cssi/SciSciGPT-SciSciNet huggingface dataset:
Peripheral education of the immune system by colonic commensal microbiota

Understanding how the immune system becomes tolerant to foreign antigens from commensal bacteria is a fundamental question, as breakdown of tolerance can result in unwanted responses such as inflammatory bowel disease. It has been suggested that tolerogenic regulatory T (Treg) cells are generated in response to commensal bacteria, but there is little direct evidence to support this hypothesis. A study of the colonic T-cell antigen receptor repertoire of mice now shows that microbial antigens direct the generation of antigen-specific inducible Treg cells in the colon. Commensal-induced Treg cells seem to maintain mucosal tolerance and protect mice from colitis. The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3+ regulatory T (Treg) cells1. However, it is unknown whether T cells are also educated to be tolerant of foreign antigens, such as those from commensal bacteria, to prevent immunopathology such as inflammatory bowel disease2,3,4. Here we show that encounter with commensal microbiota results in the peripheral generation of Treg cells rather than pathogenic effectors. We observed that colonic Treg cells used T-cell antigen receptors (TCRs) different from those used by Treg cells in other locations, implying an important role for local antigens in shaping the colonic Treg-cell population. Many of the local antigens seemed to be derived from commensal bacteria, on the basis of the in vitro reactivity of common colon Treg TCRs. These TCRs did not facilitate thymic Treg-cell development, implying that many colonic Treg cells arise instead by means of antigen-driven peripheral Treg-cell development. Further analysis of two of these TCRs by the creation of retroviral bone marrow chimaeras and a TCR transgenic line revealed that microbiota indigenous to our mouse colony was required for the generation of colonic Treg cells from otherwise naive T cells. If T cells expressing these TCRs fail to undergo Treg-cell development and instead become effector cells, they have the potential to induce colitis, as evidenced by adoptive transfer studies. These results suggest that the efficient peripheral generation of antigen-specific populations of Treg cells in response to an individual’s microbiota provides important post-thymic education of the immune system to foreign antigens, thereby providing tolerance to commensal microbiota.
Single Cell Isolation of Bacteria from Microbial Fuel Cells and Potomac River Sediment

Electrochemically active bacteria (EAB) are prominently found in aquatic environmental sediment samples and wastewater streams, which are known to contain several different types of microorganisms. Even though microbial consortia are found to enhance both Coulombic efficiency and total power output in microbial fuel cells (MFCs), it is currently unknown how many different EAB contribute to current generation in these systems. It is also difficult to track the relative population of different species during MFC operation. We used biological laser printing (BioLP) to isolate different bacterium from complex environmental samples and MFC anolytes. BioLP can be used to print droplets containing a single cell directly from liquid culture, thereby enabling EAB to be sorted from unmodified environmental or MFC samples. Isolated species were identified through 16S rDNA analysis of pure cultures derived from the printed samples. These experiments demonstrate how cell printing can be used as a single-step method to separate and identify microorganisms from complex environmental samples and operating MFCs.
Prognostic profile for patients with pheochromocytoma derived from clinical and pathological factors and DNA ploidy pattern.

Eighty-eight patients with pheochromocytoma and paraganglioma treated over a 28 year period (1960–1987) were studied. Based on clinical course, they were divided into three prognostic groups: benign (n = 57); multiple (n = 12); and metastatic (n = 19). Using clinical data, histopathologic findings, and tumor nuclear DNA content a prognostic profile for each group was constructed. The following variables were studied: age, familial pheochromocytoma, associated endocrine or neoplastic disorders, number and location of the lesion at diagnosis, size of the tumor, and the nuclear DNA ploidy pattern. Of these prognostic factors the most significant to predict a future malignant clinical course were large size and local tumor extension at time of surgery. Family history of pheochromocytoma, associated endocrine disorders, and young age at presentation predicted multiplicity. Old age, absence of familial pheochromocytoma or related endocrine disorders and DNA diploid tumors seem to be favorable findings. Using these variables in combination may be helpful for early identification of patients with malignant, multiple, or benign pheochromocytoma and paraganglioma. © 1992 Wiley-Liss, Inc.
Recursive and trellis-based feedback reduction for MIMO-OFDM with transmit beamforming

We consider a MIMO-OFDM system with transmit beamforming applied on each OFDM subcarrier, where each beamforming vector is drawn from a codebook with finite size. Depending on the channel realization, the receiver decides the optimal beamforming vector on each subcarrier, and informs the transmitter through a rate-limited feedback link. Exploiting the fact that the channel responses across OFDM subcarriers are correlated, we propose two methods to reduce the amount of needed feedback. One is recursive feedback encoding that selects the optimal beamforming vectors sequentially across the subcarriers, and adopts a smaller-size time-varying codebook per subcarrier depending on prior decisions. The other is trellis-based feedback encoding that selects the optimal beamforming vectors for all subcarriers at once along a trellis structure via the A. The trellis-based feedback encoding outperforms the recursive feedback encoding at the expense of encoding complexity at the receiver. Simulation results demonstrate that our trellis-based approach outperforms an existing interpolation-based alternative, as the latter incurs diversity loss at high SNR
Proton Irradiation Effect on CdSe-ZnS Core-Shell Nanocrystals Embedded in Ultra Violet Curable Resin

