cssi/SciSciGPT-SciSciNet huggingface dataset:
Dopamine D4 Receptors Modulate GABAergic Signaling in Pyramidal Neurons of Prefrontal Cortex

Dopaminergic neurotransmission in the prefrontal cortex (PFC) plays an important role in regulating cognitive processes and emotional status. The dopamine D 4 receptor, which is highly enriched in the PFC, is one of the principal targets of antipsychotic drugs. To understand the cellular mechanisms and functional implications of D 4 receptors, we examined the impact of D 4 receptors in PFC pyramidal neurons on GABAergic inhibition, a key element in the regulation of “working memory.” Application of the D 4 agonist N -(methyl)-4-(2-cyanophenyl)piperazinyl-3-methylbenzamide maleate caused a reversible decrease in postsynaptic GABA A receptor currents; this effect was blocked by the D 4 antagonist 3-[(4-[4-chlorophenyl]piperazine-1-yl)methyl]-[1H]-pyrrolo[2,3-b]pyridine but not by the D 2 antagonist sulpiride, suggesting mediation by D 4 receptors. Application of PD168077 also reduced the GABA A receptor-mediated miniature IPSC amplitude in PFC pyramidal neurons recorded from slices. The D 4 modulation of GABA A receptor currents was blocked by protein kinase A (PKA) activation and occluded by PKA inhibition. Inhibiting the catalytic activity of protein phosphatase 1 (PP1) also eliminated the effect of PD168077 on GABA A currents. Furthermore, disrupting the association of the PKA/PP1 complex with its scaffold protein Yotiao significantly attenuated the D 4 modulation of GABA A currents, suggesting that Yotiao-mediated targeting of PKA/PP1 to the vicinity of GABA A receptors is required for the dopaminergic signaling. Together, our results show that activation of D 4 receptors in PFC pyramidal neurons inhibits GABA A channel functions by regulating the PKA/PP1 signaling complex, which could underlie the D 4 modulation of PFC neuronal activity and the actions of antipsychotic drugs.
A biomechanical hypothesis explaining upstream movements by the freshwater snail Elimia

1. Many taxa of freshwater invertebrates show active upstream movements, particularly the snails. Hypotheses explaining this behaviour invoke the search for food or space, compensation for drift, avoidance of predation and hydrodynamic effects. The pervasiveness of upstream movements among remote lineages of snails (two subclasses, three orders, 10 families), however, suggests that snails may move upstream for mechanical rather than adaptive reasons. 2. It is proposed that upstream movements by snails are a function of torque on the snail’s foot generated by hydrodynamic drag on the shell. When subject to high broadside drag-forces on their shells, snails are able to reduce torque and stabilize orientation only by directing their anterior aspect upstream. 3. Movements of the freshwater pleurocerid snail Elimia were studied by following marked free-ranging individuals in six streams in Alabama, USA (four species, eight populations). 4. Populations showed either no net movement (two streams) or significant upstream movements ranging to a mean of ≈40 m over a 3-month period (four streams). Movement patterns were stream specific rather than species or population specific. Within populations showing significant upstream movements, snails with shell lengths ≤10 mm showed little net movement. Larger snails showed movements from 0 to >200 m upstream. 5. A torque-constrained random walk model was used to perform a post hoc test of the hypothesis that upstream movements were a function of torque on the snail’s foot generated by hydrodynamic drag on the shell. The model predicted upstream and size-dependent movement patterns that approximated those observed for snails in the field.
Methodology for Evaluating Security Controls Based on Key Performance Indicators and Stakeholder Mission

Information security continues to evolve in response to disruptive changes with a persistent focus on information-centric controls and a healthy debate about balancing endpoint and network protection, with a goal of improved enterprise/business risk management. Economic uncertainty, intensively collaborative styles of work, virtualization, increased outsourcing and ongoing compliance pressures require careful consideration and adaptation. This paper proposes a Cyberspace Security Econometrics System (CSES) that provides a measure (i.e., a quantitative indication) of reliability, performance and/or safety of a system that accounts for the criticality of each requirement as a function of one or more stakeholders’ interests in that requirement. For a given stakeholder, CSES accounts for the variance that may exist among the stakes one attaches to meeting each requirement. This paper introduces the basis, objectives and capabilities for the CSES including inputs/outputs as well as the structural and mathematical underpinnings.
Decision making among Veterans with incidental pulmonary nodules: A qualitative analysis

