cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1483: MT-3724, an engineered toxin body targeting CD20 for non-Hodgkin's lymphoma

Molecular Templates has developed engineered toxin bodies (ETBs), potent recombinant immunotoxins that combine the specificity of an antibody fragment with the powerful direct cytotoxicity of the Shiga-like toxin A subunit to specifically destroy target expressing cells. The use of other immunotoxins and antibody-drug conjugates is limited to targets with tumor-specific cell surface expression that efficiently internalize. The ETB scaffold has been designed to overcome this limitation and promote forced internalization of ETBs, a property that expands the potential targets to receptors with poor internalization kinetics. An additional benefit to ETBs is the mechanism of action (MOA) which is unique to that of other oncology treatments. CD20, a receptor that does not undergo rapid internalization, is a well characterized target for agents used to treat non-Hodgkin9s lymphoma (NHL). Thus, successful CD20-targeted clinical strategies include monoclonal antibodies (mAbs) and radiolabeled mAbs that act on the cell surface. Molecular Templates’ lead compound, MT-3724, is a CD20-targeted ETB that has been engineered to force the rapid internalization of the immunotoxin after binding to CD20. MT-3724 has potent direct cell kill activity on CD20 positive lymphoma cells and is the first immunotoxin to CD20 to enter the clinic. The on-going phase I study being conducted at Memorial Sloan-Kettering Cancer Center, MD Anderson Cancer Center, and New York University Langone Medical Center has shown promising safety and efficacy in highly refractory NHL patients. Once MT-3724 is delivered to appropriate cells, the Shiga toxin A subunit inhibits protein synthesis and promotes apoptosis of tumor cells. The difference in MOA allows for activity in the refractory setting, where resistance to other treatments has emerged, and may also allow for combination therapy. Pre-clinical studies with immunomodulatory drugs (IMiDs), PI3K and Bcl-2 inhibitors that are used in treatment of NHL have shown promising results when combined with MT-3724. MT-3724 is a promising novel agent in the treatment of NHL and other CD20 positive hematological malignancies. Data around the internalization kinetics, enzymatic activity, and combination with other agents will be presented. Citation Format: Garrett L. Robinson, Sangeetha Rajagopalan, Brigitte Brieschke, Jennifer Erdman, Jane Neill, Rodney E. Flores-Lefranc, Julia Foree, William Null, Jensing Liu, Jack P. Higgins, Erin K. Willert. MT-3724, an engineered toxin body targeting CD20 for non-Hodgkin9s lymphoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1483.
Risk and Protective Factors for Depressive Symptoms Among Indigenous Older Adults: Intimate Partner Violence (IPV) and Social Support

ABSTRACTResearch on depression and intimate partner violence (IPV) experienced by Indigenous older adults is virtually nonexistent. Given the associations between IPV and depression and their disproportionately high rates among Indigenous peoples in a context of historical oppression, the purpose of this inquiry is to examine how IPV and social support are associated with depressive symptoms for Indigenous older adults. We expand the knowledge base on IPV in later life, which primarily focuses on female samples, by including older men. We predicted: (a) IPV will be positively associated with depressive symptoms and (b) levels of social support will be negatively associated with depressive symptoms. Hierarchical regression analyses of data from a sample of Indigenous older adults (N = 233) in the Upper Midwest indicated that physical aggression (but not psychological aggression, sexual coercion, injury, or negotiation) was positively associated with depressive symptoms, whereas social support was negativel...
Pooled Analysis of the Effects of Conjugated Estrogens/Bazedoxifene on Vasomotor Symptoms in the Selective Estrogens, Menopause, and Response to Therapy Trials

Abstract Objectives: Conjugated estrogens/bazedoxifene (CE/BZA) reduced menopause-related hot flashes (HFs) in the Selective estrogens, Menopause, And Response to Therapy (SMART) trials. This post hoc pooled analysis of SMART-1 and -2 further characterized effects of CE/BZA on HFs in the overall population and patient subgroups. Methods: Data from two randomized, double-blind, placebo- and active-controlled, phase 3 studies were pooled for nonhysterectomized postmenopausal women with moderate/severe HFs given CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, or placebo for 12 weeks. HF frequency and severity were assessed by daily diary. Results: The pooled analysis included 403 participants. At 12 weeks, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg significantly (all p < 0.001) decreased moderate/severe HF frequency versus placebo (−7.9, −8.2, −4.1), reduced adjusted average daily HF severity score versus placebo (−1.0, −1.3, −0.3), increased the percentage of women who had a ≥50% (81.2%,87.1%, 50.6%) and ≥...
Asymptomatic Migration of a Kirschner Wire from the Proximal Aspect of the Humerus to the Thoracic Cavity: A Case Report.