This work focuses on investigating the effect of proton irradiation on the optical properties of CdSe-ZnS core-shell nanocrystals embedded in ultra-violet curable resin. The excitonic transitions were measured using optical absorbance and photoluminescence (PL) techniques. Nanocrystals of three different diameters, 4.5nm, 2.7nm and 2.1nm were used which showed the first exciton peak at wavelengths 600nm, 552nm and 498nm respectively. These samples were subjected to 2MeV protons at different fluence levels. The optical absorbance spectra were collected after the exposure to protons. The integrated area of excitonic transition was monitored as a function of proton fluence. The results indicate that for 4.5nm nanocrystals, the proton irradiation doses up to 9.03 x 1015 protons-cm-2 had little effect on the excitonic transitions. However radiation-related degradation seemed to increase with the decreasing size of nanocrystals. No excitonic transition was observed in 2.1 nm nanocrystals from the fluence of 6 x 1015 protons-cm-2. This seems to be due to the probable degradation in the resin with the increasing proton fluence. Photoluminescence (PL) measurements were also conducted on 4.5nm nanocrystals using Bomem FT spectrometer. The excitonic transitions were measured at 300K and 77K and small degradation has been observed as understood from the decreasing integrated area with the increasing proton fluence.
Reading Neoplatonism: Non-discursive Thinking in the Texts of Plotinus, Proclus, and Damascius

Preface: discursive strategies and Neoplatonic texts Acknowledgements List of abbreviations 1. Introduction. Representing a tradition: exegesis, symbol and self-reflection Part I. Language in the Enneads: 2. Plotinus' critique of discursive thinking 3. Non-discursive thinking in the Enneads 4. Introspection in the dialectic of the Enneads 5. The symbolism of the Enneads Part II. Text and Tradition in Neoplatonism: 6. History of an enigma: mathematical symbolism in the Neoplatonic tradition 7. Transmigrations of a myth: Orphic texts and Platonic contexts 8. Language and theurgy in Proclus' Platonic Theology 9. Damascius' ineffable discourse 10. Conclusion: reading Neoplatonism References General index Index locorum.
Mechanisms for species-selective oriented crystal growth at organic templates

Langmuir monolayers floating on supersaturated aqueous subphases can act as templates for the growth of oriented inorganic films—a “bioinspired” nucleation process. We have performed in situ grazing incidence x-ray diffraction studies of the selective nucleation of BaClF and BaF2 under fatty acid monolayers. The arrangement of the fatty acid headgroups, the monolayer charge, and ion-specific effects all play important roles in selecting the inorganic species. When the monolayer is in a neutral state, both BaClF and BaF2 nucleate at the interface and are well aligned, but when the monolayer headgroup is deprotonated, only oriented BaF2 grows at the interface. We also observe an enhanced alignment of BaF2 crystals during growth from highly supersaturated solutions, presumably due to reorganization of preformed crystals at the organic template. These results show that a delicate interplay between multiple factors governs the oriented growth of inorganic films at organic templates.
On the value of formal assessment of uncertainty in regulatory analysis

The US Office of Management and Budget introduced in 2003 a new requirement for the treatment of uncertainty in Regulatory Impact Analyses (RIAs) of proposed regulations, requiring agencies to carry out a formal quantitative uncertainty assessment regarding a regulation’s benefits and costs if either is expected to reach $1 billion annually. Despite previous use in other contexts, such formal assessments of uncertainty have rarely been employed in RIAs or other regulatory analyses. We describe how formal quantitative assessments of uncertainty – in particular, Monte Carlo analyses – can be conducted, we examine the challenges and limitations of such analyses in the context of RIAs, and we assess how the resulting information can affect the evaluation of regulations. For illustrative purposes, we compare Monte Carlo analysis with methods typically used in RIAs to evaluate uncertainty in the context of economic analyses carried out for the US Environmental Protection Agency’s Nonroad Diesel Rule, which became effective in 2004.
Two (or three) is not equal to one: Multiple jobholding as a neglected topic in organizational research

Summary The objective of this Incubator is to stimulate research in the area of multiple jobholding (MJH), a longneglected topic in organizational behavior. We first discuss the prevalence of, and motivation for, MJH and then discuss possible dangers and benefits of MJH. Throughout, we discuss ideas for future research. Copyright © 2014 John Wiley & Sons, Ltd.
Identification of research gaps from evidence-based guidelines: a pilot study in cystic fibrosis.

