cssi/SciSciGPT-SciSciNet huggingface dataset:
PCFIRE: Towards provable preventative Control-Flow Integrity enforcement for realistic embedded software

Control-Flow Integrity (CFI) is an important safety property of software, particularly in embedded and safety-critical systems, where CFI violations have led to patient deaths and can render cars remotely controllable by attackers. Previous techniques for CFI may reduce the robustness of embedded and safety-critical systems, as they handle CFI violations by stopping programs. In this work, we present PCFIRE, a preventative approach to CFI that prevents the root-causes of CFI violations to allow recovery, and enables programmers to specify robust recovery actions by providing CFI via source-code safety-checks. PCFIRE's CFI can be formally proved automatically, and supports realistic features of embedded software such as hardware and I/O access. We showcase PCFIRE by providing, and automatically proving, CFI for: benchmark programs, text utilities containing I/O, and embedded programs with sensor inputs and hardware outputs on the Raspberry Pi single-board computer.
The Cost of Brain Surgery: Awake vs Asleep Craniotomy for Perirolandic Region Tumors.

Background Cost effectiveness has become an important factor in the health care system, requiring surgeons to improve efficacy of procedures while reducing costs. An awake craniotomy (AC) with direct cortical stimulation (DCS) presents one method to resect eloquent region tumors; however, some authors assert that this procedure is an expensive alternative to surgery under general anesthesia (GA) with neuromonitoring. Objective To evaluate the cost effectiveness and clinical outcomes between AC and GA patients. Methods Retrospective analysis of a cohort of 17 patients with perirolandic gliomas who underwent an AC with DCS were case-control matched with 23 patients with perirolandic gliomas who underwent surgery under GA with neuromonitoring (ie, motor-evoked potentials, somatosensory-evoked potentials, phase reversal). Inpatient costs, quality-adjusted life years (QALY), extent of resection, and neurological outcome were compared between the groups. Results Total inpatient expense per patient was $34 804 in the AC group and $46 798 in the GA group ( P = .046). QALY score for the AC group was 0.97 and 0.47 for the GA group ( P = .041). The incremental cost per QALY for the AC group was $82 720 less than the GA group. Postoperative Karnofsky performance status was 91.8 in the AC group and 81.3 in the GA group (P = .047). Length of hospitalization was 4.12 days in the AC group and 7.61 days in the GA group ( P = .049). Conclusion The total inpatient costs for awake craniotomies were lower than surgery under GA. This study suggests better cost effectiveness and neurological outcome with awake craniotomies for perirolandic gliomas.
Suppression of Red Blood Cell Autofluorescence for Immunocytochemistry on Fixed Embryonic Mouse Tissue

Autofluorescence is a problem that interferes with immunofluorescent staining and complicates data analysis. Throughout the mouse embryo, red blood cells naturally fluoresce across multiple wavelengths, spanning the emission and excitation spectra of many commonly used fluorescent reporters, including antibodies, dyes, stains, probes, and transgenic proteins, making it difficult to distinguish assay fluorescence from endogenous fluorescence. Several tissue treatment methods have been developed to bypass this issue with varying degrees of success. Sudan Black B dye has been commonly used to quench autofluorescence, but can also introduce background fluorescence. Here we present a protocol for an alternative called TrueBlack Lipofuscin Autofluorescence Quencher. The protocol described in this unit demonstrates how TrueBlack efficiently quenches red blood cell autofluorescence across red and green wavelengths in fixed embryonic tissue without interfering with immunofluorescent signal intensity or introducing background staining. We also identify optimal incubation, concentration, and multiple usage conditions for routine immunofluorescence microscopy. © 2017 by John Wiley & Sons, Inc. Keywords: autofluorescence; red blood cell; fluorescent microscopy; embryonic tissue; immunocytochemistry
The Resilience to Emergencies and Disasters Index: Applying big data to benchmark and validate neighborhood resilience capacity

Abstract Resilience planning and emergency management require policymakers and agency leaders to make difficult decisions regarding which at-risk populations should be given priority in the allocation of limited resources. Our work focuses on benchmarking neighborhood resilience by developing a unified, multi-factor index of local and regional resilience capacity: the Resilience to Emergencies and Disasters Index (REDI). The strength of the REDI methodology is the integration of measures of physical, natural, and social systems – operationalized through the collection and analysis of large-scale, heterogeneous, and high resolution urban data – to classify and rank the relative resilience capacity embedded in localized urban systems. Feature selection methodologies are discussed to justify the selection of included indicator variables. Hurricane Sandy is used to validate the REDI scores by measuring the recovery periods for neighborhoods directly impacted by the storm. Using over 12,000,000 records for New York City’s 311 service request system, we develop a proxy for neighborhood activity, both pre- and post-event. Hurricane Sandy had a significant and immediate impact on neighborhoods classified as least resilient based on the calculated REDI scores, while the most resilient neighborhoods were shown to better withstand disruption to normal activity patterns and more quickly recover to pre-event functional capacity.
Direct intertectal inputs are an integral component of the bilateral sensorimotor circuit for behavior in Xenopus tadpoles.