Summary Purpose Among patients undergoing lung cancer evaluation for newly diagnosed, incidental pulmonary nodules, it is important to evaluate the shared power and responsibility domain of patient-centered communication. We explored Veterans' perceptions of decision making with regards to an incidentally-detected pulmonary nodule. Methods We conducted semi-structured, qualitative interviews of 19 Veterans from one medical center with incidentally-detected pulmonary nodules that were judged as having a low risk for malignancy. We used qualitative description for the analysis, focusing on patients' perceptions of shared decision making with their primary care provider (PCP). Interviews were conducted in 2011 and 2012. Results Patients almost always played a passive role in deciding how and when to evaluate their pulmonary nodule for the possibility of malignancy. Some patients felt comfortable with this role, expressing trust that their clinician would provide the appropriate care. Other patients were not satisfied with how these decisions were made with some expressing concern that no decisions had actually occurred. Regardless of how satisfied they were with the decision, patients did not report discussing how they liked to make decisions with their PCP. Conclusions Veterans in our study did not engage in shared decision making with their clinician. Some were satisfied with this approach although many would have preferred a shared approach. In order to reduce patient distress and improve satisfaction, clinicians may want to consider adopting a shared approach when making decisions about pulmonary nodule evaluation.
Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist

Erythema multiforme (EM) is an uncommon, immune-mediated disorder that presents with cutaneous or mucosal lesions or both. In herpes simplex virus (HSV)‐associated EM, the findings are thought to result from cell-mediated immune reaction against viral antigenpositive cells that contain the HSV DNA polymerase gene (pol). The target lesion, with concentric zones of color change, represents the characteristic cutaneous finding seen in this disorder. Although EM can be induced by various factors, HSV infection continues to be the most common inciting factor. Histopathologic testing and other laboratory investigations may be used to confirm the diagnosis of EM and to differentiate it from other clinical imitators. Imitators of EM include urticaria, Stevens-Johnson syndrome, fixed drug eruption, bullous pemphigoid, paraneoplastic pemphigus, Sweet’s syndrome, Rowell’s syndrome, polymorphus light eruption, and cutaneous small-vessel vasculitis. Because disease severity and mucosal involvement differ among patients, treatment should be tailored to each patient, with careful consideration of treatment risk vs benefit. Mild cutaneous involvement of EM can be managed primarily with a goal of achieving symptomatic improvement; however, patients with HSV-associated recurrent EM and idiopathic recurrent EM require treatment with antiviral prophylaxis. Inpatient hospitalization may be required for patients with severe mucosal involvement that causes poor oral intake and subsequent fluid and electrolyte imbalance. With this review, we strive to provide guidance to the practicing dermatologist in the evaluation and treatment of a patient with EM.
Influence of neighborhood-level factors on social support in early-stage breast cancer patients and controls.

Abstract Rationale Low social support has been linked to negative health outcomes in breast cancer patients. Objective We examined associations between perceived social support, neighborhood socioeconomic deprivation, and neighborhood-level social support in early-stage breast cancer patients and controls. Methods This two-year longitudinal study in the United States included information collected from telephone interviews and clinical records of 541 early-stage patients and 542 controls recruited from 2003 to 2007. Social support was assessed using the Medical Outcomes Study Social Support Survey (MOS-SS). Residential addresses were geocoded and used to develop measures including neighborhood social support (based on MOS-SS scores from nearby controls) and neighborhood socioeconomic deprivation (a composite index of census tract characteristics). Latent trajectory models were used to determine effects of neighborhood conditions on the stable (intercept) and changing (slope) aspects of social support. Results In a model with only neighborhood variables, greater socioeconomic deprivation was associated with patients' lower stable social support (standardized estimate = −0.12, p = 0.027); neighborhood-level social support was associated with social support change (standardized estimate = 0.17, p = 0.046). After adding individual-level covariates, there were no direct neighborhood effects on social support. In patients, neighborhood socioeconomic deprivation was associated with support indirectly through marriage, insurance status, negative affect, and general health. In controls, neighborhood socioeconomic deprivation was associated with support indirectly through marriage ( p Conclusion Indirect effects of neighborhood socioeconomic deprivation on social support differed in patients and controls. Psychosocial and neighborhood interventions may help patients with low social support, particularly patients without partnered relationships in deprived areas.
In Situ Ambient Pressure X-ray Photoelectron Spectroscopy of Cobalt Perovskite Surfaces under Cathodic Polarization at High Temperatures

Heterostructured oxide interfaces have demonstrated enhanced oxygen reduction reaction rates at elevated temperatures (∼500–800 °C); however, the physical origin underlying this enhancement is not well understood. By using synchrotron-based in situ ambient pressure X-ray photoelectron spectroscopy (APXPS), we focus on understanding the surface electronic structure, elemental composition, and chemical nature of epitaxial La0.8Sr0.2CoO3−δ (LSC113), (La0.5Sr0.5)2CoO4±δ (LSC214), and LSC214-decorated LSC113 (LSC113/214) thin films as a function of applied electrical potentials (0 to −800 mV) at 520 °C and p(O2) of 1 × 10–3 atm. Shifts in the top of the valence band binding energy and changes in the Sr 3d and O 1s spectral components under applied bias reveal key differences among the film chemistries, most notably in the degree of Sr segregation to the surface and quantity of active oxygen sites in the perovskite termination layer. These differences help to identify important factors governing the enhanced ac...
A Simulation Framework for Aerospace Design Education

Most undergraduate programs in aerospace engineering culminate with a capstone design sequence. This course series integrates theoretical topics and applies them to relevant design problems. One difficulty that arises in teaching the design series is finding a framework or theme that makes the interdependencies of the aerospace sub-disciplines readily apparent. Without such a framework, the course topic sequence can resemble a long list of seemingly unrelated review material gathered from aerodynamics, structures, propulsion and flight control textbooks. This paper offers flight trajectory simulation as a framework for aerospace design education. The guiding principal is to build single-use simulation models to resolve design issues and verify analytical predictions. The paper first reviews the three degree-of-freedom equations of motion that provide a basis for the simulation framework. Example problems are then provided for both aircraft and spacecraft design. The paper concludes with a summary of classroom activities and instructor experience.
The yield of colonic biopsy in the evaluation of chronic unexplained diarrhea.