Case: A 78-year-old man presented with an open fracture of the proximal aspect of the humerus and an axillary artery laceration; the fracture was treated provisionally with Kirschner wires (K-wires). Forty-five days postoperatively, he presented with pin prominence at the lateral aspect of the arm, and was incidentally noted to have migration of a separate K-wire to the left lung. He underwent successful thoracotomy and lung wedge resection for wire removal. Conclusion: K-wires used in the fixation of fractures of the proximal aspect of the humerus may migrate into the thoracic cavity. No modification of this technique, including the use of threaded, terminally bent, or external pins that are visibly secured, eliminates the potential for devastating complications.
Design and testing of acoustically-active therapeutic nanocapsule delivery vehicles for ultrasound-targeted chemotherapy

We propose that by utilizing acoustically-active delivery vehicles (AADVs), which combine the acoustic activity of an ultrasound contrast agent (UCA) with the high payload and extravasation ability of nanoparticles, we can overcome limitations of current chemotherapy delivery methodologies. AADV were formed by conjugating nanocapsules to the shell of biotinylated UCAs. Ultrasound parameters were optimized with a 2.25 MHz focused transducer using a flow phantom to achieve both acoustic radiation force and microbubble destruction. R3230 cells cultured on a cover slip were exposed to the AADV and sonicated with the focused transducer. Fluorescence microscopy verified binding of nanocapsules to ultrasound contrast agents to form AADVs, and increased delivery of nanocapsules to cells within the focus of the transducer (relative to nanocapsule delivery without ultrasound). An order-of-magnitude increase in particles were delivered to cells exposed to ultrasound compared to unexposed cells.
Athapaskan Classifiers, Person, and Deference

When we view the verb classifier prefixes from the perspective of comparative subject (actor)2properties, and from the perspective of discourse structure, we see the interplay of Person and Anaphora on two levels of historical grammar. Comparative subject (actor) properties, indefiniteness and depersonalization, figure importantly in the constitution of the morphological set known in the Athapaskan literature as "classifiers." In particular, we find that depersonalization via pluralization of first person subject (actor) plays a major role in the regularization of this paradigm. Additionally, deictic elements employed in discourse coreference and deference behaviors intersect the Proto-Athapaskan person system at first person plural.
Müller Cell–Microglia Cross Talk Drives Neuroinflammation in Diabetic Retinopathy

Diabetic retinopathy (DR) is the most common complication of diabetes and a leading cause of vision loss worldwide (1). Unfortunately, there are no treatments targeting early stages of the disease prior to the onset of sight-threatening vascular defects such as macular edema or neovascularization. A better understanding of the etiology of DR is needed to identify therapeutic targets to halt early disease progression. To this end, numerous studies demonstrated that a low-grade inflammation occurs in retinas of diabetic animal models and suggest that inflammation contributes a role in DR progression. Various mechanisms leading to retinal inflammation in DR have been described, with the majority of studies implicating retinal Muller glial cells and microglia as the initiators of retinal inflammation (for review, see ref. 2). However, seldom does a study make a strong connection between these two cell types. In this issue of Diabetes , Portillo et al. (3) describe a mechanism in which retinal inflammation in diabetic mice is dependent upon expression of the cluster of differentiation gene 40 (CD40) receptor by Muller cells (Fig. 1). The study suggests that CD40 activation induces Muller cells to release ATP, leading to activation of P2X7 purinergic receptors on retinal microglia and their subsequent expression of inflammatory cytokines. Importantly, the requirement of Muller cell–specific CD40 expression to recapitulate the appearance of acellular capillaries in diabetic retinas also suggests that inflammation is necessary for the loss of vascular cells associated with DR pathology. Figure 1 Proposed …
Neutrophil Microparticles Deliver Active Myeloperoxidase to Injured Mucosa To Inhibit Epithelial Wound Healing.

Neutrophil (PMN) infiltration of the intestinal mucosa often leads to severe epithelial injury; however, how this process occurs is unclear. This article describes a novel mechanism whereby membrane-derived microparticles released by tissue infiltrating PMNs (PMN-MPs) serve as shuttles to protect and deliver active mediators to locally modulate cellular function during inflammation. Specifically, myeloperoxidase (MPO), which is abundantly expressed in PMN azurophilic granules and is used for microbial killing, was found to be mobilized to the PMN surface and subsequently released in association with PMN-MPs upon PMN activation and binding to intestinal epithelial cells (IECs). The enzymatic activity of PMN-MP–associated MPO was enhanced compared with soluble protein, leading to potent inhibition of wound closure following PMN-MP binding to IECs. Importantly, localized microinjection of PMN-MPs into wounded colonic mucosa was sufficient to impair epithelial wound healing in vivo. PMN-MP/MPO–dependent inhibition of IEC wound healing was due to impaired IEC migration and proliferation, resulting from impeded actin dynamics, cell spreading, and cell cycle arrest. Thus, our findings provide new insight into mechanisms governing PMN-induced tissue injury and implicate PMN-MPs and MPO as important regulators of cellular function.
Cohesin mediates Esco2-dependent transcriptional regulation in a zebrafish regenerating fin model of Roberts Syndrome.