Objectives: Evidence-based guideline committees are multidisciplinary and explicitly consider the existing evidence. They are thus in an ideal position to identify research gaps. However, gaps have not been systematically identified through guidelines. We pilot tested a method to systematically identify and classify gaps from evidence-based guidelines. Methods: We reviewed all evidence-based guidelines published by the Cystic Fibrosis Foundation. We identified research gaps as topics for which there was insufficient evidence (recommendations were not made or consensus recommendations were made) and topics specified as needing further research. We characterized gaps using a standard framework and classified them by type of management issue, specificity of target population, and age of target population. Results: We identified sixty-two research gaps in five guidelines (mean = 12.4/guidelines document). While thirteen gaps were topics specified as needing further research, most ( n = 49) were topics with insufficient evidence. Of these forty-nine, recommendations were not made for twenty-two topics while consensus recommendations were made for twenty-seven topics. Most gaps were issues of comparative effectiveness (44/62), addressed the general cystic fibrosis population (40/62), and were specific to infants (33/62). Relevant comparisons and outcomes were explicitly stated for only 7 percent and 16 percent of gaps respectively. Conclusions: Almost 80 percent of the gaps were not topics identified as future research needs in the guidelines documents but rather were topics with insufficient evidence for making recommendations. Although we used cystic fibrosis in the United States as an example, the method we developed could be applied in other settings, including other countries and for different diseases.
Adaptive output-feedback design for a class of nonlinear discrete-time systems

We present adaptive output-feedback schemes for a class of discrete-time systems whose continuous-time counterparts are the output-feedback canonical form. We first develop a systematic design procedure for the deterministic case. Global boundedness and convergence are achieved with no restriction imposed on the nonlinearities. Then we proceed to develop an analogous design procedure for the adaptive case. Depending on the characteristics of the nonlinearities, global boundedness and convergence can be achieved with various update laws. A rank condition is required to ensure such properties for nonlinearities which are not globally Lipschitz. >
Chemotherapy-Related Cognitive Impairment: The Breast Cancer Experience

Purpose/objectives To provide an in-depth description of the experience of chemotherapy-related cognitive impairment (CRCI) for women with breast cancer and identify related information that women would find useful prior to chemotherapy and at the onset of cognitive changes. Research approach Qualitative, descriptive design. Setting Academic breast cancer survivorship center in Kansas City, KS. Participants 18 breast cancer survivors within 6-12 months of having completed chemotherapy who self-reported changes in cognitive function. Methodologic approach Data were collected with a demographic questionnaire, semistructured interviews, and a focus group. Qualitative content analysis was performed. Findings Study themes were Life With Chemobrain, How I Changed, How I Cope, and How to Teach Me. Participants described difficulty with short-term memory, focusing, word finding, reading, and driving. Issues with fatigue, trouble sleeping, neuropathy, balance, and coordination also were of concern. Coping strategies included writing things down, depending on others, focusing on one task at a time, and giving oneself permission to make mistakes. Participants described exercise and getting enough rest to be helpful and recommended activities to stimulate the mind. Participants wanted information about the potential for CRCI prior to initiating chemotherapy and desired an individualized approach to education. Specific recommendations for education were provided. Conclusions The study results provide a framework for understanding the experience of CRCI that can be used to guide development of patient and family education and generate questions for additional research. Interpretation Application of the study results will enhance informed consent, validate the experience of CRCI, and contribute to patient satisfaction.
Thrombospondin-1: An Extracellular Message Delivered by Macrophages That Promotes Aortic Aneurysms

Inflammation plays a critical role in a broad range of human diseases. The immune system must create sufficient inflammation to protect the host from infectious agents without causing hypercytokinemia and chronic inflammation that increases the risk for developing diseases ranging from autoimmunity to cancer. Many factors influence the strength and duration of inflammatory responses, including genetics, environmental factors, and the microbiome.1 Recruitment of circulating innate immune cells is a key step in initiating local inflammation, and the work of Liu et al2 in this issue provides novel insights into the role of bone marrow (BM)–derived inflammatory cells in the pathogenesis of abdominal aortic aneurysms (AAA). Article, see p 129 The pathogenesis of human AAA occurs over many years and involves decreased elastin deposition, increased vascular smooth muscle cell death, immune cell infiltration, atherosclerosis, and thrombi. In contrast, mouse models of AAA use an acute injury to generate chronic aortic inflammation, leading to aneurysm formation in the following weeks.3 The elastase and CaCl2 models induce pathologies that resemble human AAA and are the preferred models to address the role of inflammatory cells and study specific gene deletions. The angiotensin-II model is restricted to Apoe −/− mice but exhibits robust thrombus and atherosclerosis pathology that is lacking from other models. Liu et al2 identify an important role for BM-derived monocytes and thrombospondin-1 in each of these models and in human AAA tissues. The authors had several reasons to focus on the secreted matricellular protein thrombospondin-1. Thrombospondin-1 plays known roles in other diseases of large vessels, including atherosclerosis and pulmonary arterial hypertension,4 and signaling through thrombospondin-1 receptors on vascular cells controls signaling pathways that regulate vascular physiology.5 Thrombospondin-1 is also known to regulate inflammatory responses in infectious diseases, cardiovascular disease, reperfusion injuries, and cancer.6– …
Dynamic and extensive metabolic state-dependent regulation of cytokine expression and circulating levels