The developing optic tectum of Xenopus tadpoles represents a unique circuit in which laterally positioned eyes provide sensory input to a circuit that is transiently monocular, but which will be bi...
Adoption Issues in Perspective: An Introduction to the Special Issue

The process and dynamics of adoption have changed considerably in the last 50 years, assisted by both social change and new knowledge of human development. The current status of 3 important aspects of adoption is reviewed: 1) the general effects of relinquishment and adoption, 2) the effects of secrecy in adoption, and 3) the need to add information on the dynamics of adoption to the training of therapists. The articles contained in this special adoption issue of the Journal of Social Distress and the Homeless are summarized and are placed in context of the 3 aspects reviewed.
Communication Boards: Design and Construction:

If one were to identify the most beneficial tangible apparatus for nonverbal individuals, undoubtedly, the communication board would rate highly. For those who are not familiar with the use of such...
Immediate and short-term effects of kinesiotaping on muscular activity, mobility, strength and pain after rotator cuff surgery: a crossover clinical trial

Kinesiotape (KT) is widely used in musculoskeletal rehabilitation as an adjuvant to treatment, but minimal evidence supports its use. The aim of this study is to determine the immediate and short-term effects of shoulder KT on muscular activity, mobility, strength and pain after rotator cuff surgery. Thirty-nine subjects who underwent shoulder rotator cuff surgery were tested 6 and 12 weeks post-surgery, without tape, with KT and with a sham tape (ST). KT and ST were applied in a randomized order. For each condition, the muscular activity of the upper trapezius, three parts of the deltoid and the infraspinatus were measured during shoulder flexion, and range of motion (ROM) and pain intensity were assessed. At 12 weeks, the isometric strength at 90° of shoulder flexion, related muscular activity and pain intensity were also measured. Subjects maintained the last tape that was applied for three days and recorded the pain intensity at waking up and during the day. Modifications in muscle activity were observed with KT and with ST. Major changes in terms of decreased recruitment of the upper trapezius were observed with KT (P < 0.001). KT and ST also increased flexion ROM at 6 weeks (P = 0.004), but the differences with the no tape condition were insufficient to be clinically important. No other differences between conditions were found. Shoulder taping has the potential to decrease over-activity of the upper trapezius, but no clinical benefits of KT on ROM, strength or pain were noted in a population of subjects who underwent rotator cuff surgery. The study was retrospectively registered on ClinicalTrials.gov PRS ( NCT03379636 ) on 21st December 2017.
Preventing early-onset group B streptococcal sepsis: is there a role for rescreening near term?

Objective: The Centers for Disease Control and Prevention 2010 guidelines recommend group B streptococcus (GBS) screening at 35–37-week gestation to identify women with positive cultures who should...
Encephalopathy in neonates with subgaleal hemorrhage is a key predictor of outcome.

Background Subgaleal hemorrhage (SGH) is reported to be associated with severe hemodynamic instability, coagulopathy, and even mortality. The importance of the presence or absence of neonatal encephalopathy in predicting SGH outcomes has not been explored. The aim of this study was to determine the relationship of clinical encephalopathy to short-term outcomes in neonates with SGH. Methods Neonates ≥35 weeks gestation, diagnosed radiologically with SGH between 2010 and 2017, were included. Cases were divided into encephalopathic and non-encephalopathic. Demographic, clinical, and outcome data were compared between groups. Results Of 54,048 live births, 56 had SGH, of them 13 (23%) had encephalopathy. When compared to the non-encephalopathic neonates, encephalopathic neonates had lower Apgar scores, lower hemoglobin, lower platelet count, longer neonatal intensive care unit stay, two (15%) deaths, and four (31%) required blood transfusion. No non-encephalopathic infant with SGH died or required blood transfusion. Notably, on magnetic resonance imaging (MRI), a majority of subgaleal collections had either no or minimal blood products. Conclusions In the absence of encephalopathy, SGH is not associated with adverse short-term outcome. Neurological assessment is likely to identify infants at higher risk for adverse outcome. The absence of MRI signal consistent with blood in subgaleal collection warrants further research.
The Effectiveness of Psychoeducation and Brief Treatments in the Aftermath of Sexual Assault

Recent estimates indicate that roughly 20% of US adult women and 1.7% of men report being raped during their lifetime and an estimated 1.6% of women report being raped in the previous 12 months (Breiding et al., Surveillance Summaries, 63:1–18, 2014b). Sexual assault victimization is associated with higher rates of revictimization, interpersonal difficulties, and social stigma. Survivors of sexual assault are also at an increased risk of abusing alcohol and drugs, even among those who did not abuse substances prior to the assault (Kilpatrick et al., Journal of Consulting and Clinical Psychology 65:834, 1997a). As such, there is an impetus to develop brief and evidence-based interventions that target the unique constellation of challenges faced by sexual assault victims. The aim of this chapter is to examine the available support for brief treatments and psychoeducational interventions in the aftermath of trauma and discuss limitations and future directions for research.
Post-Intentional Phenomenology as Ethical and Transformative Inquiry and Practice: Through Intercultural Phenomenological Dialogue

