cssi/SciSciGPT-SciSciNet huggingface dataset:
Physics and Causation

More than a century ago, Russell launched a forceful attack on causation, arguing not only that modern physics has no need for causal notions but also that our belief in causation is a relic of a pre-scientific view of the world. He thereby initiated a debate about the relations between physics and causation that remains very much alive today. While virtually everybody nowadays rejects Russell's causal eliminativism, many philosophers (although by no means all) have been convinced by Russell that the fundamental physical structure of our world doesn't contain causal relations. This raises the question of how to reconcile the central role of causal concepts in the special sciences and in common sense with the putative absence of causation in fundamental physics.
Antibody Responses and Functions in Defense against Viral Infection

Antibodies, also called immunoglobulins, are glycoproteins expressed by B cells that serve as the principal immune molecules preventing viral reinfection following a prior infection or vaccination. B cells use a unique set of genetic programs including recombination of variable gene segments and somatic hypermutation of variable genes to generate enormous diversity in the repertoires of combining sites that recognize foreign antigens. Stimulated B cells can differentiate into plasma cells, which secrete the antibodies as soluble immunoglobulins. Antibodies also use diverse constant regions that mediate varying functions by regulating interaction with the complement system and different types of antibody receptors on other immune cells. Antibodies inhibit virus infection by a multitude of mechanisms, including aggregation, blocking of attachment to cell receptors, fusion inhibition, and inhibition of virus uncoating. Some antibodies facilitate cellular cytoxicity by binding to virus-infected cells and activating cytolytic cells by engaging cell surface receptors.
CE-40 Long-term development of autoimmune disease in children with neonatal lupus and their unaffected siblings

Background Several studies have evaluated mortality and short term morbidity in neonatal lupus (NL), however there is minimal data on long term outcomes in children exposed to maternal anti-Ro antibodies in utero. A previous pilot study utilising the Research Registry for Neonatal Lupus (RRNL) raised concern regarding the development of autoimmune disease in childhood, however the numbers evaluated were small and the patients studied were young. This study was initiated to ascertain the current prevalence of autoimmune disease in NL children and their unaffected siblings, and to evaluate whether fetal or maternal factors associated with the development of future autoimmunity. Materials and methods A retrospective cohort of family members from the RRNL were contacted to evaluate for autoimmune disease. Follow-up questionnaires were completed which included 35 items describing symptoms and diagnoses associated with autoimmunity in 138 cardiac NL children, 74 cutaneous NL children, and 134 unaffected siblings. Medical records were obtained and evaluated from the patient’s physicians to confirm diagnoses. Maternal diagnosis of systemic lupus and/or Sjogren’s syndrome and fetal cardiac disease severity based on a previously described severity score were associated with postnatal autoimmune diseases using chi square and Mann-Whitney analyses. Results Seventeen (8.0%) of NL affected children developed an autoimmune disease at the time of follow up (mean age 11.6±9.0 years). These included 3 patients with SLE, 1 with JIA, 3 with thyroid disease, 5 with psoriasis, 1 with IBD, 1 with uveitis, 1 with UAS and 2 with type 1 DM. Six (4.5%) unaffected siblings developed an autoimmune disease (mean age 10.6±7.1 years), which included 1 with JIA, 1 with Sarcoidosis/ITP, 1 with Myasthenia Gravis/Celiac disease, 1 with psoriasis, 1 with UAS and 1?with type 1 DM,. There was a significant association of between having an autoimmune disease and having advanced heart block (11.0% vs. 4.2%, p = 0.03) and a trend towards an association with cardiac NL disease severity score (4.43±4.89 vs. 2.58±4.24, p = 0.06). Mother’s diagnosis of SLE or Sjogren’s did not associate with the children’s development of autoimmune disease (p = 0.828). Conclusions Fetuses that develop advanced congenital heart block as a manifestation of NL may be at greater risk for developing autoimmune diseases later in life. This could potentially relate to a genetic component that makes a Ro exposed fetus both more prone to inflammatory effects of passive immunity and predisposes to future autoimmunity, independent of the mother’s rheumatic disease status.
Transient Thermal Analysis of HTS DC Cables Cooled With Gaseous Helium Using a Volume Element Method

Gaseous helium is being considered as a cryogen for a variety of high-power density applications. It is capable of reaching operational temperature levels as low as 20 K. This paper presents a time efficient method of designing and modeling a high-temperature superconducting dc cable. The analysis is an extension of a previously presented mathematical model in which the volume element method was used to characterize the fluid flow and heat transfer by conduction, convection, and radiation through a flexible cable cryostat. A system of ordinary differential equations was formulated using the fundamental principles of thermodynamics. The computational domain consists of volume elements distributed in three dimensions to account for the spatial dependence of the model. The pressure drop of the gaseous helium was calculated based on the Darcy-Weisbach correlation. Additionally, the temperature distribution was solved numerically using adaptive time-stepping. The obtained solutions converge within a timescale on the order of seconds to minutes, and the steady state results along with a transient analysis is discussed.
Unidirectional waveguide grating antennas with uniform emission for optical phased arrays