Cytokines play diverse and critical roles in innate and acquired immunity, and several function within the central nervous system and in peripheral tissues to modulate energy metabolism. The extent...
Experimental Investigation of a Large-Scale Composite Riser Tube Under External Pressure

A collapse pressure test was conducted on a full-scale diameter prototype composite offshore drilling riser. The test specimen was a carbon fiber-epoxy filament-wound tube, approximately 56.4 cm outside diameter and 3.05 cm wall thickness. The tube was subjected to external water pressure up to collapse. The purpose of the test was to confirm the external pressure capacity of the specimen and to provide a basis for verification and calibration of analytical estimates of the collapse pressure of large scale carbon fiber tubes. The specimen was instrumented with strain gauges on both the outside and inside walls of the tube. This paper describes the test specimen and presents key results of the test.
A Systems Approach to Post-conflict Rehabilitation

War represents the ultimate breakdown of communication, relationships, and societal systems. The purpose of this chapter is to introduce the basic concepts of systems theory, discuss how this framework transcends the separation between mental health and psychosocial trauma rehabilitation, review the pertinent research regarding collective trauma rehabilitation, and outline the recommendations and model interventions that have evolved as a result of the implementation of this meta-theoretical framework.
Global Law Firms in Real-World Contexts: Practical Limitations and Ethical Implications

This article argues that despite the rise in the numbers of global law firms in recent years, the future of these firms should not be assumed given escalating levels of economic (and legal) uncertainty. These uncertainties are the result, in part, of growing global and regional conflicts, terrorism, environmental degradation, pandemics, forced migrations, trade embargoes and so on which are in turn linked to global inequalities and disparities of wealth between and within the global south and global north. It is argued that global law firms, as the “lubricators of global capitalism”, should pay attention to the localized real-world impacts of finance, development and trade that their legal work enables. This is important not only to ensure the future security and revenues of global law firms, but more importantly to ensure democratic aspirations and the stability of democratic institutions around the world.
Temozolomide and/or Erlotinib in the Treatment of Lung Cancer Patients With Progressive Central Nervous System Metastases

Background: Patients with lung cancer who develop brain metastases have a poor prognosis. Those patients with progressive brain metastases tend to have a dismal prognosis. Currently, there is no standard of care for the treatment of these patients. Methods: In this manuscript, we present a retrospective evaluation of 10 patients treated at our institution with a combination of temozolomide and / or erlotinib after disease progression in the central nervous system following radiation therapy. Results: Median overall survival was 28 weeks. Median time to progression in the central nervous system was 14 weeks. Median time to progression systemically was 7.5 weeks. Some patients demonstrated prolonged stability of disease. Conclusions: A palliative regimen of temozolomide and / or erlotinib could be considered in progressive central nervous system metastases from lung cancer. doi:10.4021/jnr85w
Population Pharmacokinetic–Pharmacodynamic (PK/PD) Modeling of Anti-infective Agents and Its Applications to Individualized Therapy

This chapter describes the general principles of population pharmacokinetic–pharmacodynamic (PK/PD) modeling and its application to optimization of antibiotic dosing. Parametric and nonparametric pharmacokinetic modeling approaches are discussed. Population modeling will identify central tendency of PK/PD parameter estimates, quantify between and within patient variability, and identify clinically useful covariates. Population modeling has become an important component of quantitative model-based drug development. In addition, PK/PD models can be important extensions of therapeutic drug management in infectious diseases. The concept of population model-based individualized antimicrobial therapy is described. With the availability of population modeling for obtaining PK parameter estimates, the focus has shifted to quantifying the antimicrobial effect and linking kinetics to drug effects. Mathematical models that link drug exposure (PK) with PD indices that correlate with microbiological and clinical outcomes will provide us with a better rationale for proper dose selection of antimicrobial therapy in different patient populations.
Gastric secretion and motility in dogs post-vagotomy: two year studies.

Summary Two year post-vagotomy studies in dogs demonstrate that the acid secretory response remains depressed to local stimulation, and completely absent to cerebral stimulation. Gastric motility observed fluoroscopically was normal, but a high degree of pylorospasm was present in 4 of the 7 dogs, thus delaying the emptying time. Gastric motility response to insulin was negative in each case, thereby attesting to the completeness of the vagotomy.
Efficacy of Complementary and Alternative Medicine Approaches for Pediatric Pain

Pain may be a major cause of physical and emotional distress in chronic pediatric conditions, including cancer, juvenile arthritis, and cystic fibrosis. Complementary and alternative medical (CAM) therapies have become important and frequently used modalities in treating children’s pain. Yet, many practitioners have questioned whether there is sufficient evidence to support the efficacy and safety of CAM approaches for pain relief. This chapter aims to address these concerns by presenting a critical review of the available published evidence. We evaluated published studies testing CAM interventions for chronic or acute procedural pain; these study methodologies employed either controlled trials or multiple baseline studies. The evaluation criteria were developed by the American Psychological Association Division 12 Task Force on Promotion and Dissemination of Psychological Procedures to assess nonpharmacological therapies. Few of the CAM modalities qualify as empirically supported therapies under these rigorous criteria, although several met the standard for possibly efficacious or promising for pediatric pain. Our review of the published literature revealed a number of methodological flaws in existing studies. Clearly, more research on CAM therapies for children’s pain is needed.
Women of color and the war on crime: An explanation for the rise in Black female imprisonment