This study is a conceptual dialogue aimed at attaining insight into reading and developing postintentional phenomenology as intercultural philosophical inquiry. This conversation commences with the...
I/O Acceleration via Multi-Tiered Data Buffering and Prefetching

Modern High-Performance Computing (HPC) systems are adding extra layers to the memory and storage hierarchy, named deep memory and storage hierarchy (DMSH), to increase I/O performance. New hardware technologies, such as NVMe and SSD, have been introduced in burst buffer installations to reduce the pressure for external storage and boost the burstiness of modern I/O systems. The DMSH has demonstrated its strength and potential in practice. However, each layer of DMSH is an independent heterogeneous system and data movement among more layers is significantly more complex even without considering heterogeneity. How to efficiently utilize the DMSH is a subject of research facing the HPC community. Further, accessing data with a high-throughput and low-latency is more imperative than ever. Data prefetching is a well-known technique for hiding read latency by requesting data before it is needed to move it from a high-latency medium (e.g., disk) to a low-latency one (e.g., main memory). However, existing solutions do not consider the new deep memory and storage hierarchy and also suffer from under-utilization of prefetching resources and unnecessary evictions. Additionally, existing approaches implement a client-pull model where understanding the application’s I/O behavior drives prefetching decisions. Moving towards exascale, where machines run multiple applications concurrently by accessing files in a workflow, a more data-centric approach resolves challenges such as cache pollution and redundancy. In this paper, we present the design and implementation of Hermes: a new, heterogeneous-aware, multi-tiered, dynamic, and distributed I/O buffering system. Hermes enables, manages, supervises, and, in some sense, extends I/O buffering to fully integrate into the DMSH. We introduce three novel data placement policies to efficiently utilize all layers and we present three novel techniques to perform memory, metadata, and communication management in hierarchical buffering systems. Additionally, we demonstrate the benefits of a truly hierarchical data prefetcher that adopts a server-push approach to data prefetching. Our evaluation shows that, in addition to automatic data movement through the hierarchy, Hermes can significantly accelerate I/O and outperforms by more than 2x state-of-the-art buffering platforms. Lastly, results show 10%–35% performance gains over existing prefetchers and over 50% when compared to systems with no prefetching.
Periaqueductal Gray and Rostromedial Tegmental Inhibitory Afferents to VTA Have Distinct Synaptic Plasticity and Opiate Sensitivity

Summary The ventral tegmental area (VTA) is a major target of addictive drugs and receives multiple GABAergic projections originating outside the VTA. We describe differences in synaptic plasticity and behavior when optogenetically driving two opiate-sensitive GABAergic inputs to the VTA, the rostromedial tegmental nucleus (RMTg), and the periaqueductal gray (PAG). Activation of GABAergic RMTg terminals in the VTA in vivo is aversive, and low-frequency stimulation induces long-term depression in vitro. Low-frequency stimulation of PAG afferents in vitro unexpectedly causes long-term potentiation. Opioid receptor activation profoundly depresses PAG and RMTg inhibitory synapses but prevents synaptic plasticity only at PAG synapses. Activation of the GABAergic PAG terminals in the VTA promotes immobility, and optogenetically-driven immobility is blocked by morphine. Our data reveal the PAG as a source of highly opioid-sensitive GABAergic afferents and support the idea that different GABAergic pathways to the VTA control distinct behaviors.
How Grey’s Anatomy Fooled Me into Thinking I Had Cancer

It’s often hard to distinguish between fact and opinion, especially in today’s age of media. This becomes a controversial topic once the media disperses information that could potentially be harmful to the public, particularly involving medicine. In this essay, a patient case is used as motivation to understand the complex relationship between medical misinformation in the media and empathy. Following is a discussion of how misinformation and empathy work with the human mind, and how medical dramas use them to their advantage. Then, Grey’s Anatomy is used as a case study to see how the show implements empathy and misinformation. Finally, an analysis of the positives and negatives of the medical drama is presented along with suggestions of how to improve medical dramas – particularly looking at possible outcomes for positive change in this medium of communication. keywords: empathy, medical misinformation, Grey’s Anatomy, health communication, medical drama
OP0043 RENAL TUBULAR COMPLEMENT C9 DEPOSITION IS ASSOCIATED WITH RENAL TUBULAR DAMAGE AND FIBROSIS IN LUPUS NEPHRITIS