We demonstrate millimeter-scale optical waveguide grating antennas with unidirectional emission for integrated optical phased arrays. Unidirectional emission eliminates the fundamental problem of blind spots in the element factor of a phased array caused by reflections of antenna radiation within the substrate. Over 90% directionality is demonstrated using a design consisting of two silicon nitride layers. Furthermore, the perturbation strength along the antenna is apodized to achieve uniform emission for the first time, to the best of our knowledge, on a millimeter scale. This allows for a high effective aperture and receiving efficiency. The emission profile of the measured 3 mm long antenna has a standard deviation of 8.65% of the mean. These antennas are state of the art and will allow for integrated optical phased arrays with blind-spot-free high transmission output power and high receiving efficiency for LIDAR and free-space communication systems.
Altered understory characteristics affect rodent spatial and foraging behaviors and reproduction patterns

Understanding how changes to habitat characteristics affect behaviors is necessary to integrate biodiversity goals with land management. Managed forests are a significant landscape component in the southern United States and provide opportunities for conservation alongside production of wood products. We investigated behavioral responses of rodents to differences in understory habitat characteristics from intercropping switchgrass (Panicum virgatum), a native biofuel feedstock, in intensively managed loblolly pine (Pinus taeda) stands. Previous research indicated that planting switchgrass increased rodent population abundance but reduced recruitment and community diversity. To understand potential mechanisms underlying our previous results, we measured behaviors of individual cotton rats (Sigmodon hispidus), a grassland specialist, to planted switchgrass. We hypothesized that female territory size, foraging activity, overlap with other adult females, and reproduction indices would differ among treatments (switchgrass monocrop, intercropped switchgrass, and control plots) due to variation in grass abundance and vertical vegetation cover. We conducted live-trapping, radio telemetry, and foraging activity surveys on cotton rats during summers of 2013–2015. We found no treatment effect on territory size, but foraging activity was 2 times higher in monocrop than control plots. We also found a positive relationship between female spatial overlap and percentage of grass in control plots and evidence for higher reproductive indices in control than monocrop plots. Our results suggest that cotton rats in monocrop plots exhibited unexpected behaviors, and monocrop plots may serve as population sinks with low rodent diversity. Overall, results from this replicated experiment suggested that intercropping provides adequate food and cover to maintain rodent populations and produce forest products.
Healthcare simulation for excellence in in-patient safety

In the US healthcare alone over 25,000 patients are sickened, injured or killed each day. The associated huge, tangible and intangible, costs are crippling burdens on all stakeholders. In the USA the national health budget is 1/6 of the GDP, of which 1/3 is estimated to be wasted. The United Nations World Health Organization is working toward making patient safety a Basic Human Right. A safe organization is a cost-effective quality organization wherein all stakeholders are trained to understand work processes and their role in them. Simulation-based program for training individuals and teams, which has a great potential to deliver high reliability care, is put forward by the authors. The simulations are structured around the Accident Trajectory that describes how incidents result from a combination of situational factors and system failures that predispose individuals to make mistakes (active errors). Details of this highly transferrable training methodology and the tools that help inculcate leadership, systems thinking, communication, situational awareness, teamwork, consensus-based problem solving and decision making, as well as adaptive responsiveness are presented. This is followed by proposed methods of assessment of resulting individual and team competencies. Also described are details of the formative assessment of the approach.
First Studies in Bioethics

This chapter discusses two landmark studies that introduce bioethical questions in the intensive care unit. A historical overview of level of care and self-determination of the patient is discussed.
Mathematical Modeling of Ebola Virus Dynamics as a Step towards Rational Vaccine Design

The greatest roadblock in vaccine design is the lack of a complete understanding of how the immune system works. Greater understanding can be achieved via mathematical models that formalize biological ideas and their ability to extract non-intuitive information from biological experiments. Rational vaccine design (RVD) aims to maximize the production of pathogen-specific memory cells following vaccination. First, the Herz model for viral dynamics was simulated using MATLAB to analyze the naive system’s response to Ebola – a deadly hemorrhagic virus. The model was initialized for the unvaccinated system using biologically based data on Ebola virus cultivation in Vero cell-cultures. Simulations revealed generally non-quantified specifics of Ebola infection such as the virus’ birth, natural death, and cellular infection rates. The second system, initialized with the rates above, modeled Ebola infection in a vaccinated individual using a modified Herz model with equations for memory T-cell formation and proliferation. T-cell populations were expanded under biologically mimicked rates and conditions. These results provide a quantified value for the number of memory T-cells necessary for vaccine efficacy in an individual; the specifications of what the vaccine must accomplish. Reversing the roles, these results may serve as RVD guidelines for biologically effective vaccines against the Ebola virus.
Pretreatment of Drinking Water to Control Organic Contaminants and Taste and Odor

