potential impacts of 0.5 and 1.0 m of relative sea level rise (RSLR) on hurricane surge and waves in southeast Louisiana are investigated using the numerical storm surge model ADCIRC and the nearshore spectral wave model STWAVE. The models were applied for six hypothetic hurricanes that produce approximately 100 yr water levels in southeastern Louisiana. In areas of maximum surge, the impact of RSLR on surge was generally linear (equal to the RSLR). In wetland or wetland-fronted areas of moderate peak surges (2–3 m), the surge levels were increased by as much as 1–3 m (in addition to the RSLR). The surge increase is as much as double and triple the RSLR over broad areas and as much as five times the RSLR in isolated areas. Waves increase significantly in shallow areas due to the combined increases in water depth due to RSLR and surge increases. Maximum increases in wave height for the modeled storms were 1–1.5 m. Surge propagation over broad, shallow, wetland areas is highly sensitive to RSLR. Wave heights also generally increased for all RSLR cases. These increases were significant (0.5–1.5 m for 1 m RSLR), but less dramatic than the surge increases.
Criteria for establishing the adequacy of a sentinel lymphadenectomy.

Abstract Background Criteria are needed that could be used to terminate a sentinel lymphadenectomy for breast cancer prior to removing every sentinel lymph node, without increasing false negative rates. Methods Quantitative information on the radioactivity and color of sentinel lymph nodes removed from 541 breast cancer patients was correlated with pathologic information to determine when a sentinel lymphadenectomy could be terminated based on characteristics of the initially removed nodes. Results Tumor was found in the first two sentinel lymph nodes removed in 127 of 129 node-positive patients. In 65% of patients who were able to be evaluated, the most radioactive lymph node was a positive lymph node. When any axillary lymph node was blue, then the first tumor-containing sentinel lymph node was also blue. Conclusions Removal of the most radioactive lymph node does not insure accurate assessment of the axilla. Removal of two sentinel lymph nodes accurately staged 98.4% of node-positive patients and 99.6% of the entire study population.
INTEROCULAR TRANSFER OF DISCRIMINATIONS IN THE PIGEON1

Pigeons with one eye covered were trained to discriminate intensities or colors of stimuli located to one side of the head, or intensities, colors or forms of stimuli located in front of the beak. Each discrimination transferred to the covered eye, even when previous training with the covered eye included the reversal of the tested discrimination. Pigeons also were able to learn conditional discriminations in which appropriate responding depended on which eye was covered.
Direct evidence that the proton motive force inhibits membrane translocation of positively charged residues within membrane proteins.

The M13 phage procoat protein requires both its signal sequence and its membrane anchor sequence in the mature part of the protein for membrane insertion. Translocation of its short acidic periplasmic loop is stimulated by the proton motive force (pmf) and does not require the Sec components. We now find that the pmf becomes increasingly important for the translocation of negatively charged residues within procoat when the hydrophobicity of the signal or membrane anchor is incrementally reduced. In contrast, we find that the pmf inhibits translocation of the periplasmic loop when it contains one or two positively charged residues. This inhibitory effect of the pmf is stronger when the hydrophobicity of the inserting procoat protein is compromised. No pmf effect is observed for translocation of an uncharged periplasmic loop even when the hydrophobicity is reduced. We also show that the ΔΨ component of the pmf is necessary and sufficient for insertion of representative constructs and that the translocation effects of charged residues are primarily due to the ΔΨ component of the pmf and not the pH component.
Fragile Estuarine SYSTEMS?ECOLOGICAL Considerations

Studies of fish species and populations indicate a high degree of fragility for estuarine ecosystems. Slight stresses tend to disrupt energy flow systems and lead to lower levels of biological productivity, shortened food chains and poorer diversity of species. For individual species low-level stresses tend to suppress metabolism and growth processes. Minor stresses can also substantially reduce populations. Stress processes are quantifiable and amenable to mathematical modeling.
A Primary Role for K+ and Na+ Efflux in the Activation of Apoptosis

Cell shrinkage is a major characteristic of apoptosis, but the mechanism and role of this process in cell death are poorly understood. The primary factor that controls volume regulation in all cells is ions, and thus we have examined the movement of ions at the single cell level in lymphocytes during apoptosis. Activation of the death program with several stimuli that act through independent pathways to stimulate apoptosis results in a synchronous shift of cells from a normal cell size to a shrunken cell size. Only the shrunken cells exhibit DNA fragmentation and an approximate 4-fold elevation of caspase-3-like activity. Analysis of K+ and Na+ ion content of individual cells by flow cytometry revealed that the intracellular ionic strength of apoptotic cells decreased substantially from their non-shrunken counterparts. Additionally, we show apoptosis is enhanced under conditions where the intracellular K+ concentration is diminished and that apoptosis is inhibited when K+ efflux is prevented. These data show that the efflux of ions, primarily potassium, plays a necessary and perhaps a pivotal role in the cell death program.
Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation.

The mechanism of intercalation and the ability of double stranded DNA (dsDNA) to accommodate a variety of ligands in this manner has been well studied. Proposed mechanistic steps along this pathway for the classical intercalator ethidium have been discussed in the literature. Some previous studies indicate that the creation of an intercalation site may occur spontaneously, with the energy for this interaction arising either from solvent collisions or soliton propagation along the helical axis. A subsequent 1D diffusional search by the ligand along the helical axis of the DNA will allow the ligand entry to this intercalation site from its external, electrostatically stabilized position. Other mechanistic studies show that ethidium cation participates in the creation of the site, as a ligand interacting closely with the external surface of the DNA can cause unfavorable steric interactions depending on the ligands' orientation, which are relaxed during the creation of an intercalation site. Briefly, such a site is created by the lengthening of the DNA molecule via bond rotation between the sugars and phosphates along the DNA backbone, causing an unwinding of the dsDNA itself and separation between the adjacent base pairs local to the position of the ligand, which becomes the intercalation site. Previous experimental measurements of this interaction measure the enthalpic cost of this part of the mechanism to be about −8 kcal/mol. This paper reports the observation, during a computational study, of the spontaneous opening of an intercalation site in response to the presence of a single ethidium cation molecule in an externally bound configuration. The concerted motions between this ligand and the host, a dsDNA decamer, are clear. The dsDNA decamer AGGATGCCTG was studied; the central …GATG… site was the intercalation site.
OPPORTUNISTIC FOREIGN POLICY AND THE POLITICAL MANAGEMENT OF THE NEWS MEDIA CONTENT: THE CASE OF GRENADA

This paper presents an example of foreign policy decision making motivated primarily by opportunistic desires to make gains in domestic politics through foreign policies. An opportunistic action is similar to the international conflicts studied in the diversionary theories of war, where leaders act conflictually in international conflict in response to domestic conflict. However, an opportunity decision is broader in that it has the capability of addressing instances where the leader is simply pursuing gains rather than responding to domestic unrest, and more specific in that it focuses on the media s influence on policy and the president's efforts to manage the content of the news. An opportunistic foreign policy action is when the president acts dramatically to use the near zero-sum nature of the domestic news media to distract from a troublesome issue that the leader either cannot, or does not wish to address directly. To highlight the model, the US invasion of Grenada is examined briefly as an exemplary case.