Background and aims In clinical practice, colonoscopy is widely used for the workup of chronic unexplained diarrhea. The aim of this study was to determine the yield of colonic biopsy in such an endeavor. Methods In a computerized database of 130 204 patients evaluated for chronic diarrhea, we tested the influence of biopsy site, number of tissue fragments, patient symptoms, and indication on the outcome of histopathologic evaluation. Results The population comprised 69% women and 31% men aged (mean±SD) 52.8±17.4 years. In 19% of patients, histopathological analysis revealed various types of mucosal lesion, the most common being microscopic colitis (8.6%), ulcerative colitis (2.2%), Crohn's disease (0.6%), active colitis (5.0%), diverticulitis (0.1%), and colonic ischemia (0.5%). In 29% of patients, the colonoscopy also revealed the presence of colon polyps. Endoscopists tended to take significantly more tissue samples from endoscopically visible lesions than for random biopsies of macroscopically normal-appearing mucosa. Conclusion Overall, these associations suggest that specific diagnoses lead to more biopsies, rather than more biopsies leading to more diagnoses. Colonoscopy is a successful tool in the workup of chronic diarrhea, yielding a definitive diagnosis in almost one-fifth of all patients. As an added benefit, it also contributes to cancer prevention through the incidental findings of colonic neoplasm.
Implementation of recursive shift-invariant flow graphs in parallel/pipelined processing environments

The objective of the research reported in this thesis is to develop a set of techniques to automatically find rate optimal or near rate optimal implementations in parallel/pipelined processing environments for DSP algorithms that are represented by recursive shift-invariant flow graphs. The parallel/pipelined processing environments are synchronous parallel processing systems that consist of one or more processors where each processor could be internally pipelined. The shift-invariant flow graph is a graphical representation which describes the computational structures of broad class of DSP algorithms at fine-grain level. Since the node execution times in defining flow graphs are deterministic, this research addresses compile time scheduling. The research in this thesis can be divided into three areas. First, an instruction scheduling methodology for a single pipelined processor is presented. In such case, the problem to be addressed is the scheduling of a single instruction stream which controls all of the pipeline stages. The goal of an automatic scheduler in this context is to rearrange the order of instructions such that they are executed with minimum time and no pipeline faults. In other words, sequences of instructions are ordered to minimize the iteration period between successive iteration of defining flow graphs. Second, a new class of multiprocessor system, called Clock-Skewed Parallel Processing system, is proposed. This system provides an elegant solution to interprocessor communication problems multiprocessor system. The interprocessor communication strategy described in this system is a combination of a synchronous multiprocessor architecture, an associated interprocessor communication architecture, and a multiprocessor compiler which considers the interprocessor communication to be a scheduling constraint. This system not only can handle the interprocessor communications very efficiently but also can explicitly incorporate the interprocessor communication time delay into the parallel scheduling model. Third, an instruction scheduling methodology for a multiple pipelined processing system is presented. In this system, since more than one pipelined processor is involved in parallel processing, all the processors must be interconnected in some manner. In such processing environments, the interprocessor communications joins the instruction scheduling as a major problem. This research presents a system scheduler which combines the instruction scheduling methodology for a single pipelined processor and the interprocessor communication strategy in the clock-skewed parallel processing system. This system has a simple interprocessor communication structure which can provide good performance and which results in scheduling constraints that can be reasonably integrated into the searching algorithms of an optimal compiler.
Interface Based Memory Synthesis of Image Processing Applications in FPGA

Image processing applications are computationally intensive and data intensive and rely on memory elements (buffer, window, line buffer, shift register, and frame buffer) to store data flow dependencies between computing components in FPGA. Due to the limited availability of these resources, optimization of memory allocation and the implementation of efficient memory architectures are important issues. We present an interface, the Component Interconnect and Data Access (CIDA), and its implementation, based on interface automata formalism. We used that interface for modeling image processing applications and generating common memory elements. Based on the proposed model and information about the FPGA architecture, we also present an optimization model to achieve allocation memory requirements to embedded memories (Block RAM and Distributed RAM). Allocation results from realistic video systems on Xilinx Zynq FPGAs verify the correctness of the model and show that the proposed approach achieves appreciable reduction in block RAM usage.
Supporting real-time wireless traffic through a high-throughput side channel