This paper represents an evaluation of a laboratory study and related literature on pretreatment of drinking water for removal of organic contaminants and taste and odor. Pretreatment may include oxidation, aeration, biodegradation, or powdered activated carbon (PAC). The unit processes described are those used by the majority of water treatment plants in the USA, represented by the Philadelphia Suburban Water Company’s (PSWC) Neshaminy Plant.
Minimally Invasive Thoracolumbar Corpectomy and Stabilization for Unstable Burst Fractures Using Intraoperative Computed Tomography and Computer-Assisted Spinal Navigation.

Background Minimally invasive surgery using a mini-open lateral retropleural or retroperitoneal approach for corpectomy is a well-described procedure for treating unstable thoracolumbar burst fractures. Most surgeons have incorporated fluoroscopy for localization and determination of hardware placement accuracy; however, the utility of computer-assisted image-guided spinal navigation has not been well described. We report a series of mini-open lateral approach thoracolumbar corpectomy cases using either fluoroscopy or intraoperative computed tomography (iCT) with computer-assisted navigation and discuss the technical nuances and advantages of using iCT with navigation versus fluoroscopy. Methods A retrospective review and analysis was performed of the cases of 20 patients with thoracolumbar burst fractures surgically managed via mini-open lateral corpectomy with fluoroscopy (2013–2015) or iCT navigation (2015–2017). The surgical outcomes were evaluated by the estimated blood loss, operative time, hospital stay, and need for revision. The clinical outcomes were evaluated using the numerical rating scale pain score. Radiographic outcomes were assessed with follow-up CT scans. The results were statistically analyzed using the Wilcoxon-Mann-Whitney test. Results The mean follow-up period was 13.4 months for the fluoroscopy group and 14.7 months for the iCT group. No surgical complications developed and no revisions were required. No statistically significant differences were found between the groups in surgical or clinical outcomes. However, the radiation exposure to the surgeons was significantly less with the iCT group (P Conclusions The use of iCT with spinal navigation for mini-open lateral corpectomy for thoracolumbar burst fractures yields perioperative and clinical outcomes comparable to those using traditional fluoroscopy, with decreased radiation exposure to surgeons.
Profiles and Academic Trajectories of Cognitively Gifted Children with Autism Spectrum Disorder.

Gifted children with autism spectrum disorder (ASD) are often referred to as twice-exceptional, the term that highlights the co-occurrence of exceptional challenges and exceptional giftedness. This study performed secondary data analysis on samples of twice-exceptional children from the Pre-Elementary Education Longitudinal Study and the Special Education Elementary Longitudinal Study datasets. The results provide a descriptive profile of twice-exceptional (e.g. demographics, average academic performance, and services utilized), trajectory plots that indicate how academic performance changes over time, and multilevel analyses that model growth in academic outcomes using demographics, school services, and giftedness as predictors. Some of the key findings are that twice-exceptional students show not only higher initial levels of academic performance, but they improve over time relative to the non-gifted ASD counterparts and-with the exception of Letter Word Matching-even relative to the general population. Moreover, they benefit from mental health services disproportionately. Together, the results offer a deeper understanding of the twice-exceptional autistic population, their academic performance over time, and the services that they utilize.
Viremia copy-years and mortality among combination antiretroviral therapy-initiating HIV-positive individuals: how much viral load history is enough?

Objective Ongoing HIV replication while receiving combination antiretroviral therapy (cART) may reduce survival. Viremia copy-years (VCY) has shown improved mortality risk prediction over single time-point viral load measures. However, the timing of a patient's viral load history most associated with later mortality has not been studied. Here we determined the optimal duration and temporality of viral load history for predicting mortality. Design Survival analysis among HIV-positive men who initiated cART in the Multicenter AIDS Cohort Study (1995-2015). Methods VCY measures were derived from area-under-the-viral load-curve. The overall VCY based upon the complete post-cART viral load history was compared with 20 VCYs derived from viral loads assessed during different shorter time periods (the most recent 1-10 years and initial 1-10 years following cART initiation) for associations with mortality. Results Each 10-fold increase in VCYs based on the most recent 3-8 years was significantly associated with 23-26% decrease in survival times, a magnitude of effect greater than that of the most recent viral load (16%). These associations were independent of CD4 cell count and single time-point viral loads. In addition, the degree of pre-cART immunodeficiency did not affect the mortality prognostic value of VCY based on viral loads in the most recent 3 years. Conversely, the overall VCY and VCYs based on viral loads immediately following cART initiation were not independent predictors of mortality. Conclusion Among cART-treated men, VCY based upon viral loads in the recent 3 years (six viral loads) has a mortality prognostic value greater than that of the overall VCY and single time-point viral loads, making the former a more feasible measure for use.
An Overview of Food and Drug Administration Medical Device Legislation and Interplay with Current Medical Practices.