Background: Tubulointerstitial damage in lupus nephritis (LN) is a strong predictor of progression to chronic kidney disease and end stage renal disease (ESRD). While prior studies showed complement activation mediates glomerular injury (1), the role of complement in renal tubular damage has not been evaluated. Objectives: To investigate the association between complement activation and tubulointerstitial fibrosis. Specifically, to study the role of tubular complement C9 deposition as a marker of tubular damage and fibrosis in LN. Methods: LN biopsies stored in the pathology department between July 2014 to July 2016 were evaluated. Chromogenic immunohistochemistry was performed on formalin-fixed, paraffin-embedded, 4-µm human renal biopsy sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197) as a marker of the terminal complement activation. C3 glomerulopathy was used as a positive control, and normal kidney from resected tumor served as a negative control. Tubular basement membrane C9 staining intensity were analyzed on a semi-quantitative scale from 0 to 3 by a renal pathologist. The degree of Interstitial fibrosis/tubular atrophy was categorized as low (0–10%), medium (11–20%), or high (≥21%). Clinical parameters were assessed at the time of biopsy and 6 months post biopsy. Results: Renal biopsies from 30 LN were studied, 23 (77%) of which had proliferative LN (Table). There were 24 (80%) women, mean (SD) age 33 (12) years. Positive tubular C9 staining (C9+) was observed in 7 (23%) biopsies. There was no significant difference in eGFR at renal biopsy between the two groups. At the time of renal biopsy, C9+ patients had significantly higher proteinuria, compared to C9- patients: median (IQR) 6.2g (3.3-13.1) vs. 2.4g (1.3-4.6), p Conclusion: Tubular C9 deposition is significantly associated with proteinuria, interstitial fibrosis and increased chronicity which predict progression to ESRD and mortality. Complement activation in the tubules may be linked to proteinuria and more studies are needed to elucidate its mechanism in tubulointerstitial damage in LN. References: [1]Wang S, Wu M, Chiriboga L, Zeck B, Belmont HM. Membrane attack complex (mac) deposition in lupus nephritis is associated with hypertension and poor clinical response to treatment. Semin Arthritis Rheum. 2018;48(2):256-62. Disclosure of Interests: None declared
Analytical Chemistry Online? Lessons Learned from Transitioning a Project Lab Online Due to COVID-19

While project laboratories have become a staple in analytical chemistry courses, Coronavirus 2019 (COVID-19) has forced many universities to adopt an online instruction model, which raises challenges in creating quality content that matches the learning objectives of the course. Here we describe the transition of an inquiry-based project lab from a data-collection-focused experience into a statistical-analysis-driven one using a previously collected data set. Student opinions on the project were collected using a postproject feedback form, and instructors were surveyed for their observations. The major focus of this communication is a discussion of the common successes and challenges found in the staff and student feedback. Although we underestimated the personal struggles of individual students and the communication issues that occurred, overall our reimagination of the project was successful, especially in the adaptation of the course material and the resources developed for student success. For future iterations of this course, all of the lessons learned will be applied to both remote and in-person instruction where possible.
A calibrated sensitivity analysis for matched observational studies with application to the effect of second‐hand smoke exposure on blood lead levels in children

We conducted a matched observational study to investigate the causal relationship between second‐hand smoke and blood lead levels in children. Our first analysis that assumes no unmeasured confounding suggests evidence of a detrimental effect of second‐hand smoke. However, unmeasured confounding is a concern in our study as in other observational studies of second‐hand smoke's effects. A sensitivity analysis asks how sensitive the conclusion is to a hypothesized unmeasured confounder U. For example, in our study, one potential unmeasured confounder is whether the child attends a public or private school. A commonly used sensitivity analysis for matched observational studies adopts a worst‐case perspective, which assumes that, in each matched set, the unmeasured confounder is allocated to make the bias worst: in a matched pair, the child with higher blood lead level always attends public school and the other private school. This worst‐case allocation of U does not correspond to any realistic distribution of U in the population and is difficult to compare with observed covariates. We proposed a new sensitivity analysis method that addresses these concerns. We apply the new method to our study and find that, to explain away the association between second‐hand smoke exposure and blood lead levels as non‐causal, the unmeasured confounder would have to be a bigger confounder than any measured confounder.
Stoichiometry of Rtt109 complexes with Vps75 and histones H3-H4.

Histone acetylation is one of many posttranslational modifications that affect nucleosome accessibility. Vps75 is a histone chaperone that stimulates Rtt109 acetyltransferase activity toward histones H3-H4 in yeast. In this study, we use sedimentation velocity and light scattering to characterize various Vps75–Rtt109 complexes, both with and without H3-H4. These complexes were previously ill-defined because of protein multivalency and oligomerization. We determine both relative and absolute stoichiometry and define the most pertinent and homogeneous complexes. We show that the Vps75 dimer contains two unequal binding sites for Rtt109, with the weaker binding site being dispensable for H3-H4 acetylation. We further show that the Vps75–Rtt109–(H3-H4) complex is in equilibrium between a 2:1:1 species and a 4:2:2 species. Using a dimerization mutant of H3, we show that this equilibrium is mediated by the four-helix bundle between the two copies of H3. We optimize the purity, yield, and homogeneity of Vps75–Rtt109 complexes and determine optimal conditions for solubility when H3-H4 is added. Our comprehensive biochemical and biophysical approach ultimately defines the large-scale preparation of Vps75–Rtt109–(H3-H4) complexes with precise stoichiometry. This is an essential prerequisite for ongoing high-resolution structural and functional analysis of this important multi-subunit complex.
Professionalizing Practice Through Research