ABSTRACTSince 1972, U.S. female imprisonment has risen twice as fast as male imprisonment, with increased disparities between White females and women of color. Such disparities are particularly stark for drug crimes, for which Black and Latina women are increasingly imprisoned. This article examines the relationship between the war on crime and the pronounced rise in Black female imprisonment. An analysis of data covering 40 states from 1983–2008 indicates that although women are less likely than men to be incarcerated, nonviolent offenses, particularly drug crimes, are increasingly driving the growth in female imprisonment and growing the racial disparity in female imprisonment.
Characterization of Therapeutic Proteins

Therapeutic proteins are large biological molecules with complex structures and functions produced through complex manufacturing processes, which include multiple unit operations with finely tuned control parameters. The characterization of therapeutic protein products during development, manufacturing and at product release requires the development and qualification of appropriate analytical methods that measure physicochemical properties and biological activities. Analytical testing during product development forms the basis for identifying the critical quality attributes for the protein therapeutic product, establishing release and stability specifications, and developing an analytical comparability program that ensures safety and efficacy throughout the product life cycle. In this chapter we discuss analytical characterization in the context of the regulation of therapeutic proteins. We focus on polyclonal immune globulins, proteins for hemostasis, monoclonal antibodies, and other therapeutic proteins and emphasize the commonalities and also highlight differences in the application of laws, regulations, and guidance.
Retrospective Accounts of Religious Disaffiliation in the United States: Stressors, Skepticism, and Political Factors

According to two recent reports, between 15 and 18 percent of Americans are now religiously unaffiliated, up from 7 percent in 1991. Using Wave 1 of the Portraits of American Life Study (PALS), I find that 13 percent of religiously affiliated Americans seriously considered leaving religion altogether between 2003 and 2006. However, less than half went on to actually disaffiliate by 2006. This study examines four key issues associated with both considering and actually leaving religion and investigates differences between religious stayers and leavers. In particular, I examine the potential influence of political attitudes, religious skepticism, life stressors, and sociodemographic characteristics. Results of binary and multinomial logistic regression analyses reveal that each is associated with considering and leaving religion, but not necessarily in uniform and expected directions.
What Reverses Decentralization? Failed Policy Implementation, Civic Supporters, or Central Bureaucrats’ Expertise? The Case of Brazil’s AIDS Program

This article argues that Brazil’s success in responding to the AIDS epidemic rested in the government’s pursuit of a reversal of decentralization, which entailed the government’s delegation of policy-making autonomy, funding, and discretionary fiscal transfers to the national AIDS program. AIDS bureaucrats achieved this by establishing close partnerships with social health movements and AIDS nongovernmental organizations advocating policy ideas with a historically proven track record of success while resembling similar social health movements in the past. This partnership, in turn, provided AIDS bureaucrats with the legitimacy and influenced needed for policy reform.
Intercanyon movement of marked Culex tarsalis (Diptera: Culicidae).

Field-collected Culex tarsalis mosquitoes were marked and released in each of 3 adjacent canyons in California, USA, to study population exchange. Males failed to disperse from the canyon in which they were released. Females moved freely among the canyons; immigrants were more likely to have mated prior to recapture than nonmigrants. Parity rates were generally lower for females collected in shelters than for those in CO2-augmented trap collections; a high degree of autogeny may have resulted in undersampling of nullipars in traps.
A RANDOMIZED CLINICAL TRIAL COMPARING EXTENSIBLE AND INEXTENSIBLE LUMBOSACRAL ORTHOSES AND STANDARD CARE ALONE IN THE MANAGEMENT OF LOWER BACK PAIN

Study Design Single blinded, randomized clinical trial for the evaluation of lumbosacral orthoses (LSOs) in the management of lower back pain (LBP).
Fluorescence Endomicroscopy with Out-of-Focus Background Rejection

We present a novel fluorescence endomicroscope that provides out-of-focus background rejection. Our technique is based on structured and speckled laser illumination.
[(HL)2Fe6 (NCMe)m]n+ (m = 0, 2, 4, 6; N = -1, 0, 1, 2, 3, 4, 6): An electron-transfer series featuring octahedral Fe6 clusters supported by a hexaamide ligand platform