Since the emergence of medical devices, legislation has been developed to allow the Federal Drug Administration (FDA) to oversee their development, marketing, and usage. This paper discusses the history of the FDA's involvement in medical devices, current approval processes, and several case examples. Additionally, it discusses both short- and long-term effects with unexpected consequences to U.S. health care delivery.
Low-Dose Recombinante Urate Oxidase (Rasburicase) Is Effective in Hyperuricemia.

Hyperuricemia is a feature of tumor lysis syndrome (TLS), and is treated with hydration, urine alkalinization, and allopurinol. Allopurinol inhibits the conversion of hypoxanthine to xanthine, and xanthine to uric acid (UA) by inhibiting xanthine oxidase. It has no direct effect on existing UA. Rasburicase lowers UA rapidly to very low levels at the labeled dose of 0.15–0.2 mg/kg daily for 5 days by converting UA to allantoin which is rapidly excreted. Despite this dramatic effect on UA, rasburicase has not been shown to have any beneficial impact on survival. We administered 0.2 mg/kg ideal body weight rasburicase to an obese hyperuricemic patient (actual 120 kg, ideal 60 kg). Serum UA declined from 11 mg/dL to 1.4 mg/dL in 3 h and 0.4 mg/dL in 11 h. The serum UA level remained low for several days and a second dose was not needed. After seeing this dramatic and sustained response, low rasburicase doses were used in patients with malignant diseases with close monitoring of biochemical parameters. No dose level was systematically explored and the doses used ranged from 1.5 mg to 12 mg. This analysis is a retrospective review of all patients who received low-dose rasburicase. 23 adults (39–78 y) with cancer and hyperuricemia received a single low dose of rasburicase at 12 mg (n=1; index case), 6 mg (n=2), 4.5 mg (n=1), 3 mg (n=18), and 1.5 mg (n=1). 6 patients received 1 and 1 patient received 2 more doses of 3 mg each. Allopurinol and other supportive therapy including hydration were administered. UA levels (baseline 7.4–19 mg/dL, median 11.6) declined by 4–96% (median 40%) within 24 h of rasburicase administration (Fig 1; the dashed lines show patients receiving more than 1 rasburicase dose). The decline was 31–68% (median 46%) amongst the 12 patients receiving a single 3 mg dose (Fig 2). The baseline serum creatinine was 0.9–8.4 mg/dL (median 2.4), and the minimum and maximum values in the week following rasburicase were 0.7–5.8 (median 1.8) and 1.0–8.8 (median 2.6) respectively. No clinically significant renal dysfunction developed in any patient. The total rasburicase dose administered, 3–12 mg (median 3 mg), was 3–12% (median 5%) of the recommended dose. Based on the Red Book rasburicase cost of $387 for a 1.5 mg vial, the amount of money saved ranged from $11,000 to $29,000 per patient; for a total saving of between $373,000 and $507,000. While this was not a systematic dose-reduction study and patients were treated by multiple physicians and pharmacists on clinical grounds, the data suggest that rasburicase is effective at a fraction of the recommended dose. While a formal investigation of low doses is warranted, we recommend using rasburicase at a standard dose of 3 mg in hyperuricemic patients, checking UA levels frequently, and repeating rasburicase administration if needed. This approach has the potential for substantial cost saving while providing appropriate therapy to lower UA.
New Problems and Solutions in IoT Security and Privacy.

In a previous article for S&P magazine, we made a case for the new intellectual challenges in the Internet of Things security research. In this article, we revisit our earlier observations and discuss a few results from the computer security community that tackle new issues. Using this sampling of recent work, we identify a few broad general themes for future work.
A CANCER PATIENT WITH A BROKEN HEART

Immune checkpoint inhibitors have emerged as game changers for advanced cancer. Treatment-related cardiomyopathy is rare, but it's associated with severe adverse events. A 51-year-old male with recurrent stage IV rectal adenocarcinoma on pembrolizumab treatment with complicated perirectal abscess
Alice in Wonderland Syndrome Associated With a Temporo-Parietal Cavernoma (P5.124)