Performance of modern cognitive and interactive mobile applications highly depends on the data transmission delay in the wireless link that is vital to supporting real-time wireless traffic. To eliminate wireless network congestion caused by large amounts of concurrent network traffic and support such real-time traffic, traditional schemes adopt various flow control and QoS-aware traffic scheduling techniques, but fail when the amount of network traffic further increases. In this paper, we present a novel design of high-throughput wireless side channel, which operates concurrently with the existing wireless network channel over the same spectrum but dedicates to real-time traffic. Our key idea of realizing such a side channel is to exploit the excessive SNR margin in the wireless network to encode data as patterned interference. We design such patterned interference in form of energy erasure over specific subcarriers in an OFDM-based wireless network, and achieve a data rate of 1.25 Mbps in the side channel without affecting the existing wireless network links. Experimental results over software-defined radio platforms demonstrate the effectiveness of our side channel design in reducing the latency of real-time wireless traffic, while providing sufficient data throughput for such traffic.
The Characterological Imperative: On Heckman, Humphries, and Kautz's The Myth of Achievement Tests: The GED and the Role of Character in American Life

James J. Heckman, John Eric Humphries, and Tim Kautz make a powerful case for noncognitive skills--or what they conceptualize as character--as an explanation of educational achievement and other important outcomes in life. They do so while exposing the myth of the GED, arguing that the GED harms its intended beneficiaries by failing to instill the character skills that predict adult success. Childhood interventions to build personal character, especially self-control, are emphasized. The Myth of Achievement Tests is a major contribution, but I integrate relevant research on crime and social control across the life course that motivates a more dynamic conceptualization of character. I also review evidence on the environment as a source of both cognitive and noncognitive skills, including exposure to concentrated deprivation, violence, and lead toxicity. Moreover, I review evidence suggesting that social reactions to character shape life chances in ways not reducible to individual propensities, such as changes in criminal-justice policy that created large cohort differentials in incarceration for the same underlying behaviors. Social context and the character of American society itself are thus central to fostering individual character--not just skills but the desire to conform. It follows that self-control and social control need to be better unified theoretically and in designing interventions.
Gypsum and Gypsum Products

This chapter discusses that the use of gypsum to control setting in Portland cement accounts for considerable quantities of the use of this material. Control of the reaction rate of tricalcium aluminate, the constituent of cement that reacts most rapidly with water, is most commonly achieved through the addition of gypsum to commercial portland cement. This material is normally added to the cement clinker before grinding. The cement manufacturers usually specify a sulfur trioxide content of about 36%. Excess sulfate in the form of hemihydrate can cause flash set in portland cement. Gypsum wallboard is widely used in the North American housing industry. Dehydration of the gypsum often results in the formation of a mixture of hemihydrate and anhydrite. All plasters eventually revert to gypsum on setting, the rate of transformation being dependent on the conditions of calcination. Gypsum has useful fire-resistant properties due to its water of crystallization. Gypsum plaster is widely used as an insulating material for protecting columns and beams of wooden materials from the high temperatures during a fire.
MUSSE: A designed multi-ultrasonic-sensor system for echolocation on multiple robots

This paper presents a multi-ultrasonic-sensor system designed for Simultaneous Localization and Mapping (SLAM) on the open source robot Kobuki Turtlebot. The operating system used in this research project, Robot Operating System (ROS), is also an open source project initially released in 2007. Our system has reduced response time and lower cost than traditional laser sensors. It consists of 8 HY-SRF05 rangers that can work sequentially on an embedded system such as a Raspberry Pi. The communication between the embedded system and the robot is achieved with a Python package that communicates via local TCP/IP. Our multi-sensor structure can be applied to a multi-agent system, composed of 3 identical robots. Our results from preliminary experiments show the possibility of conducting SLAM using our designed system. By implementing this improved design on a multi-agent system, the SLAM process can be conducted more efficiently and accurately than a single robot with a laser sensor.
CXCR4 Gene Dosage Is Critical for HSC Engraftment