Robert syndrome (RBS) and Cornelia de Lange syndrome (CdLS) are human developmental disorders characterized by craniofacial deformities, limb malformation, and mental retardation. These birth defects are collectively termed cohesinopathies as both arise from mutations in cohesion genes. CdLS arises due to autosomal dominant mutations or haploinsufficiencies in cohesin subunits ( SMC1A , SMC3 and RAD21 ) or cohesin auxiliary factors ( NIPBL and HDAC8 ) that result in transcriptional dysregulation of developmental programs. RBS arises due to autosomal recessive mutations in cohesin auxiliary factor ESCO2 , the gene that encodes an N-acetyltransferase which targets the SMC3 subunit of the cohesin complex. The mechanism that underlies RBS, however, remains unknown. A popular model states that RBS arises due to mitotic failure and loss of progenitor stem cells through apoptosis. Previous findings in the zebrafish regenerating fin, however, suggest that Esco2 - knockdown results in transcription dysregulation, independent of apoptosis, similar to that observed in CdLS patients. Previously, we used the clinically relevant CX43 to demonstrate a transcriptional role for Esco2. CX43 is a gap junction gene conserved among all vertebrates that is required for direct cell-cell communication between adjacent cells such that cx43 mutations result in Oculodentodigital dysplasia. Here we show that morpholino-mediated knockdown of smc3 reduces cx43 expression and perturbs zebrafish bone and tissue regeneration similar to those previously reported for esco2 knockdown. Importantly, Smc3-dependent bone and tissue regeneration defects are rescued by transgenic Cx43 overexpression, providing evidence that Smc3 directly contributes to RBS-type phenotypes (i.e. skeletal defects) in the regenerating fin model. Moreover, chromatin immunoprecipitation (ChIP) assays reveal that Smc3 binds to a discrete region of the cx43 promoter, suggesting that Esco2 exerts transcriptional regulation of cx43 through modification of Smc3 bound to the cx43 promoter. These findings have the potential to unify RBS and CdLS as transcription-based mechanisms.
Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: analysis of the national cancer data base.

Background: To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation (CRT) in the National Cancer Data Base (NCDB). Methods: The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV−. Univariate analysis (UVA) was performed using the χ 2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. Results: A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n=498, 46.8%) and HPV− (n=565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR: 0.60, 95% CI: 0.38–0.96; P=0.034). However, for women, HPV infection did not significantly influence survival (HR: 1.47, 95% CI: 0.96–2.25; P=0.074). Conclusions: To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.
Extending the POWER Architecture with Transprecision Co-Processors

Approximate Computing is an emerging computer architecture paradigm which allows to trade off machine accuracy for energy efficiency. Initial studies have shown that Approximate Computing can significantly reduce the energy consumption of computer systems by introducing certain means of imprecision into the microarchitecture of the processor and memory units. However, it is not clear how quickly concepts that affect the precision will be adopted by enterprise class systems, because they need to deliver a high level of reliability, availability and serviceability (RAS). In this paper we propose to extend the traditional POWER architecture with closely coupled, transprecision co-processors. Transprecision co-processors use a re-configurable data path that can be optimized according to the precision requirements of the running algorithm. We show how FPGAs can be used to implement transprecision co-processors and conclude that CAPI is providing an innovative solution for coupling transprecision accelerators tightly to a CPU.
Evaluation of low-oligosaccharide, low-phytate whole soybeans and soybean meal in canine foods

Eight mature dogs (19.3 +/- 0.1 kg) were used in an experiment to compare the effects of feeding soybeans containing low concentrations of oligosaccharides and phytate on nutrient availability in complete foods fed to dogs. All foods were formulated to be isonitrogenous and contained low-oligosaccharide, low-phytate soybean meal (LLM); conventional soybean meal (SBM); low-oligosaccharide, low-phytate whole soybeans (LLB); or conventional whole soybeans (WSB) as the protein source. Daily DMI averaged 287 +/- 4 g/d. Fecal outputs were greatest for LLB and WSB, averaging 48.2 g DM/d. Small intestinal DM digestibility ranged from 80.9% (LLM) to 74.0% (LLB) but was unaffected by treatment. Large intestinal DM digestibility did not differ among treatments (P = 0.652). Total-tract DM digestibility was higher (P = 0.020) for LLM (87.0%) than for SBM (84.8%). No difference in total-tract DM digestibility was observed for the two WSB foods (average = 83.3%; P = 0.286). Nitrogen retention did not differ among foods containing LLM and SBM (1.2 g of N/d; P = 0.486) or LLB and WSB (0.9 g of N/d; P = 0.225). Small intestinal N digestibility did not differ among LLM- and SBM-containing foods (80.6%; P = 0.190) or LLB and WSB (69.3%; P = 0.640). Total-tract N digestibility did not differ among foods containing LLM and SBM (83.5%; P = 0.627) or LLB and WSB (76.8%; P = 0.968). Tryptophan digestibility was higher for SBM than for LLM (P = 0.039). Histidine and tryptophan digestibilities were higher in WSB compared with LLB (P = 0.049 and P < 0.001, respectively). No differences in nonessential AA digestibility were observed when comparing soy-based foods. The results of this study demonstrate that LLM, SBM, LLB, and WSB can be effective sources of protein for canine foods and have a high digestibility. Differences in small intestinal digestibility of tryptophan and histidine may require consideration when formulating diets using low-oligosaccharide, low-phytate soybeans or meal.
SOME ALMOST SURE CONVERGENCE PROPERTIES OF WEIGHTED SUMS OF MARTINGALE DIFFERENCE SEQUENCES