Research engagement supports professionalism in language teaching in multiple ways. It leads to improved outcomes but also serves to empower teachers. Because many people associate research with something done by university-based academics, it is helpful to consider what the term actually implies with respect to processes and outcomes. As a process it involves structured inquiry, a connection to practice, and a commitment to dissemination, with each of these phases allowing for a range of types. Overcoming barriers to research requires strategies for unpacking this process in a way that allows for scaffolding and support. Strategies for conceptualizing and planning, conducting and reflecting, and disseminating and receiving feedback are discussed along with various resources that teachers can turn to for support.
Female rats consume and prefer oxycodone more than males in a chronic two-bottle oral voluntary choice paradigm

ABSTRACT The increased abuse of opioids - such as oxycodone - poses major challenges for health and socioeconomic systems. Human prescription opioid abuse is marked by continuous, voluntary, oral intake, and sex differences. Therefore the field would benefit from a preclinical in-depth characterization of sex differences in a chronic oral voluntary, free choice, and continuous access paradigm. Here we show in an oral oxycodone continuous access two-bottle choice paradigm sex-dependent voluntary drug intake, dependence, and motivation to take the drug. Adult female and male Long-Evans rats were given unlimited, continuous home cage access to two bottles containing water (Control) or one bottle of water and one bottle of oxycodone dissolved in water (Experimental). Most experimental rats voluntarily drank oxycodone (∼10 mg/kg/day) and escalated their intake over 22 weeks. Females self-administered twice as much oxycodone as males, leading to greater blood levels of oxycodone, and engaged in more gnawing behavior. Precipitated withdrawal revealed high levels of dependence in both sexes. Reflecting motivation to drink oxycodone, ascending concentration of citric acid suppressed the intake of oxycodone (Experimental) and the intake of water (Control); however Experimental rats returned to pre-citric acid preference levels whereas Controls rats did not. Thus, female rats consumed and preferred oxycodone more than males in this chronic two-bottle oral choice paradigm. Both sexes displayed many features of human oxycodone abuse, and behavioral pre-screening predicted parameters of intake and withdrawal. This model provides an additional paradigm for understanding mechanisms that mediate long-term voluntary drug use and for exploring potential treatment options. HIGHLIGHTS Adult rats offered continuous choice of oral oxycodone vs. water preferred oxycodone Rats self-titrated oxycodone, yet females preferred and escalated more than males Both sexes were motivated to drink oxycodone, as shown by a citric acid aversion test Both sexes became dependent on oxycodone, as shown by precipitated withdrawal Behavioral prescreening predicted later aspects of oxycodone intake and dependence
Review of commercially available genomic technologies in cattle

Genetic testing can be a key component of a beef cattle management program. Available tests can help inform parentage, selection for simple traits like coat color or polled, management of genetic defects in breeding populations, and estimating the genetic merit of individual animals for economically relevant traits. Increasingly, comprehensive genotyping arrays that assess tens of thousands of genetic markers are being used to inform selection in cattle populations.
Is addiction a brain disease? A plea for agnosticism and heterogeneity.

Rationale Although increasingly subject to criticism, the brain disease model of addiction (BDMA) remains dominant within addiction science. Yet few advocates or critics of the BDMA have provided an account of what a brain disease is. The aim of this review is to conceptually clarify what it would mean for the BDMA to be true, rather than to argue decisively for or against it. Objectives Conceptual clarification of the BDMA requires consideration of possible models of disease and their relationship to the BDMA. A barrier to such consideration is belief that the BDMA is necessary to combatting addiction stigma. To address this barrier, I begin with discussion of what we know about the effects of the brain disease label on addiction stigma, and why labelling effects should have no bearing on the validity of the BDMA. I then distinguish strong, minimal, network, and mismatch models of disease, and I argue that the BDMA aligns with a strong disease model. This means that underlying brain pathology is hypothesized to be the cause of the personal-level observable signs and experienced symptoms characteristic of addiction. Evaluation of the BDMA therefore requires analysis of the concepts of brain dysfunction and causation, and their application to addiction science. Results Brain dysfunction cannot be analyzed merely as brain changes or brain differences; nor can it be inferred merely from the presence of personal-level signs and symptoms. It is necessary to have an account of normal brain function by which to measure it. The theoretical and empirical challenges to developing such an account are not insurmountable, but they are substantial. Although there exist competing analyses of causation, there is a relatively standard method used to establish it within experimental science: intervention. Using this method, the causal significance of brain states, such as, e.g., extensive gray matter loss and/or neuroadapations in the mesocorticolimbic dopamine system, is not yet fully demonstrated. Further studies are necessary to determine their effect compared with other possible variables, such as, e.g., alternative reinforcers. Conclusions Conceptual clarification and preliminary empirical assessment of the BDMA recommends agnosticism about its validity and an openness to heterogeneity; in some cases addiction may be a brain disease, in others not. Either way, addiction stigma can be combatted by fighting moralism about drugs and moralistic drug policies directly, as opposed to resting hopes on the brain disease label.
New Perspectives on Language and Thought