OBJECTIVE: In this case report, we relate a unique case of Alice in Wonderland Syndrome in a woman with a right temporo-parietal cavernoma. BACKGROUND: Alice in Wonderland Syndrome (AIWS) is a rare constellation of perceptual disturbances marked by distorted body image and metamorphopsia_ illusory changes in the form, size, distance, or color of stationary objects. Although the cause of AIWS is unclear, it has been associated with migraines, epilepsy, Ebstein-Barr virus infection, hallucinogen intoxication, and hypnogogic or hypnopompic states. DESIGN/METHODS: Case report and literature review. RESULTS: A 34 year-old pregnant woman presented with two weeks of “hearing voices” and “seeing things.” After having a generalized tonic-clonic seizure, she was started on levetiracetam. She had remission of the visual and auditory disturbances. Her EEG, which initially showed right temporal epileptiform activity, improved to showing right temporal slowing without epileptiform activity. Within several days, the patient began to have worsening symptoms: she heard voices of children crying and praying; she saw furniture and houses appearing as boxes, cars appearing as small circles, people having “pink feathery faces” with “long orange hair,” people turning into animals, objects moving forward and backwards, and people shrinking and then magnifying; she felt as if her hands had become “piano keys.” MRI of the brain revealed a right temporo-parietal cavernoma. With further increase of the levetiracetam, she had complete remission of her visual and auditory symptoms. CONCLUSIONS: Previously reported cases of AIWS involve epilepsy, and this patient was recently found to have temporal lobe seizures. However, the perceptual disturbances persisted despite adequate control of her seizure disorder as demonstrated by lack of epileptiform activity on EEG. An association between the right tempo-parietal cavernoma and this patient’s AIWS is reasonable. Alternatively, the symptoms of AIWS could represent a prolonged postictal phenomenon following right temporal lobe seizures. Disclosure: Dr. Kornitzer has nothing to disclose. Dr. Philips has nothing to disclose. Dr. Marks has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Souayah has received personal compensation for activities with Walgreens and Grifols as a consultant and/or speakers bureau participant.
Watershed or bank-to-bank? Scales of governance and the geographic definition of Great Lakes Areas of Concern:

Much recent scholarship has addressed the rise of the watershed as the preferred scale for the governance of water quality. Although the watershed remains widely perceived as an ideal, “natural” sc...
Design and Performance of an Inexpensive Water Activity Meter.

Water activity refers to the amount of water in a system that is available for microbial growth. Commercial water activity meters are precision instruments with the ability to determine water activity to within 0.001 units and carry prices of $10,000 or more. The purpose of the study was to build a robust water activity meter from commercially available components and measure the water activity of liquids commonly used in compounded formulations. SHT-85 sensors were connected to an Adafruit Feather HUZZAH microcontroller. Standard salt slurries and common oral liquid vehicles were monitored in airtight containers until equilibrium was reached. Standard curves were used to convert sensor outputs to water activity values. The standard curves were linear with R2 >0.99. Oral liquid vehicles showed water activity values between 0.62 and 0.99. Samples equilibrated within 9.5 hours in 16-ounce jars or 2.5 hours in 20-mL vials. Stirring the sample during measurement reduced equilibration time in 16-ounce jars, but not in 20-mL vials. The inexpensive meter was accurate and precise in measuring the water activity of standards and selected oral vehicles. An accurate and precise water activity meter was constructed at a cost of approximately $150. Common oral formulation components have a water activity of >0.6, the United States Pharmacopeial threshold for requiring a preservative. Pharmacists should use caution when diluting preserved vehicles.
Should CD4 Levels be Monitored in a Patient on Temozolomide

Introduction Temozolomide is an alkylating agent, indicated in the treatment of refractory anaplastic astrocytoma and newly diagnosed glioblastoma. We describe a case of Salmonella typhimurium bacteraemia associated with septic arthritis in the setting of concurrent temozolomide use. Case A 67-year-old woman presented with acute onset of bilateral knee pain and swelling. She had a medical history of glioblastoma multiforme treated with temozolomide. Synovial fluid analysis and blood cultures revealed S. typhimurium, confirming a diagnosis of S. typhimurium bacteraemia associated with septic arthritis. Conclusion We conclude that chemotherapy with temozolomide and corticosteroid use will increase an individual's susceptibility to a wide variety of opportunistic infections akin to HIV-associated acquired immunodeficiency syndrome (AIDS). Furthermore, we hypothesize a possible benefit of monitoring CD4 levels and prophylaxis against opportunistic infections (based on the CD4 levels) in individuals receiving temozolomide-based chemotherapy, similar to HIV-AIDS. Learning points Chemotherapy with temozolomide and corticosteroid use will increase an individual's susceptibility to a wide variety of opportunistic infections akin to HIV-associated acquired immunodeficiency syndrome (AIDS).There may be a benefit in monitoring CD4 levels in patients who are receiving temozolomide.Given selective CD4 lymphopenia while on temozolomide, there may be a possible benefit of prophylaxis against opportunistic infections in individuals based on their CD4 levels, similar to HIV-AIDS (current guidelines recommend considering Pneumocystis jirovecii pneumonia prophylaxis for patients receiving concomitant radiotherapy and temozolomide, and high-dose steroids).
'Don't Confuse Me with the Facts': The Use and Misuse of Social Science on the U.S. Supreme Court