Publisher Summary This chapter discusses some convergence results for weighted sums that need not be martingales because of the double array structure of the weights. Lyapunov functions are commonly used in the stability analysis of differential difference equations. Lyapunov functions are also used to dominate the martingale difference sequences; conversely, Martingale theory is used to analyze the recursive relations for the Lyapunov-type function. They are important to stability theory and control theory. They are scalar functions that can be used to prove the stability of equilibrium of an ODE.
Bladder Cancer and Squamous Metaplasia in Spinal Cord Injury Patients

The influence of long-term indwelling urethral catheterization was studied by random bladder and urethral biopsies in 62 spinal cord injury patients. Six patients (10 per cent) had diffuse squamous cell bladder carcinoma, 4 of whom had no tumor visible endoscopically. Five of the patients with cancer were among 25 patients (20 per cent) managed with an indwelling urethral catheter for more than 10 years (average 21 years, range 15 to 30 years). The other cancer patient had been free of the catheter for 27 years after suprapubic cystotomy for 4 years. Gross and microscopic hematuria was associated with cancer. Squamous metaplasia of the bladder was significantly greater in patients who had been catheterized for more than 10 years (80 per cent), compared to those catheterized for less than 10 years (42 per cent) and patients without catheters (20 per cent). Urethral squamous metaplasia increased slightly in long-term catheterization patients. Urinary infection was universal and did not distinguish patients with inflammation, metaplasia or cancer. Therefore, the duration of indwelling catheterization seems to be the major factor in squamous changes in these patients.
Introducing information literacy into a marketing budget class assignment: A case study

AbstractThis case study describes collaboration between an instructor and business librarian to create an additional information literacy session for a marketing class all undergraduate business ma...
ERASMUS: Efficient remote attestation via self-measurement for unattended settings

Remote attestation (RA) is a popular means of detecting malware in embedded and IoT devices. RA is usually realized as a protocol via which a trusted verifier measures software integrity of an untrusted remote device called prover. All prior RA techniques require on-demand operation. We identify two drawbacks of this approach in the context of unattended devices: First, it fails to detect mobile malware that enters and leaves the prover between successive RA instances. Second, it requires the prover to engage in a potentially expensive computation, which can negatively impact safety-critical or real-time devices. To this end, we introduce the concept of self-measurement whereby a prover periodically (and securely) measures and records its own software state. A verifier then collects and verifies these measurements. We demonstrate a concrete technique called ERASMUS, justify its features, and evaluate its performance. We show that ERASMUS is well-suited for safety-critical applications. We also define a new metric — Quality of Attestation (QoA).
Specialized Commercial Courts in Iraq

As Iraq seeks to reconstruct its infrastructure after decades of war and neglect, foreign investment and foreign technologies are critical for the completion of projects to a standard deserving of the Iraqi people. Over the last 10 years, Iraq’s economic development has been hindered by myriad political, structural and security issues that have prevented the necessary reforms from being adopted. The branches of Government typically tasked with governance - the executive and legislature - have largely failed to effectively create a legal environment conducive to foreign investment and trade. However, a unique phenomenon has occurred in Iraq over the last four years where the judiciary has taken the lead in advocating legal reform, utilising the court system to improve Iraq’s business climate.
Stakeholder Engagement in Curricular Design: Addressing Current and Emergent Community Needs