Using a trinucleating hexaamide ligand platform, the all-ferrous hexanuclear cluster (HL)2Fe6 (1) is obtained from reaction of 3 equiv of Fe2(Mes)4 (Mes = 2,4,6-Me3C6H2) with 2 equiv of the ligand (HL)H6. Compound 1 was characterized by X-ray diffraction analysis, 57Fe Mossbauer, SQUID magnetometry, mass spectrometry, and combustion analysis, providing evidence for an S = 6 ground state and delocalized electronic structure. The cyclic voltammogram of [(HL)2Fe6]n+ in acetonitrile reveals a rich redox chemistry, featuring five fully reversible redox events that span six oxidation states ([(HL)2Fe6]n+, where n = −1 → 4) within a 1.3 V potential range. Accordingly, each of these species is readily accessed chemically to provide the electron-transfer series [(HL)2Fe6(NCMe)m][PF6]n (m = 0, n = −1 (2); m = 2, n = 1 (3); m = 4, n = 2 (4); m = 6, n = 3 (5); m = 6, n = 4 (6)). Compounds 2–6 were isolated and characterized by X-ray diffraction, 57Fe Mossbauer and multinuclear NMR spectroscopy, and combustion analysi...
Special-"T" Training: Extended Follow-up Results from a Residency-Wide Professionalism Workshop on Transgender Health.

Objective Transgender people face unique challenges when accessing health care, including stigma and discrimination. Most residency programs devote little time to this marginalized population.
The Role of LTC4 in the Development of Post-Traumatic Intracranial Hypertension

A complex series of pathophysiologic events follow the initial transfer of mechanical energy in traumatic brain injury, and constitute the secondary phenomena which are responsible for the development of intracranial hypertension. Elevation of intracranial pressure is the hallmark of post-traumatic cerebrovascular dysfunction, and reflects some combination of vasomotor dysfunction and vascular permeability abnormalities which result in a net increase in the total intracranial volume. Considerable evidence exists in the literature which demonstrates that following mechanical brain injury, local and regional abnormalities in perfusion occur, characterized by either hyperemia or ischemia [1,7]. It remains unclear, however, which of these dysfunctional vascular states is responsible for the irreparable tissue damage which occurs in the first 96 hours following injury. Obviously, the goal of therapeutics aimed at preserving potentially viable brain tissue following injury is centered around optimizing oxygen and substrate delivery to the salvagable tissue and interrupting the propagation of pathophysiologic events which subject the brain to secondary ischemic injury.
Represent, Representin', Representation: The Efficacy of Hybrid Texts in the Writing Classroom

The article explores the use of hybrid linguistic texts in the writing classroom, both as articles of study and possible models of composition. Standard English linguistic supremacy prevents many students from using their full range of linguistic knowledge. The inclusion of hybrid texts in the writing classroom might help students, in particular working class and non-white students, to establish a linguistic and cultural connection between the beliefs and practices of the academy and those of their home communities. In addition to analyzing hybrid discourse from a popular urban magazine, a newspaper article, a scholarly article, and literary non-fiction, the article analyzes several student responses to hybrid literacy narratives and several student literacy autobiographies that use hybrid discourse. The article argues that students' reading and writing of hybrid texts might increase their awareness of language and eradicate the negative consequences of standard English supremacy. Among many of the hip hop generation there is a mandate to "rep- resent," which means to display one's skill and knowledge or express one's home identity in any given social situation. Some of my students "represent" in my writing classroom through dress—oversized clothing, baseball caps, doo rags, and bling—and attitude—laid back, non-committal, and unim- pressed. When my students "represent," they see themselves as embracing their identities and cultures in the midst of academia, as playas in the college game rather than the game of college playin' them. While the academy permits my students to "represent" in dress and attitude, it does not extend this courtesy to student language. In the academy, students are told, in a variety of ways, to leave their native language at the door and embrace, instead, standard English. However begrudgingly, most
The mTOR signalling cascade: paving new roads to cure neurological disease

Defining the multiple roles of the mechanistic (formerly 'mammalian') target of rapamycin (mTOR) signalling pathway in neurological diseases has been an exciting and rapidly evolving story of bench-to-bedside translational research that has spanned gene mutation discovery, functional experimental validation of mutations, pharmacological pathway manipulation, and clinical trials. Alterations in the dual contributions of mTOR - regulation of cell growth and proliferation, as well as autophagy and cell death - have been found in developmental brain malformations, epilepsy, autism and intellectual disability, hypoxic-ischaemic and traumatic brain injuries, brain tumours, and neurodegenerative disorders. mTOR integrates a variety of cues, such as growth factor levels, oxygen levels, and nutrient and energy availability, to regulate protein synthesis and cell growth. In line with the positioning of mTOR as a pivotal cell signalling node, altered mTOR activation has been associated with a group of phenotypically diverse neurological disorders. To understand how altered mTOR signalling leads to such divergent phenotypes, we need insight into the differential effects of enhanced or diminished mTOR activation, the developmental context of these changes, and the cell type affected by altered signalling. A particularly exciting feature of the tale of mTOR discovery is that pharmacological mTOR inhibitors have shown clinical benefits in some neurological disorders, such as tuberous sclerosis complex, and are being considered for clinical trials in epilepsy, autism, dementia, traumatic brain injury, and stroke.
Modifiable Areal Unit Problem