This chapter discusses the question of whether, how, where, and to what extent language plays a causally fundamental role in creating categories of thought, and in organizing and channeling thought that is already mentally present. In general, both logic and currently available evidence suggest a disclamatory view of strongest proposals (e.g., Benjamin Whorf, 1956) according to which particulars of certain human languages are important progenitors of thought, such that elements of perception or conception would be permanently altered by learning one or another language. However, several credible lines of experimental and developmental evidence suggest significant influence of linguistic representation during on-line processing in many cognitive and perceptual domains: Insofar as languages differ in the short-term processing demands that they pose to listeners, interpretational outcomes and styles, including characteristic ambiguity resolution, may look quite different cross-
Advances in the understanding and treatment of multiple sclerosis: Boston, Massachusetts, USA, 28–29 October 1992

Basic and applied research on multiple sclerosis (MS) has become increasingly focused on the development and testing of new therapeutic agents for this devastating disease. After a generation or more of exposing patients to non-specific immunoregulatory and other agents that have been, at best, of minimum benefit and significant potential or actual toxicity, attention has turned to attempts to identify treatment modalities that might be used in a more specific, effective and safe fashion. This trend has not been lost on the emerging biotechnology industry, which tends to view MS as both a disease to be explored on its own and as a disease whose solution may also open doors into other chronic diseases of purported autoimmune etiology, such as rheumatoid arthritis, type I diabetes, and others. These trends toward an increasing biotechnological approach to MS, coupled with an academic and industrial focus on the disease, were the clear motivations behind a recent two-day conference entitled "Advances in the Understanding and Treatment of Multiple Sclerosis" held in Boston and sponsored by a commercial meeting planner, International Business Communications USA Conferences, Inc.
Neuronal Nitric Oxide Synthase Is Necessary for Elimination of Giardia lamblia Infections in Mice

NO produced by inducible NO synthase (NOS2) is important for the control of numerous infections. In vitro, NO inhibits replication and differentiation of the intestinal protozoan parasite Giardia lamblia. However, the role of NO against this parasite has not been tested in vivo. IL-6-deficient mice fail to control Giardia infections, and these mice have reduced levels of NOS2 mRNA in the small intestine after infection compared with wild-type mice. However, NOS2 gene-targeted mice and wild-type mice treated with the NOS2 inhibitor N-iminoethyl-L-lysine eliminated parasites as well as control mice. In contrast, neuronal NOS (NOS1)-deficient mice and wild-type mice treated with the nonspecific NOS inhibitor NG-nitro-L-arginine methyl ester and the NOS1-specific inhibitor 7-nitroindazole all had delayed parasite clearance. Finally, Giardia infection increased gastrointestinal motility in wild-type mice, but not in SCID mice. Furthermore, treatment of wild-type mice with NG-nitro-L-arginine methyl ester or loperamide prevented both the increased motility and the elimination of parasites. Together, these data show that NOS1, but not NOS2, is necessary for clearance of Giardia infection. They also suggest that increased gastrointestinal motility contributes to elimination of the parasite and may also contribute to parasite-induced diarrhea. Importantly, this is the first example of NOS1 being involved in the elimination of an infection.
Light-induced cross-linking of DNA in the presence of a furocoumarin (psoralen). Studies with phage lambda, Escherichia coli, and mouse leukemia cells.

Abstract 1. 1. Interstrand cross-links are formed in native DNA by irradiation with 360-nm light in the presence of 4,5′,8-trimethylpsoralen. The yield of this product is similar in phage λ DNA in vitro and Escherichia coli DNA in intact bacterial cells. 2. 2. DNA of mammalian cells in tissue culture is also reversibly renaturable after psoralen-light treatment, indicating that psoralen cross-links may contribute to the skin photosensitizing action observed for this class of compounds. 3. 3. We suggest that the cross-linking reaction may result from reaction of an excited psoralen molecule with the pyrimidine bases in opposite strands of the DNA duplex.
Transportability across studies: A formal approach

We provide a formal definition of the notion of “transportability,” or “external validity,” which we view as a license to transfer causal information learned in experimental studies to a different environment, in which only observational studies can be conducted. We introduce a formal representation called “selection diagrams” for expressing knowledge about differences and commonalities between populations of interest and, using this representation, we derive procedures for deciding whether causal effects in the target environment can be inferred from experimental findings in a different environment. When the answer is affirmative, the procedures identify the set of experimental and observational studies that need be conducted to license the transport. We further demonstrate how transportability analysis can guide the transfer of knowledge among non-experimental studies to minimize re-measurement cost and improve prediction power. We further provide a causally principled definition of “surrogate endpoint” and show that the theory of transportability can assist the identification of valid surrogates in a complex network of cause-effect relationships.
A Model of Vertical Differentiation for Online Retailing