Abstract Introduction: Warts, Hypogammaglobulinemia, Infections and Myelokathexis Syndrome (WHIMS) is an autosomal dominant immunodeficiency resulting from gain-of-function mutations in the chemokine receptor CXCR4. We recently described a unique WHIMS patient who underwent spontaneous genetic and phenotypic reversion at approximately age 30 after being severely affected as a child. Her reversion was due to a single catastrophic genetic event known as chromothripsis (chromosome shattering) resulting in the deletion of one copy of 163 genes in addition to her mutant copy of CXCR4 on chromosome 2. This event was traced to a hematopoietic stem cell (HSC) that had spontaneously repopulated her bone marrow; however, which of the genes was responsible and the mechanism required further investigation. Methods: Mouse models of CXCR4 haploinsufficiency (Cxcr4+/o) and WHIMS (Cxcr4+/S338X) were used in competitive bone marrow repopulation experiments transplanting whole bone marrow cells or purified HSC. Recipient mice were treated with / without lethal irradiation prior to transplant. Genome editing with TALENs and CRISPR-Cas9 technology was used to target CXCR4 for deletion in human cell lines. Results: Cxcr4 haploinsufficiency markedly enhanced HSC engraftment potential in recipient WHIM mice whether the donor HSC were purified from whole bone marrow cells or not, and whether the recipient was conditioned by lethal irradiation or not. Enhanced engraftment by Cxcr4 haploinsufficient donor HSC also occurred in wild-type mouse recipients, but to a lesser extent, and was also HSC intrinsic. Genome editing experiments have been successful at deleting one or both copies of CXCR4 in human cell lines in up to 40% of treated cells, and in reducing CXCR4 surface expression. Conclusion: While CXCR4 was already understood to be important in HSC biology, this patient and subsequent murine experiments have proven that the gene dosage of CXCR4 is a critical factor affecting HSC engraftment. Genome editing is a promising technology for deleting one copy of CXCR4, ideally the WHIM allele,in autologous HSC as a strategy to cure WHIM syndrome. Disclosures McDermott: US National Institutes of Health: Employment, Patents & Royalties: pending. Jacobs: US National Institutes of Health: Employment, Patents & Royalties: pending. Liu: US National Institutes of Health: Employment, Patents & Royalties: pending. Gao: US National Institutes of Health: Employment, Patents & Royalties: pending. Murphy: US National Institutes of Health: Employment, Patents & Royalties: pending.
Modeling mechanical properties of polyhydroxyalkanoate during degradation in animal tissue

Polyhydroxyalkanoates (PHAs) are a family of biodegradable and biocompatible polymers produced by several species microorganisms that possess favorable mechanical properties (e.g. strength and elongation properties). Different types of PHA polymers have been used in medical applications. However, in order to better understand the use of this polymer in the different applications, a thorough understanding of the kinetics of in vivo degradation is one of the major requirements. In this study, poly(3-hydroxybutyrate) (PHB) was subcutaneously implanted in mice and incubated for 2, 4, 8, or 16 weeks. After removal from the animal, the strength, elongation, mass loss, and enthalpy of the PHB were tested for each time point. From these data, a mathematical model was generated by Rayleigh's method of dimensional analysis, where polymer strength over tissue contact time could be predicted. To prove the model, previous data obtained by our group were used: poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] incubation in the presence of human embryonic kidney cells (HEK). It was found that the developed model was aligned with experimental results, could predict the strength of the polymer when in contact with cells, and the predicted strength follows the trend of the experimental data. Also, the dimensionless constant (K) value associated with the model is different for both experiments, where this constant, produced via experimental data, is used for construction of a homogeneous equation. Copyright © 2017 John Wiley & Sons, Ltd.
Heparanase: Potential roles in multiple sclerosis.

Abstract Heparanase is a heparan sulfate degrading enzyme that cleaves heparan sulfate (HS) chains present on HS proteoglycans (HSPGs), and has been well characterized for its roles in tumor metastasis and inflammation. However, heparanase is emerging as a contributing factor in the genesis and severity of a variety of neurodegenerative diseases and conditions. This is in part due to the wide variety of HSPGs on which the presence or absence of HS moieties dictates protein function. This includes growth factors, chemokines, cytokines, as well as components of the extracellular matrix (ECM) which in turn regulate leukocyte infiltration into the CNS. Roles for heparanase in stroke, Alzheimer's disease, and glioma growth have been described; roles for heparanase in other disease such as multiple sclerosis (MS) are less well established. However, given its known roles in inflammation and leukocyte infiltration, it is likely that heparanase also contributes to MS pathology. In this review, we will briefly summarize what is known about heparanase roles in the CNS, and speculate as to its potential role in regulating disease progression in MS and its animal model EAE (experimental autoimmune encephalitis), which may justify testing of heparanase inhibitors for MS treatment.
Pilgrim Assurance Building

SUBJECT AREAS: Bids, Analysis, Hedge funds, Investments. A local real estate developer has to decide how much to bid for a Boston office building in 2005.
Improvements in electron-photon-relaxation data for MCNP6

After the initial release of the first production version of MCNP6 and its subsequent beta release, the extended electron-photon-relaxation capabilities of the code have continued to be developed. With the availability of newer data, several enhancements and corrections to the methods have been installed into the code. In this paper we discuss these improvements, including the development of three distinct approaches to sampling electron elastic scattering, the correction of an earlier data resolution problem, and a few formal corrections to the earlier ACE data file.
TFEB regulates lysosomal positioning by modulating TMEM55B expression and JIP4 recruitment to lysosomes

Lysosomal distribution is linked to the role of lysosomes in many cellular functions, including autophagosome degradation, cholesterol homeostasis, antigen presentation, and cell invasion. Alterations in lysosomal positioning contribute to different human pathologies, such as cancer, neurodegeneration, and lysosomal storage diseases. Here we report the identification of a novel mechanism of lysosomal trafficking regulation. We found that the lysosomal transmembrane protein TMEM55B recruits JIP4 to the lysosomal surface, inducing dynein-dependent transport of lysosomes toward the microtubules minus-end. TMEM55B overexpression causes lysosomes to collapse into the cell center, whereas depletion of either TMEM55B or JIP4 results in dispersion toward the cell periphery. TMEM55B levels are transcriptionally upregulated following TFEB and TFE3 activation by starvation or cholesterol-induced lysosomal stress. TMEM55B or JIP4 depletion abolishes starvation-induced retrograde lysosomal transport and prevents autophagosome-lysosome fusion. Overall our data suggest that the TFEB/TMEM55B/JIP4 pathway coordinates lysosome movement in response to a variety of stress conditions.
The Multifaceted Impact of Peroxiredoxins on Aging and Disease.