Coined by geographers during the 1970s, the modifiable areal unit problem (MAUP) is one of the most stubborn problems in spatial analysis when spatially aggregated data are used. Data tabulated for different spatial scale levels or according to different zonal systems for the same region will not provide consistent analysis results. Since spatially aggregated data are often used not just in geographical research, but also in other social science and physical science disciplines, the MAUP has broad impacts. The MAUP effects are functions of the underlying spatial distribution of the data, and their spatial relationships to the spatial scale hierarchy and zonal systems. Several general approaches have been suggested to handle the MAUP. They include simply acknowledging its presence and possibly conducting multiscale and multizonal systems analyses to show the range of possible results. The other extreme is to develop scale-independent or insensitive analytical techniques, but it has little success. One potential direction is to develop a general framework to address the underlying processes of the MAUP. Based upon this framework, specific solutions may be developed.
Imaging Adenosine Triphosphate (ATP)

Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provide valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities.
Zinc(II) and copper(II) complexes of edampda2−: octahedral, trigonal bipyramidal and in between [edampda2−=N,N′-bis-(pyridylmethyl)ethylenediamine-N,N′-diacetate]

ZnII and CuII complexes of the ligand edampda2− [N,N′-bis(pyridylmethyl)-ethylenediamine-N,N′-diacetate] have been studied in solution by 1H n.m.r. and e.p.r. spectroscopies, respectively. [ZnII(edampda)] exists in solution in a major octahedral isomer (ca. 83%) in which the two carboxylate donors and two pyridylmethyl donors remain stereochemically rigid up to 333K at pD=6.0. The major octahedral complex has equivalent glycinato and pyridyl donors as shown by equivalent AB quartets for each type of chelate. By contrast, the [ZnII(edta)]2− analogue complex is known to have processes which rapidly equilibrate the coordinated carboxylates leading to coalesced, broad singlets instead of AB quartets down to 273K (freezing point of the sample). The minor [ZnII(edampda)] species has one pendant pyridylmethyl arm. The complex does not increase in abundance up to 333K via dissociation of the major species, suggesting that it possesses a different five-coordinate geometry (approximate trigonal bipyramid). The [CuII(edampda)] complex exhibits an e.p.r. spectrum that is intermediate between rhombic or tetragonal CuII complexes (near D4h) and the “reversed-e.p.r.” type of trigonal bipyramidal CuII complexes (ca. D3h). The single g value of 2.079 for g∥≅g⊥>2.03 identifies the [CuII(edampda)] complex as distorted toward trigonal bipyramidal whereas its [CuII(edtaH2)(H2O)] analogue is known to be distorted toward square pyramidal. A binuclear CuI complex of edampda2− is formed only as a transient, and it rapidly disproportionates into [CuII(edampda)] and Cu metal. A mononuclear [CuI(edampda)]− complex persists for up to 8 h, but is oxidized within 3 min by O2 to the CuII complex. [CuII(edampda)] oxidizes to CuIII with a highly irreversible wave on glassy-carbon at +1.09V compared to the [NiII/III(edampda)] wave at +1.32V.
Epithelioid Hemangioendothelioma Presenting as Inferior Vena Cava Obstruction Diagnosed Using an Endovascular Thrombectomy Device

Epithelioid hemangioendothelioma is a rare vascular sarcoma that arises from the lining (intima) of blood vessels. We report a case of a 43-year-old male patient, who presented with inferior vena cava (IVC) obstruction and acute bilateral lower extremity deep vein thrombosis. Mechanical thrombectomy was performed with an endovascular thrombectomy device, followed by stent placement in the IVC. The initial pathology on the retrieved specimen obtained from the thrombectomy device revealed an undifferentiated neoplasm, and definitive surgical resection of the retroperitoneal soft-tissue tumor of the IVC documented a rare case of epithelioid hemangioendothelioma.
Hepatocellular cancer (HCC) patients on phase I clinical trials in sorafenib era: Analysis of a single institution experience in last 10 years.

e15134 Background: Sorafenib is the only approved systemic therapy in HCC. Clinical trials in HCC often exclude patients with Child-Pugh Stage (CPS) B/C cirrhosis. Furthermore, limited information on outcomes specific to HCC population are reported from early clinical trials. We evaluated the efficacy and safety of early phase clinical trial agents in HCC. Methods: We analyzed 53 Phase I clinical trials that enrolled HCC patients at our institution between 2003–2013. Median progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves along with medians and groups were compared with the log rank test. The magnitude of association and survival was estimated with the hazard ratio (HR). Results: Median age 63 (33–84), males 75 %, ECOG PS 0–1 92%, CPS A 19%, B 71.7% and C 9.4%. 41.5% subjects were treated with prior Sorafenib. Class of agents used included cytotoxics such as microtubule inhibitors (26.4%), anti-folates (5.7%), alkylators (1.9%), topoisomerase inhibitors (...
Abstract 358: Transient Receptor Potential Vanilloid 2 (TRPV2) contributes to myocardial contractility and hypertrophy via sarcoplasmic reticulum calcium handling