The Internet has changed the nature of doing business as well as the nature of competition in many industries. The number of online transactions has seen a steady increase as more consumers turn to online retailing (e-tailing) for a wide range of product choices and shopping convenience. Yet, despite the availability of online comparison shopping sites and the ease of finding alternative e-tailers for a given product, the persistent and substantial price dispersion has not been fully understood. In this paper, we view the online purchase of a product as a bundle of utilities consisting of the satisfaction with the product itself, the service received from the purchase experience, as well as the assurance and trust associated with the e-tailer's brand recognition. E-tailers, accordingly, can differentiate themselves in the service, brand recognition, and price dimensions. We extend the two dimensional competitive model to three dimensions in which e-tailers sequentially decide on a recognition level, then a service quality, and finally compete on price. We solve the model analytically and obtain closed-form equilibrium solutions. By explicitly incorporating differentiation costs, we show the existence of previously unknown equilibria, among which an asymmetric Max-Max equilibrium that is frequently observed in practice. In addition, the e-tailer's optimal competitive strategy is determined by the structure of the differentiation costs.
Parallel in situ detection of connected components in adaptive mesh refinement data

Adaptive Mesh Refinement (AMR) represents a significant advance for scientific simulation codes, greatly reducing memory and compute requirements by dynamically varying simulation resolution over space and time. As simulation codes transition to AMR, existing analysis algorithms must also make this transition. One such algorithm, connected component detection, is of vital importance in many simulation and analysis contexts, with some simulation codes even relying on parallel, in situ connected component detection for correctness. Yet, current detection algorithms designed for uniform meshes are not applicable to hierarchical, non-uniform AMR, and to the best of our knowledge, AMR connected component detection has not been explored in the literature. Therefore, in this paper, we formally define the general problem of connected component detection for AMR, and present a general solution. Beyond solving the general detection problem, achieving viable in situ detection performance is even more challenging. The core issue is the conflict between the communication-intensive nature of connected component detection (in general, and especially for AMR data) and the requirement that in situ processes incur minimal performance impact on the co-located simulation. We address this challenge by presenting the first connected component detection methodology for structured AMR that is applicable in a parallel, in situ context. Our key strategy is the incorporation of an multi-phase AMR-aware communication pattern that synchronizes connectivity information across the AMR hierarchy. In addition, we distil our methodology to a generic framework within the Combo AMR infrastructure, making connected component detection services available for many existing applications. We demonstrate our method's efficacy by showing its ability to detect ice calving events in real time within the real-world BISICLES ice sheet modelling code. Results show up to a 6.8x speedup of our algorithm over the existing specialized BISICLES algorithm. We also show scalability results for our method up to 4,096 cores using a parallel Combo-based benchmark.
Gene Transfer by Transduction in the Marine Environment

To determine the potential for bacteriophage-mediated gene transfer in the marine environment, we established transduction systems by using marine phage host isolates. Plasmid pQSR50, which contains transposon Tn5 and encodes kanamycin and streptomycin resistance, was used in plasmid transduction assays. Both marine bacterial isolates and concentrated natural bacterial communities were used as recipients in transduction studies. Transductants were detected by a gene probe complementary to the neomycin phosphotransferase (nptII) gene in Tn5. The transduction frequencies ranged from 1.33 x 10(-7) to 5.13 x 10(-9) transductants/PFU in studies performed with the bacterial isolates. With the mixed bacterial communities, putative transductants were detected in two of the six experiments performed. These putative transductants were confirmed and separated from indigenous antibiotic-resistant bacteria by colony hybridization probed with the nptII probe and by PCR amplification performed with two sets of primers specific for pQSR50. The frequencies of plasmid transduction in the mixed bacterial communities ranged from 1.58 x 10(-8) to 3.7 x 10(-8) transductants/PFU. Estimates of the transduction rate obtained by using a numerical model suggested that up to 1.3 x 10(14) transduction events per year could occur in the Tampa Bay Estuary. The results of this study suggest that transduction could be an important mechanism for horizontal gene transfer in the marine environment.
Alternative EFT developments and the quality of life: A theoretical analysis

Abstract This article develops a theoretical position for studying the impacts of different electronic funds transfer (EFT) arrangements upon the quality of life. A conception of quality of life is defined which emphasizes the relative power of participants in a social setting as well as their personal resources and sentiments. A ‘design space’ for characterizing alternative EFT designs is then set up, and the social textures of different EFT arrangements are examined.
Structural Optimization of a Linearly Elastic Structure using the Homogenization Method

We shall describe a brief review of the structural optimization of a linearly elastic structure, and we shall present a new method to solve the sizing, shape, and layout (topology) problems based on the theory of homogenization. Many numerical examples of the optimal design are also presented as well as a mathematical formulation of a relaxed design problem.
Discovering admissible heuristics by abstracting and optimizing: a transformational approach