Abstract Significance: Peroxiredoxins (Prxs), a family of thiol-associated peroxidases, are purported to play a major role in sensing and managing hydrogen peroxide concentrations and transducing peroxide-derived signals. Recent Advances: Prxs can act as detoxifying factors and impart effects to cells that can be either sparing or suicidal. Advances have been made to address the qualitative changes in Prx function in response to quantitative changes in the signal level and to understand how Prx activity could be affected by their own substrates. Here we rationalize the basis for both positive and negative effects on signaling pathways and cell physiology, summarizing data from model organisms, including invertebrates. Critical Issues: Resolving the relationship between the promiscuous behavior of reactive oxygen species and the specificity of Prxs toward different targets in redox-sensitive signaling pathways is a key area of research. Attempts to understand Prx function and underlying mechanisms were con...
Overview and Historical Evolution

One of the dreams in the characterization of materials is to be able to identify and determine the positions of all the atoms in a material with atomic precision. The technique of atom probe tomography permits this dream to be realized.
Acute and Chronic Control of Colonic Chloride Secretion by Mast Cell Mediators

Publisher Summary This chapter focuses on acute and chronic control of colonic chloride secretion by mast cell mediators. The chapter discusses those facets of immune-related intestinal secretion that are likely to be mediated, at least in part, by direct effects of mast cell mediators on the properties of the epithelium. Mast cells produce a very wide range of substances when activated by the combination of antigen with membrane-bound IgE. Among these mediators are substances that are stored in the granules and released by a process of degranulation. Mediators in this class include histamine, proteoglycans such as heparin and chondroitin sulfate, and a variety of proteolytic enzymes. Mast cells also have the capacity to synthesize mediators de novo once activated. Mast cell mediators may induce secretion at the intracellular level by a variety of mechanisms. In common with other prostaglandins, prostaglandin D2 (PGD2) is thought to act by increasing cellular levels of cAMP.
The Role of Geotechnics in Addressing New World Problems

There are many “new world”, or recently emergent, global challenges whose solutions require geotechnical inputs. Included among these challenges are climate change, enhancement of urban sustainability and resilience, energy and materials resource management, and management of water resources. Fundamental advances in the understanding of soil and rock properties and behavior, coupled with advances in sensing, monitoring and modeling of geo-systems, are needed for solutions to be found or implemented satisfactorily in each of these four areas. In addition, there is need for fundamental research that can improve the subsurface characterization and monitoring of complex geo-material behavior, the handling of multi-faceted, multi-scale geotechnical and geo-environmental processes, the integration of “big-data” and data-science methods into geotechnical engineering research and practice, and the management of uncertainty and risk. In addition to advancing fundamental research in geotechnics, geotechnical engineers also need to lend expertise and leadership to the interdisciplinary research and development efforts that are essential to ensuring our sustainable future.
Si-Based 94-GHz Phased Array Transmit and Receive Modules for Real-Time 3D Radar Imaging

Compact phased array transmitter (TX) and receiver (RX) modules operating at 94 GHz are presented and demonstrated in a 3D radar imaging system. Each module consists of four SiGe ICs and a package that integrates 8X8 dual-polarized antennas and 10-GHz IF power combiners. Each TX and RX IC integrates beam-forming, frequency conversion, LO generation, and digital control functions. The modules have beam steering capabilities in both azimuth and elevation over a range of +/- 32 degrees. A radar imaging system is implemented comprising an evaluation board with one TX module and one RX module, FMCW signal generation and acquisition components, and an FPGA for fast beam steering control. The system can steer TX and RX beams to a given direction and perform a radar measurement in that direction in less than 100us, enabling 3D imaging in real time. Measurement results are presented for the modules and the prototype imaging system.
Emerging Insights and Interventions for Diabetic Retinopathy

To introduce recent advances in the understanding of diabetic retinopathy and to summarize current and emerging strategies to treat this common and complex cause of vision loss. Advances in retinal imaging and functional analysis indicate that retinal vascular and neural pathologies exist long before the development of clinically visible retinopathy. Such diagnostics could facilitate risk stratification and selective early intervention in high-risk patients. Antagonists of the vascular endothelial growth factor pathway effectively reduce vision loss in diabetes and promote regression of disease severity. Promising new strategies to treat diabetic retinopathy involve novel systemic diabetes therapy and ocular therapies that antagonize angiogenic growth factor signaling, improve blood-retina barrier function and neurovascular coupling, modulate neuroretinal metabolism, or provide neuroprotection. Long considered a pure microvasculopathy, diabetic retinopathy in fact affects the neural and vascular retina as well as neurovascular communication. Emerging therapies include those that target neuroretinal dysfunction in addition to those modulating vascular biology.
The Practice of Suicide Assessment and Management by Marriage and Family Therapists

AbstractOver 90% of mental health providers encounter suicidal clients. However, the majority of marriage and family therapists (MFTs) are not exposed to suicide-specific trainings within their cli...
Rabies virus epitopic variation: use in ecologic studies.