Background: TRPV2 is a Ca2+ channel that we have recently discovered in cardiomyocytes. The absence of this channel negatively impacts baseline contractility while stimulation results in a positive inotropic response. What remains to be established is the mechanism of this receptor and its role, if any, in the development of hypertrophy. Methods and Results: We obtained isolated cardiomyocytes from wild type (WT) and TRPV2-/- (KO) mice and found that the sarcoplasmic reticulum Ca2+ content and Ca2+ transients were reduced along with fractional shortening in the KO cardiomyocytes (figure, panels A, B, C). In vivo echocardiography confirmed a decrease in ejection fraction in KO mice in comparison to the WT counterparts (panel D). The relevance of these findings was examined in 6 WT and 5 KO mice subjected to transverse aortic constriction (TAC). These mice were followed by echocardiography weekly for a total of 8 weeks post TAC. At the conclusion, the hearts were obtained for histological and molecular analyses. We demonstrated that the KO mice developed less LV hypertrophy in comparison to WT (via echocardiography and by heart weight/body weight ratios) (figure, panels E and F). Importantly, there was a 5 fold increase in TRPV2 expression assessed by PCR in TAC WT hearts, compared to WT not subjected to TAC (0.72±0.10 vs. 0.13±0.04; p Conclusions: We have discovered a novel cardiac channel that alters Ca2+ cycling and is capable of modulating cardiomyocyte contractility and hypertrophy, which could lead to novel therapeutic options in heart failure and hypertrophy.
Chapter 20 Molecular diversity and cellular functions of neuropeptides

Publisher Summary This chapter discusses the molecular diversity and cellular functions of neuropeptides. The chapter reviews some applications of molecular biological methods to the diversity of peptides made by brain neurons. Some recent studies to examine the interplay between the neuropeptide somatostatin and the classical amine transmitter, acetylcholine on common target neurons in the cerebral cortex, and hippocampal formation are discussed. The chapter discusses the two modern strategies of transmitter discovery. A general molecular discovery strategy involves attacking the molecular specificity of the mature rat and primate brain with a direct examination of the complexity of the genetic messages being expressed there. The interactions among neuropeptides and other transmitters on their shared target cells may represent regulatory mechanisms that are conditional and such conditional signalling mechanisms may set the scales on which other spatial and temporal signals among neurons are manifested as purposeful.
Complexity and naturalness biases in phonotactics: Hayes and White (2013) revisited

Hayes and White (2013) found that English speakers rate words that violate natural phonotactic constraints as worse than words that violate unnatural ones. Their "natural" constraints both enforced typologically common restrictions and were phonetically grounded, while their unnatural constraints met neither criterion. They used this experimental finding as evidence for a learning bias in favor of natural constraints. The strength of this conclusion was weakened by the presence of a confound: the unnatural constraints were also more structurally complex. This paper presents the results from an experiment that replicated Hayes and White, but added complexity as a variable of interest. The results suggest that naturalness and complexity both affect phonological acquisition: supporting the conclusions of Hayes and White (2013), but differing from the findings of most artificial language learning studies.
Timing Binary and Millisecond Pulsars

This tutorial lecture outlines the essentials of making and analyzing timing observations of binary and millisecond pulsars. Many of the necessary procedures are, of course, similar to those used for slow, single pulsars. However, achieving the best attainable timing accuracy for millisecond pulsars requires much tighter tolerances on observing and data-processing procedures, and the presence of orbital motion qualitatively complicates both data acquisition and analysis. In return for adequate diligence in these matters, an observer gains access to a much richer set of measurables than are available for ordinary pulsars. Binary pulsars provide the only experimental handles on the masses of non-accreting neutron stars, and the parameters of their orbits and characteristics of their companion stars provide unique clues on the origin and evolution of the systems. In the most favorable circumstances, significant tests of fundamental physical laws are even possible. Timing data on millisecond pulsars turns out to be valuable for other reasons as well: because they are extremely stable clocks, these objects provide exquisite tools for a wide range of studies in fundamental astrometry, cosmology, gravitation physics, and metrology.
A Literary Method to Exegete Acts 16:11-40, by Considering its Relationship with Euripides Bacchae

This study argues that the author of Luke-Acts made ample use of Euripides Bacchae to fashion his story of Paul’s first missionary activities in Europe as depicted in Acts 16:11-40. The strength of this argument is based on a combination of selective studies done on Acts, which in my opinion if considered collectively represent a compelling interpretation of the book’s intended meaning. The material selected for this analysis will first highlight the social, historical and theological approaches to Acts, which have in the past only marginally provided a glimpse into its meaning. Second, Euripides Bacchae will be compared to Acts 16:11-40 to demonstrate the likelihood that the author of Acts used it as a model for his work. In addition, the theological concerns of which the author of Acts might have considered will be included within the scope of this comparison to support my conclusions on why the author of Acts would be interested in modeling his story after Euripides Bacchae?