As part of a curricular needs assessment for a nonprofit concentration within a Master of Public Administration program, this research compares the Nonprofit Academic Centers Council (NACC) curricular guidelines with stakeholder perceptions of current and emerging knowledge required for success in the nonprofit workforce. Although respondents’ top-ranked NACC domains indicate a strong preference for operations-based education, which is consistent with prior research, there is an additional preference for skills that allow nonprofit leaders to function strategically and competitively in the greater nonprofit landscape. Of the ranked NACC domains, leadership and fund development were consistently prioritized as current and emerging areas of knowledge; however, respondents placed an additional emphasis on information technology and marketing and communication as future skill needs. Finally, this research provides the faculty of a nonprofit concentration necessary information to retool, and perhaps redevelop, some of the nonprofit curriculum to meet stakeholder needs and educational standards. Subscrieb to JNEL
Development of a Short-Term to Long-Term Supervised Spiking Neural Network Processor

We report a realization of a mixed-signal, supervised spiking neural network (SNN) architecture utilizing short-term plasticity in synaptic resistive random access memory (RRAM). First, the development of a phenomenological RRAM SPICE model is discussed based on the previously reported device data. Then, the design of the neuroprocessor’s architectural components are described. To achieve learning using the synaptic RRAM devices, a novel method of backpropagation in hardware SNNs is presented using the proposed gated bidirectional amplifier circuit. A method to perform quantized weight transfer between the short-term memory (STM) and long-term memory (LTM) is also proposed, allowing transient associated memories to be stored and used repeatedly. The neuroprocessor is able to associate input digits with class labels, transfer learned associations to a long-term register array, then recall all digits when presented again. The low operational power of 13.7 mW makes this system ideal for future integration onto embedded systems with limited available energy. Finally, the neuroprocessor’s tolerance to input noise and internal device failure was measured to be 14% and 15%, respectively. We believe that this work provides significant insight into the development of hardware SNNs in addition to providing a framework to achieve more complex STM to LTM interactions in the future.
A clinical classification system for grading platinum hypersensitivity reactions.

Abstract Objectives Current grading systems for platinum hypersensitivities (pHSR) rely on subjective features rather than objective clinical signs leading to inconsistencies in grading. To standardize classification of pHSR, a clinical grading system was developed at our institution. We report the clinical outcomes our classification system and evaluate its correlation with the classification systems currently published and used in practice. Methods This was a retrospective review of patients with pHSR from 2011 to 2017. Demographics, chemotherapeutic histories (CT), and details of their initial HSR were collected. Mild reactions were defined as local skin manifestations only. Moderate-low reactions included widespread skin, respiratory or GI findings. Moderate-standard reactions were defined as transient cardiovascular compromise (CVC), hypoxia or neurologic changes whereas sustained changes (>10 min) were used to define severe reaction. Fischer Exact Tests (p Results 87 patients were identified with most having ovarian cancer (n = 55, 63.2%), receiving carboplatin (n = 62, 71.3%), and on second-line CT (n = 34, 42.5%). Chest pain was associated with transient CVC (OR 10.0, 95% CI 1.148–87.133) while nausea/vomiting (OR 8.420, 95% CI 1.263–55.275) was associated with transient hypoxia albeit less closely than transient hypotension (OR 17.010, 95% CI 2.026–142.825). Only presyncope/syncope remained associated with sustained CVC (OR 38.0, 95% CI 2.815–512.912) on logistic regression. The classification system was most strongly correlated with the NCCN grading system (ρ 0.761, p Conclusions This classification system offers an objective means of grading pHSR severity and correlates with currently-used grading systems.
Engaging Equity Pedagogies in Computer Science Learning Environments

In this position paper, we advocate for the use of equity-focused teaching and learning as an essential practice within computer science classrooms. We provide an overview of the theoretical underpinnings of various equity pedagogies (Banks & Banks, 1995), such as culturally relevant pedagogy (Ladson-Billings, 1995, 2006) and share how they have been utilized in CS classrooms. First, we provide a brief history of CS education and issues of equity within public schools in the United States. In sharing our definition of equity, along with our rationale for how and why these strategies can be taken up in computer science (CS) learning environments, we demonstrate how researchers and educators can shift the focus from access and achievement to social justice. After explaining the differences between the relevant theoretical frameworks, we provide practical examples from research of how both practitioners and researchers might use and/or examine equity-focused teaching practices. Resources for further learning are also included.
Sacudidas privadas compartidas: poesía de la pandemia

Presentacion de poemas sobre el tema de la pandemia del COVID-19 en la America Latina. Presentation of poems on the COVID-19 pandemic in Latin America
Cortical Mechanisms of Saccadic Suppression