Publisher Summary People living in the industrialized societies of Europe and North America are less at risk from dying of rabies than of being struck by lightning.. Before dismissing rabies as a trivial public health problem, however, it must be noted that the low incidence of human rabies is not the consequence of disease eradication; rather it is the result of control programs comprising massive preexposure and postexposure prophylaxis and dog immunization. Recent advances in vaccine technology have suggested new avenues of rabies control that, in addition to preventing human infection, may also actually eradicate the disease from its animal reservoir, thus eliminating the need for human and domestic animal prophylaxis. Oral vaccination of red foxes by field baiting has dramatically reduced rabies in some European countries and may have eliminated it from some areas.
‘We have to be a little more realistic’: women’s outdoor recreation experiences in a community hiking group

Grounded in the theoretical framework of ecological feminism, this study explores the tension between constraint and empowerment that often marks women’s participation in outdoor recreation. Drawin...
Enhancement of Opioid Antinociception by Nicotinic Ligands

Nicotine has previously been shown to augment the antinociceptive effects of μ-opioid agonists in squirrel monkeys without producing a concomitant increase in behavioral disruption. The present studies were conducted to extend these findings by determining the ability of the nicotinic acetylcholine receptor (nAChR) agonist epibatidine and partial α4β2 nAChR agonist varenicline to selectively augment the antinociceptive effects of the μ-opioid receptor (MOR) full agonist fentanyl, the MOR partial agonist nalbuphine, and the κ-opioid receptor (KOR) agonist U69,593 in male squirrel monkeys. Results indicate that both nAChR ligands selectively increased the antinociceptive effects of nalbuphine and that epibatidine increased the antinociceptive effects of U69,593 without altering effects on operant behavior. However, neither epibatidine nor varenicline enhanced the antinociceptive effects of fentanyl, perhaps due to its high efficacy. The enhancement of nalbuphine's antinociceptive effects by epibatidine, but not varenicline, could be antagonized by either mecamylamine or dihydro-β-erythroidine, consistent with α4β2 mediation of epibatidine's effects but suggesting the involvement of non-nAChR mechanisms in the effects of varenicline. The present results support previous findings showing that an nAChR agonist can serve as an adjuvant for MOR antinociception and, based on results with U69,593, further indicate that the adjuvant effects of nAChR drugs may also apply to antinociception produced by KOR. Our findings support the further evaluation of nAChR agonists as adjuvants of opioid pharmacotherapy for pain management and point out the need for further investigation into the mechanisms by which they produce opioid-adjuvant effects. SIGNIFICANCE STATEMENT: Nicotine has been shown to augment the antinociceptive effects of μ-opioid receptor analgesics without exacerbating their effects on operant performance. The present study demonstrates that the nicotinic acetylcholine receptor (nAChR) agonist epibatidine and partial α4β2 nAChR agonist varenicline can also augment the antinociceptive effects of nalbuphine, as well as those of a κ-opioid receptor agonist, without concomitantly exacerbating their behaviorally disruptive effects. These findings support the view that nAChR agonists and partial agonists may have potential as adjuvant therapies for opioid-based analgesics.
Risk factors for pediatric surgical site infection following neurosurgical procedures for hydrocephalus: a retrospective single-center cohort study

Infection is a major complication following cerebral spinal fluid (CSF) diversion procedures for hydrocephalus. However, pediatric risk factors for surgical site infection (SSI) are currently not well defined. Because a SSI prevention bundle is increasingly introduced, the purpose of this study was to evaluate risk factors associated with SSIs following CSF diversion surgeries following a SSI bundle at a single quaternary care pediatric hospital. We performed a retrospective cohort study of patients undergoing CSF diversion procedures from 2017 to 2019. SSIs were identified prospectively through continuous surveillance. We performed unadjusted logistic regression analyses and univariate analyses to determine an association between SSIs and patient demographics, comorbidities and perioperative factors to identify independent risk factors for SSI. We identified a total of 558 CSF diversion procedures with an overall SSI rate of 3.4%. The SSI rates for shunt, external ventricular drain (EVD) placement, and endoscopic third ventriculostomy (ETV) were 4.3, 6.9 and 0%, respectively. Among 323 shunt operations, receipt of clindamycin as perioperative prophylaxis and presence of cardiac disease were significantly associated with SSI (O.R. 4.99, 95% C.I. 1.27–19.70, p = 0.02 for the former, and O.R. 7.19, 95% C.I. 1.35–38.35, p = 0.02 for the latter). No risk factors for SSI were identified among 72 EVD procedures. We identified receipt of clindamycin as perioperative prophylaxis and the presence of cardiac disease as risk factors for SSI in shunt procedures. Cefazolin is recommended as a standard antibiotic for perioperative prophylaxis. Knowing that unsubstantiated beta-lactam allergy label is a significant medical problem, efforts should be made to clarify beta-lactam allergy status to maximize the number of patients who can receive cefazolin for prophylaxis before shunt placement. Further research is needed to elucidate the mechanism by which cardiac disease may increase SSI risk after shunt procedures.
Issues in Higher Education and Science, Technology, Engineering, and Mathematics (STEM)