This paper presents the first quantitative analysis of the conditions under which Supreme Court justices cite social science in their opinions. To set the stage, I review history of the role of social science in Supreme Court decisions from the Lochner Era through Brown v. Board of Education. I argue the utility of scientific evidence to the Court varies over time, as the social sciences co-evolved with the growth of the modern activist state. As the social sciences became increasingly quantitative in their approach, judges, who usually lack statistical training, are more likely to question the role of social science. A series of multivariate logistic regression analyses indicates scientific references are more likely to appear in salient cases. Justices who majored in a scientific discipline as an undergraduate are more likely to cite social science than others. Moreover, liberal justices are significantly more likely to cite social science research than conservatives. The relationship between social science and judicial behavior is not just partisan; it is polarizing. The data indicate justices on the Court’s left (and right) are more likely to invoke science in order to justify a liberal (conservative) opinion. This polarizing effect is even stronger in ideologically-congruent dissenting opinions.
Ichthyosis and hereditary cornification disorders in dogs

The stratum corneum (SC), the outermost layer of the epidermis, serves a crucial role in maintaining body hydration and protection from environmental insults. When the stratum corneum is injured or when the genetic blueprints are flawed, the body is at risk of dehydration, secondary infections and allergen sensitization. Advancements in veterinary dermatology have revealed a wide gamut of disease from relatively benign to lethal that specifically arise from flawed structural proteins, enzymes or lipids needed to create the corneocytes and lipid bilayers of the SC. Some conditions closely mimic their human counterparts while others are unique to the dog. This review will focus on forms of ichthyosis in the dog.
Mass Spectrometric Methods for Peptide Sequencing: Applications to Immunology and Protein Acylation

The earliest applications of tandem quadrupole mass spectrometry to sequence analysis of an unknown peptide [1] and a protein [2] required nanomoles of sample. Today, peptides in complex mixtures can be sequenced routinely on a Finnigan triple quadrupole instrument at the 10 femtomole level [3]. Microsequence analysis by the classical Edman degradation approach requires at least 10–100 times this amount of material, making mass spectrometry the most sensitive method in the world for this purpose. It is also the method of choice for characterizing posttranslational modifications. In this chapter, we discuss the mass spectrometric approach for sequencing naturally processed peptides bound to class I major histocompatibility complex molecules (MHC), and the methods used for the identification of an acylation site found in adenylate cyclase toxin.
Ocelli and Stemmata

Publisher Summary This chapter discusses the types of simple eyes in insects namely ocelli and stemmata. Until relatively recently, the simple eyes of both larvae and adults have been termed “ocelli” (ocellus), although it has been recognized that these are two different groups that are innervated from different parts of the brain. One group of simple eyes, found in adult insects and larvae of nonholometabolans, is termed “dorsal ocelli” or simply “ocelli.” These structures are innervated dorsally from the protocerebrum between the optic lobes. The second group of simple eyes, formerly termed “lateral ocelli” but now termed “stemmata” (singular stemma), is found in the larvae of Holometabola. Stemmata are innervated laterally from the optic lobes, and typically there is a group on each side of the head. The number of stemmata is variable, ranging from zero to seven, and the number and arrangement can be diagnostic.
The Dominican Charism and Higher Education: A Personal Reflection from the Field.

Providence College is part of a nation-wide consortium of nineteen Dominican colleges and universities. Every two years, one of these schools hosts the Dominican Colleges Colloquium , a conference focusing on how the Dominican charism can be effectively embodied, lived, and promoted in higher education. I have attended two of these colloquia over the past several years and have been enriched and challenged at each. Typically, more than 200 people gather to attend workshops, lectures, and seminars concerning our shared Dominican mission in Catholic higher education. Topics of discussion usually include best practices for enhancing mission, curriculum ideas, student life activities, and resources for ritual celebrations of the founding Dominican communities and saints. This article shares some of the wisdom I have acquired during these valuable gatherings.
Advancing the screening of fibromyalgia in late-life depression: practical implications for psychiatric settings.