Saccades are a ubiquitous and crucial component of our visual system, allowing for the efficient deployment of the fovea and its accompanying neural resources. Initiation of a saccade is known to cause saccadic suppression, a temporary reduction in visual sensitivity1,2 and visual cortical firing rates3-6. While saccadic suppression has been well characterized at the level of perception and single neurons, relatively little is known about the visual cortical networks governing this phenomenon. Here we examine the effects of saccadic suppression on distinct neural subpopulations within area V4. We find cortical layer- and cell type-specific differences in the magnitude and timing of peri-saccadic modulation. Neurons in the input layer show changes in firing rate and inter-neuronal correlations prior to saccade onset, suggesting that this layer receives information about impending saccades. Putative inhibitory interneurons in the input layer elevate their firing rate during saccades and may play a role in suppressing the activity of other cortical subpopulations. A computational model of this circuit recapitulates our empirical observations and demonstrates that an input layer-targeting pathway could initiate saccadic suppression by enhancing local inhibitory activity. Together, our results provide a mechanistic understanding of how eye movement signaling interacts with cortical circuitry to enforce visual stability.
The empowerment plan: Enhancing the safety plan with a CBS approach to repertoire expansion

Abstract Safety planning is an essential tool for helping those considering suicide stay safe, and it is best practice for assisting veterans who are in crisis. Further elaboration on this tool, as well as integration of empirically supported therapeutic interventions, may lead to greater engagement and possibility for change. Stanley and Brown's safety plan (2012) has been implemented in the Veterans Health Administration Medical Centers (VA) and is considered the standard of care for suicidal behavior in veterans, a population with a well-documented vulnerability to suicide. The unique characteristics of a CBS-informed safety plan (supplemented with components of Relational Frame Theory), or Empowerment Plan, is contrasted with Stanley and Brown's approach. Increasing specificity with RFT provides the clinician with sets of targeted interventions to empower the patient, providing the CBS therapist with skills to enhance safety planning. The goal is to identify multiple ways to amplify meaning and associated action into awareness, thus, connecting the veteran with reasons and motivation to live. The key elements of a transdiagnostic, process-focused approach to safety planning are delineated. A description for creating a CBS-informed single-session safety plan is provided.
Alcohol, cannabis, and brain development

Abstract Alcohol and cannabis are two of the most common licit and illicit drugs used among pregnant women. Prenatal alcohol exposure can lead to a wide variety of physical and behavioral deficits known as fetal alcohol spectrum disorders; alcohol is a known teratogen and can have neurotoxic effects on the developing brain. However, the effects of prenatal cannabis exposure are not well understood. There is some evidence that the psychoactive constituents of cannabis, such as delta-9-tetrahydrocannabinol (THC), may be neurotoxic as well, although past evidence has been inconsistent and does not reflect the high potency of THC in cannabis products today. Moreover, even less is known about the combined effects of prenatal alcohol and cannabis exposure, although half of all women who report drinking alcohol during pregnancy also report consuming cannabis. Although the developing brain is incredibly plastic, making it more vulnerable to teratogenic effects, this plasticity also makes postnatal interventions possible.
Perceived Social Support and Heart Rate Variability: An Integrative Review.

The purpose of this integrative review is to explore and synthesize literature about the relationship between perceived social support and cardiac vagal modulation, measured by heart rate variabili...
Common Methodology for Efficient Airspace Operations

Topics include: a) Developing a common methodology to model and avoid disturbances affecting airspace. b) Integrated contrails and emission models to a national level airspace simulation. c) Developed capability to visualize, evaluate technology and alternate operational concepts and provide inputs for policy-analysis tools to reduce the impact of aviation on the environment. d) Collaborating with Volpe Research Center, NOAA and DLR to leverage expertise and tools in aircraft emissions and weather/climate modeling. Airspace operations is a trade-off balancing safety, capacity, efficiency and environmental considerations. Ideal flight: Unimpeded wind optimal route with optimal climb and descent. Operations degraded due to reduction in airport and airspace capacity caused by inefficient procedures and disturbances.
Similarity of the outer capsid protein VP4 of the Gottfried strain of porcine rotavirus to that of asymptomatic human rotavirus strains.

Abstract Genomic segment 4 of the porcine Gottfried strain (serotype 4) of porcine rotavirus, which encodes the outer capsid protein VP4, was sequences, and its deduced amino acid sequence was analyzed. Amino acid homology of the porcine rotavirus VP4 to the corresponding protein of asymptomatic or symptomatic human rotaviruses representing serotypes 1 to 4 ranged from 87.1 to 88.1% for asymptomatic strains and from 77.5 to 77.8% for symptomatic strains. Amino acid homology of the Gottfried strain to simian rhesus rotavirus, simian SA11 virus, bovine Nebraska calf diarrhea virus, and porcine OSU strains ranged from 71.5 to 74.3%. Antigenic similarities of VP4 epitopes between the Gottfried strain and human rotaviruses were detected by a plaque reduction neutralization test with hyperimmune antisera produced against the Gottfried strain or a Gottfried (10 genes) x human DS-1 rotavirus (VP7 gene) reassortant which exhibited serotype 2 neutralization specificity. In addition, a panel of six anti-VP4 monoclonal antibodies capable of neutralizing human rotaviruses belonging to serotype 1, 3, or 4 was able to neutralize the Gottfried strain. These observations suggest that the VP4 outer capsid protein of the Gottfried rotavirus is more closely related to human rotaviruses than to animal rotaviruses.
Human Immunodeficiency Virus Type 2 (HIV-2)