In the science, technology, engineering, and mathematics (STEM) fields, students often struggle with content while adjusting to the college experience, and underrepresented students often encounter additional challenges (Nelson, 2007; Martin, Stefl, Cain, & Pfirman, 2020; Leary, Morewood, & Bryner, 2020). Higher education institutions strive to help students experiencing these difficulties succeed and have positive educational experiences. Researchers find that supportive advising, culturally inclusive programming, mentoring, and strategic support systems can improve retention and enhance the student experience during college (Astin, 1993; Seidman, 2012; Castellanos & Jones, 2003; Kuh, Schneider, & Association of American Colleges and Universities, 2008; Renn & Arnold, 2003; Tinto, 1993; Nerio, Webber, MacLachlan, Lopatto, & Caplan, 2019, Leary, Morewood, & Bryner, 2020).
A longitudinal workplace-based interprofessional curriculum for graduate learners in a geriatrics patient-centered medical home

Abstract Current health professions training programs offer limited longitudinal opportunities in geriatrics and interprofessional collaborative practice (IPCP); these longitudinal opportunities are necessary for a workforce capable of caring for an aging population with complex care needs. We designed a year-long, workplace-based curriculum incorporating interprofessional (IP) preceptorships and formal conferences in which graduate learners from geriatric medicine, pharmacy, social work, and law formed a learners’ team, learned about IPCP, and cared for older adults in an academic geriatrics patient-centered medical home. Our curricular objectives were to 1) improve IP collaborative competencies, 2) improve perceived teamness (defined as having core IP qualities of a team), and 3) provide team-based care to older adults. Our evaluation included learners' self-assessment on IP core competencies, perceived teamness, and the older adults' and their families’ perceptions on their team-based care. Learners reported improvement in IP collaborative competencies (P
Ion implantation for figure correction of thin X-ray telescope mirror substrates

Figure correction of X-ray telescope mirrors will be critical for future missions that require high angular resolution and large collecting areas. In this paper, we show that ion implantation offers a method of correcting figure errors by imparting sub-surface in-plane stress in a controllable magnitude and location in Schott D-263 glass, Corning Eagle XG glass, and crystalline silicon substrates. In addition, we can in theory achieve nearly exact corrections in Schott D-263 glass, by controlling the direction of the stress. We show that sufficient stress may be applied to Schott D-263 glass to achieve figure correction in mirrors with simulated initial figure errors. We also report on progress of a system that will be capable of correcting conical shell mirror substrates.
Beyond the Data Deluge

The demands of data-intensive science represent a challenge for diverse scientific communities.
Subnormal subgroups of the groups of rational points of reductive algebraic groups

We prove that for a reductive algebraic group G over an infinite field K, the group of rational points G(K) does not contain any noncentral finitely generated normal subgroups.
Practical implications of educational background on future corporate exceutives' social responsibility orientation

Differences between business students atsecular and non-secular universities withregard to their corporate social responsibilityorientation (CSRO) are examined. The resultsshow that the two groups' attitudes toward thefour components of CSRO are significantlydifferent. Specifically, compared to businessstudents in non-secular institutions, thestudents of secular universities exhibitgreater concern about the legal component ofcorporate responsibility and a weakerorientation toward discretionary activities. Nosignificant differences between the two groupswere observed with respect to economicperformance and the ethical dimension.Explanations as well as limited generalizationsand implications are developed.
How Good were those Probability Predictions? The Expected Recommendation Loss (ERL) Scoring Rule

We present a new way to understand and characterize the choice of scoring rule (probability loss function) for evaluating the performance of a supplier of probabilistic predictions after the outcomes (true classes) are known. The ultimate value of a prediction (estimate) lies in the actual utility (loss reduction) accruing to one who uses this information to make some decision(s). Often we cannot specify with certainty that the prediction will be used in a particular decision problem, characterized by a particular loss matrix (indexed by outcome and decision), and thus having a particular decision threshold. Instead, we consider the more general case of a distribution over such matrices. The proposed scoring rule is the expectation, with respect to this distribution, of the loss that is actually incurred when following the decision recommendation, the latter being the decision that would be considered optimal if we were to assume the predicted probabilities. Logarithmic and quadratic scoring rules arise from specific examples of these distributions, and even common single-threshold measures such as the ordinary misclassification score obtain from degenerate special cases.