We present an implemented model for discovering a class of state-space search heuristics. First, abstractions of a state-space problem are generated by dropping information from the problem definition. An optimal solution path for any such abstracted problem gives a lower bound on the true distance to the goal. This bound can be used as an admissible evaluation function for guiding the base-level search. Moreover, if the abstracted goal is unreachable from an abstracted state, the original state can safely be pruned. However, using exhaustive search to evaluate the abstracted problem is generally too slow. Therefore, optimization is used to speed up the computation of the lower bound (or solvability test), for example by factoring the abstracted problem into independent subproblems. We analyze the conditions under which the resulting heuristic is faster than brute force search. Our implementation, named ABSOLVER, has several general transformations for abstracting and simplifying state-space problems, including a novel method for problem factoring. ABSOLVER appears t o be the first mechanical generator of heuristics guaranteed to find optimal solution paths. We have used it to derive known and novel heuristics for various state space problems, including Rubik's Cube.
International Law and the Shrinking Space for Politics in Developing Countries

This article asks to what extent and by what processes should international legal norms be incorporated into domestic constitutions particularly in developing countries. It raises several concerns about the democratic legitimacy of many international legal norms and therefore about the wisdom of the developing countries incorporating international legal norms into domestic law without extensive political deliberation. The internationalization of constitutional interpretation rests on several problematic assumptions. First, proponents of internationalization of constitutional interpretation assume that several international norms, originally only human rights but now increasingly environmental norms, are universal and should be incorporated without specific democratic approval. Second, other international norms, delineated as customary international norms, are perceived to be formed by the consent of the world community of nations and are therefore obligatory.The importation of international norms by developing countries is especially problematic because they have so little input into international norms and institutions. Developing countries are receivers of international law, not makers of international law. Such norms may be of questionable legitimacy in these societies, and may be inappropriate policy choices in countries at a different stage of economic development than more developed western countries. My concern is that with globalization and the increased dominance of the western democracies in international law formation there has been a turn away from consent as the basis of international law making and towards Naturalism. Premature international legalism takes normative development and sensible trade-offs out of the realm of both international and domestic politics without the necessary political deliberation. Rights have costs both in financial resources and political resources that should be assessed along with competing claims.
Die Bürgerrechte V: Die Versammlungsfreiheit

Auch die offentliche Versammlung (assembly) ist an sich nichts anderes als eine bestimmte — und zwar besonders nachdruckliche — Technik der Meinungskundgebung. Die Veranstalter oder Einberufer als die Aktivisten in einer offentlichen Angelegenheit versprechen sich von der Massenunterstutzung ihrer Ziele durch die anonym bleibende Teilnehmer- und Zuhorerschaft eine starkere Wirkung ihrer eigenen Meinung — gleichgultig ob politischer, wirtschaftlicher, religioser oder kultureller Natur. Bei der kollektiven Meinungsauserung aber, wie sie eine Versammlung darstellt, bestehen gewisse Unterschiede, die sie von der blos individuellen Meinungsauserung abgrenzen: Sie erfordert ein bestimmtes Mas organisatorischer Vorbereitung — wie die Bereitstellung eines Versammlungslokals oder -platzes und dessen Ankundigung, der Leiter und Redner, moglicherweise auch eines internen Ordnungsdienstes. Diese technischen Vorbereitungsmasnahmen werden, falls keine organisierte Vereinigung — etwa eine politische Partei — dahintersteht, von den Veranstaltern oder Einberufern vorgenommen, welche sich zu diesem Zweck als eine Art ad hoc- Vereinigung, wenn auch formlos konstituiert haben. Wahrend also die Meinungskundgebung bei einer Vereinigung auf eine gewisse Dauer berechnet ist, beschrankt sie sich bei der Versammlung auf eine einmalige Wirkung.
Synaptically Released Glutamate Activates Extrasynaptic NMDA Receptors on Cells in the Ganglion Cell Layer of Rat Retina

NMDA and AMPA receptors (NMDARs and AMPARs) are colocalized at most excitatory synapses in the CNS. Consequently, both receptor types are activated by a single quantum of transmitter and contribute to miniature and evoked EPSCs. However, in amphibian retina, miniature EPSCs in ganglion cell layer neurons are mediated solely by AMPARs, although both NMDARs and AMPARs are activated during evoked EPSCs. One explanation for this discrepancy is that NMDARs are located outside of the synaptic cleft and are activated only when extrasynaptic glutamate levels increase during coincident release from multiple synapses. Alternatively, NMDARs may be segregated at synapses that either are not spontaneously active or yield miniature EPSCs that are too small to detect. In this study, we examined excitatory, glutamatergic synaptic inputs to neurons in the ganglion cell layer of acute slices of rat retina. EPSCs, elicited by electrically stimulating presynaptic bipolar cells, exhibited both NMDAR- and AMPAR-mediated components. However, spontaneous EPSCs exhibited only an AMPAR-mediated component. The effects of low-affinity, competitive receptor antagonists indicated that NMDARs encounter less glutamate than AMPARs during an evoked synaptic response. Reducing glutamate uptake or changing the probability of release preferentially affected the NMDAR component in evoked EPSCs; reducing uptake revealed an NMDAR component in spontaneous EPSCs. These results indicate that NMDARs are located extrasynaptically and that glutamate transporters prevent NMDAR activation by a transmitter released from a single vesicle and limit their activation during evoked responses.