Human immunodeficiency virus type 2 (HIV-2) is the second human immunodeficiency virus in the class of human retro-viruses; it constitutes the closest known virus related to the prototype AIDS virus, HIV-1. HIV-2 is endemic in West Africa and is rare in Asia. Nevertheless, the virus demonstrates unique biologic features that inform our understanding of HIV viruses in general.
A Non-test for Ambiguity*

In a recent article in this journal, Roberts (1984) suggests a semantic method for distinguishing ambiguity and generality, a method which is intended to avoid the problems that others such as Zwicky and Sadock (1975), Hintikka (1973), and McCawley (1980) have found in making such a decision. Roberts claims that his test derives its validity from the observation that an ambiguous expression has a disjunction of meanings, whereas a general expression has but one meaning (which might be disjunctive).1 According to Roberts, a term 'is ambiguous rather than general if and only if its meaning is <p in some contexts and ¥ in other contexts' (299-300). His test involves placing a questionable example in a context and asking whether the meaning of the term is <p in that context, whether it is * in that context, or whether it is (<p or ¥) in that context. If a context can be found such that the meaning of the term is <p, and if a context can be found such that the meanng of the term is ¥, then the ambiguity of the expression has been demonstrated. If, however,
Games of inquiry for collaborative concept structuring

Google's project to digitize five of the world's greatest libraries will dramatically extend their search engine reach in the future. Current search-engine philosophy, which asserts that ”any search starts with a question to be answered,” will need to be advanced in terms of Peirce's philosophy: ”Any inquiry begins by creating an hypothesis to be tested, or with abduction.” As conceptual structures researchers prepare to meet access challenges in the world of large Internet knowledge stores, they have a solid foundation in Peirce's theorized stages of inquiry: abduction, deduction, and induction. To indicate how conceptual structures tools must augment collaborative, Internet-based inquiry, we imagine a future scenario in the context of a user-centered testbed, where Peirce scholars apply Peirce's pragmatic theory in their complex manuscript reconstruction work. We suggest that games of inquiry can be developed to formalize user collaboration and technology needs, for improved specification of tool requirements in the testbed context.
Extracellular matrix (mesoglea) of Hydra vulgaris: I. Isolation and characterization☆

Hydrozoans such as Hydra vulgaris, as with all classes of Cnidaria, are characterized by having their body wall organized as an epithelial bilayer with an intervening acellular layer termed the mesoglea. The present study was undertaken to determine what extracellular matrix (ECM) components are associated with Hydra mesoglea. Using polyclonal antibodies generated from vertebrate ECM molecules, initial light and electron microscopic immunocytochemical studies indicated the presence of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin immunoreactive components in Hydra mesoglea. These immunocytochemical observations were in part supported by biochemical analyses of isolated Hydra mesoglea which indicated the presence of fibronectin and laminin based on Western blot analysis. Amino acid analysis of total mesoglea and some of its isolated components confirmed the presence of collagen molecules in mesoglea. Additional studies indicated the presence of (1) a gelatin binding protein in Hydra which was immunoreactive with antibodies raised to human plasma fibronectin and (2) a noncollagen fragment extracted from mesoglea which was immunoreactive to antibodies raised to the NC1 domain (α1 subunit) of bovine glomerular basement membrane type IV collagen. These observations indicate that Hydra mesoglea is evolutionarily a primitive basement membrane that has retained some properties of interstitial ECM.
Heterogeneity of the conserved ribosomal ribonucleic acid sequences of Bacillus subtilis.

Doi, Roy H. (University of California, Davis), and Richard T. Igarashi. Heterogeneity of the conserved ribosomal ribonucleic acid sequences of Bacillus subtilis . J. Bacteriol. 92: 88–96. 1966.—Hybrid formation was demonstrated between Bacillus subtilis ribosomal ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) from various bacterial species. The high degree of complementarity between B. subtilis ribosomal RNA and the DNA from B. cereus and B. stearothermophilus suggested a method to test whether the same RNA sequences were hybridizing with the DNA from these two species. Saturation studies with 16 S and 23 S RNA preparations from B. subtilis showed that a definite number of complementary sites was present in each DNA. Base composition analyses of the RNA in the hybrid demonstrated that ribosomal RNA sequences were involved. Hybrid competition studies revealed that B. stearothermophilus ribosomal RNA could compete totally against B. subtilis ribosomal RNA for B. stearothermophilus DNA, although it could compete only partially against the B. subtilis ribosomal RNA hybridizing with B. cereus DNA . These observations were made independently with both 16 S and 23 S ribosomal RNA preparations. These results revealed that different nucleotide sequences of B. subtilis ribosomal RNA were hybridizing with the DNA from B. cereus and B. stearothermophilus . Two possible interpretations of these results are: (i) different nucleotide sequences from a homogeneous ribosomal RNA population are hybridizing with heterologous DNA preparations, and (ii) ribosomal RNA cistrons are heterogeneous.
Grandmothers Raising Grandchildren: Results of an Intervention to Improve Health Outcomes