Background: Fibromyalgia (FM) is common in older adults suffering from mood disorders. However, clinical diagnosis of FM is challenging, particularly in psychiatric settings. We examined the prevalence of FM and the sensitivity of three simple screeners for FM. Methods: Using cross-sectional data, we evaluated three tests against the American College of Rheumatology (ACR) 1990 Criteria for the Classification of FM: a “Do you often feel like you hurt all over?” question, a pain map score, and the Pope and Hudson (PH) interview for FM. Participants were 185 community-dwelling adults ≥ 60 years old with comorbid depression and chronic low back pain evaluated at a late-life mental health clinic. Results: Fifty three of 185 participants (29%) met the ACR 1990 FM criteria. Compared to those without FM, the FM group had more “yes” answers to the “hurt all over?” question and higher pain map scores. To reach a sensitivity of at least 0.90, the cut-off score for the pain map was 8. The sensitivity of the pain map, “hurt all over?” question, and PH criteria were 0.92 [95%CI 0.82–0.98], 0.91 [95%CI 0.79–0.97], and 0.94 [95%CI 0.843–0.99] respectively. Conclusions: Nearly one in three older adults suffering from depression and chronic low back pain met ACR 1990 FM criteria. Three short screening tests showed high sensitivity when compared to the ACR 1990 FM criteria. Implementation of one of the simple screeners for FM in geriatric psychiatry settings may guide the need for further diagnostic evaluation.
Treatment of high-level wastes from the IFR fuel cycle

The Integral Fast Reactor (IFR)1 is an advanced power reactor concept sponsored under the U. S. Department of Energy’s reactor development program.2 It promises to have important advantages over present reactors in its capability to conserve resources and consume the transuranic elements, thus excluding these from its wastes. It can also be used to consume the actinides in other nuclear wastes, such as spent light-water reactor fuels, and the transuranic (TRU) elements from nuclear weapons. The IFR features on-site reprocessing using pyrochemical methods to recover actinides from the U-Pu-Zr core and U-Zr blanket fuels, separate fission products, and produce suitable high-level waste forms. More than 99% of the TRU elements are recovered and separated from fission products by an electrorefining process at about 500°C.3 Treatment of electrorefiner wastes to recover residual actinides results in the recovery, recycle, and burnup of more than 99.9% of the TRU elements in discharged fuel. The electrorefiner (Figure 1) is a steel vessel that holds a pool of liquid cadmium (which serves as an anode in some operations) and a liquid LiCl-KCl electrolyte. Spent fuel elements are chopped, placed in steel baskets, and immersed in the electrolyte, where the fuel is anodically dissolved from the cladding. A major fraction of the uranium from the fuels is electrochemically deposited on steel cathode rods, and the rest of the uranium and the TRU elements are deposited in liquid cadmium cathodes. A significant fraction of the zirconium is also deposited with uranium on the solid cathodes. These cathodes are retorted to recover salt and cadmium, and melted to produce metal ingots for use in producing new core and blanket fuels.
Overview of high voltage 4H-SiC photoconductive semiconductor switch efforts at texas tech university

Recent advances and the current state-of-the-art for high speed 4H-SiC photoconductive semiconductor switches (PCSS) developed at Texas Tech University are summarized. A performance comparison of multiple generations of switch designs is also presented. These devices have experimentally demonstrated the capability of blocking DC electric fields up to 705 kV/cm (<0.1 mA leakage current), rise times of 0.63 ns (20/80), and switching 20 kV at 250 A with a di/dt of 75 kA/us at a burst repetition frequency of 65 MHz. Findings and optimizations pertaining to device geometry, sub-contact doping, contact thickness, triggering wavelength, and electron irradiation are presented. Device modeling and experimental results investigating current issues with device lifetime are presented as well.
Strong coupling regime in two-dimensional large-N scalar quantum chromodynamics

Two-dimensional large-$N$ quantum chromodynamics with scalar quarks is considered with particular emphasis on its strong coupling regime which has not been studied so far. Techniques necessary to deal with the infinitely oscillatory bound state wave functions in the strong coupling regime are developed. I derive an estimate for the ground state mass and show that (1) the lightest hadron in the theory is massless and (2) the ground state mass is continuous across the transition between the weak and the strong coupling.
Editorial: Debating the links between education, training and national growth-An exercise in the design of compelling arguments, or affect versus intellect.

The article discusses the social role of higher education in Africa and analyzes debate questions and strategy on the link between education, vocational training, and economic development. Other topics include the economic growth of South Korea, labor skill training in Brazil, and rules and procedures for debates.
PHOSPHORYLATION OF RAF-1 SERINE 338-SERINE 339 IS AN ESSENTIAL REGULATORY EVENT FOR RAS-DEPENDENT ACTIVATION AND BIOLOGICAL SIGNALING