Purpose: To examine the impact of an intervention to improve the health of grandmothers raising grandchildren in parent-absent homes. Design: A longitudinal, pretest-posttest design. Methods: The sample was composed of 529 female caregivers with a mean age of 56.7 years (range 38–83) who were predominantly low-income African Americans. Data were collected prior to the intervention and again at 12 months when the intervention was complete. The intervention involved home visitation by registered nurses and social workers, as well as other support services. The Short Form-36 was used to assess physical and mental health, using eight multi-item scales. Results: A comparison of pre- and posttest mean scores on the SF-36 indicated significantly (p < .003) improved mean scores for vitality, physical effects on role functioning, emotional effects on role functioning, and mental health. No significant differences were found for other attributes. Conclusions: These preliminary findings suggest that grandmothers raising grandchildren may benefit from a home-based intervention designed to improve health attributes. Implications for nursing practice, policy, and research are presented. Clinical Relevance: The health of grandmother caregivers is critical to their ability to parent grandchildren successfully. Nurses practicing in a variety of settings are in a unique position to identify and address the health challenges of grandmothers who are raising grandchildren.
Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β– and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very lo...
Who is the Fairest of Them All? Choosing a Leader at Deronde International

Alain Deronde, the CEO of a French personal care company has to choose a successor to head global product development from a diverse set of candidates with different backgrounds, strengths, and weaknesses. The candidates include Elise Bernier, Vice President of Marketing for Skin Care Products , Antoine Lambert, General Manager of Coeur Tendre (an ex-entrepreneur whose company Deronde had bought), Yang Jianguo, Country Manager of Deronde International's Chinese subsidiary, and Yves Saurac, Vice President of Product Development for Developed Markets.
Blood, Sweat and Tears

In this issue of The American Journal of Bioethics (AJOB), we explore the controversy over a set of industry sponsored clinical trials for an artificial blood, PolyHeme. There are multiple dimensio...
Multi-Dimensional Ratings of Adult Occupations

Occupations have traditionally been classified on the basis of sex-type, job description, or educational level and potential income. In this study the question of whether occupations can be grouped on the basis of particular social attributes is addressed. Subjects (N = 118) rated each of 58 occupations on selected social attributes, specifically, prestige, power, complexity associated with an occupation and strength and gentleness required for an occupation, as well as sex-type. A cluster analysis procedure was used to group occupations on the basis of the ratings. Nine clusters resulted, five essentially male, three female, and one neutral. All were further distinguished on the basis of the social attributes. The exploratory nature of this study is noted and the relevance of these findings for research in children's stereotyping of occupations and in the development of occupational models is discussed.
Simulation of overexpanded low-density nozzle plume flow

The direct simulation Monte Carlo method was applied to the analysis of low-density nitrogen plumes exhausting from a small converging-diverging nozzle into finite ambient pressures. Two cases were considered that simulated actual test conditions in a vacuum facility. The numerical simulations readily captured the complicated flow structure of the overexpanded plumes adjusting to the finite ambient pressures, including Mach disks and barrel-shaped shocks. The numerical simulations compared well to experimental data of Rothe.
What makes a revolution

The article reviews the book "Field Notes From a Catastrophe: Man, Nature, and Climate Change," by Elizabeth Kolbert.
Web-based Collaborative Care for Type 2 Diabetes: a Pilot Randomized Trial

OBJECTIVE —To test Web-based care management of glycemic control using a shared electronic medical record with patients who have type 2 diabetes. RESEARCH DESIGN AND METHODS —We conducted a trial of 83 adults with type 2 diabetes randomized to receive usual care plus Web-based care management or usual care alone between August 2002 and May 2004. All patients had GHb ≥7.0%, had Web access from home, and could use a computer with English language–based programs. Intervention patients received 12 months of Web-based care management. The Web-based program included patient access to electronic medical records, secure e-mail with providers, feedback on blood glucose readings, an educational Web site, and an interactive online diary for entering information about exercise, diet, and medication. The primary outcome was change in GHb. RESULTS —GHb levels declined by 0.7% (95% CI 0.2−1.3) on average among intervention patients compared with usual-care patients. Systolic blood pressure, diastolic blood pressure, total cholesterol levels, and use of in-person health care services did not differ between the two groups. CONCLUSIONS —Care management delivered through secure patient Web communications improved glycemic control in type 2 diabetes.