Activation of the Raf serine/threonine protein kinases is tightly regulated by multiple phosphorylation events. Phosphorylation of either tyrosine 340 or 341 in the catalytic domain of Raf-1 has been previously shown to induce the ability of the protein kinase to phosphorylate MEK. By using a combination of mitogenic and enzymatic assays, we found that phosphorylation of the adjacent residue, serine 338, and, to a lesser extent, serine 339 is essential for the biological and enzymatic activities of Raf-1. Replacement of S338 with alanine blocked the ability of prenylated Raf-CX to transform Rat-1 fibroblasts. Similarly, the loss of S338-S339 in Raf-1 prevented protein kinase activation in COS-7 cells by either oncogenic Ras[V12] or v-Src. Consistent with phosphorylation of S338-S339, acidic amino acid substitutions of these residues partially restored transforming activity to Raf-CX, as well as kinase activation of Raf-1 by Ras[V12] or v-Src. Two-dimensional phosphopeptide mapping of wild-type Raf-CX and Raf-CX[A338A339] confirmed the presence of a phosphoserine-containing peptide with the predicted mobility in the wild-type protein which was absent from the mutant. This peptide could be quantitatively precipitated by an antipeptide antibody specific for the 18-residue tryptic peptide containing S338-S339 and was demonstrated to contain only phosphoserine. Phosphorylation of this peptide in Raf-1 was significantly increased by coexpression with Ras[V12]. These data demonstrate that Raf-1 residues 338 to 341 constitute a unique phosphoregulatory site in which the phosphorylation of serine and tyrosine residues contributes to the regulation of Raf by Ras, Src, and Ras-independent membrane localization.
Left-Sided Cardiac Valvulitis in Tristetraprolin-Deficient Mice: The Role of Tumor Necrosis Factor α

Inflammation may play a role in the etiology of both degenerative and rheumatic cardiac valve diseases. We report here that mice deficient in tristetraprolin (TTP), a protein with known anti-inflammatory functions, develop severe left-sided cardiac valvulitis. TTP is an mRNA binding protein that inhibits inflammation by destabilizing the mRNA encoding tumor necrosis factor α (TNF). This leads in turn to a TNF-excess syndrome characterized by systemic inflammation. Evaluation of hearts from TTP −/− mice demonstrated gross thickening of the mitral and aortic but not the tricuspid or pulmonary valves, accompanied by inflammatory cell infiltrates. To determine whether TNF played a role in the development of this valvulitis, we examined mice deficient in both TNF receptors and in TTP; four of five of these mice exhibited no histological evidence of valvulitis, but one mouse had aortic valve leaflet thickening with a cellular infiltrate. Four additional mice had no external evidence of valvular thickening. Cardiac valves of transgenic mice expressing human TNF developed mild aortic valve leaflet edema without evidence of hypercellularity. Thus, TTP deficiency in mice leads to left-sided cardiac valvulitis with prominent inflammatory cell involvement, due, at least in part, to excess TNF. These findings support the potential involvement of TNF and inflammation in the development of cardiac valve disease in man.
Phosphatidylinositol 3,4,5-trisphosphate directs association of Src homology 2-containing signaling proteins with gelsolin.

Podosomes are adhesion structures in osteoclasts and are structurally related to focal adhesions mediating cell motility during bone resorption. Here we show that gelsolin coprecipitates some of the focal adhesion-associated proteins such as c-Src, phosphoinositide 3-kinase (PI3K), p130Cas, focal adhesion kinase, integrin αvβ3, vinculin, talin, and paxillin. These proteins were inducibly tyrosine-phosphorylated in response to integrin activation by osteopontin. Previous studies have defined unique biochemical properties of gelsolin related to phosphatidylinositol 3,4,5-trisphosphate in osteoclast podosomes, and here we demonstrate phosphatidylinositol 3,4,5-trisphosphate/gelsolin function in mediating organization of the podosome signaling complex. Overlay and GST pull-down assays demonstrated strong phosphatidylinositol 3,4,5-trisphosphate-PI3K interactions based on the Src homology 2 domains of PI3K. Furthermore, lipid extraction of lysates from activated osteoclasts eliminated interaction between gelsolin, c-Src, PI3K, and focal adhesion kinase despite equal amounts of gelsolin in both the lipid-extracted and unextracted experiment. The cytoplasmic protein tyrosine phosphatase (PTP)-proline-glutamic acid-serine-threonine amino acid sequences (PEST) was also found to be associated with gelsolin in osteoclast podosomes and with stimulation of αvβ3-regulated phosphorylation of PTP-PEST. We conclude that gelsolin plays a key role in recruitment of signaling proteins to the plasma membrane through phospholipid-protein interactions and by regulation of their phosphorylation status through its association with PTP-PEST. Because both gelsolin deficiency and PI3K inhibition impair bone resorption, we conclude that phosphatidylinositol 3,4,5-trisphosphate-based protein interactions are critical for osteoclast function.
Liberation From Mechanical Ventilation: A Decade of Progress

Multiple complications associated with mechanical ventilation mandate that clinicians expeditiously define and reverse the pathophysiologic processes that precipitate respiratory failure and then, detect the earliest point that a patient can breathe without the ventilator. Over the past decade, numerous laboratory and clinical studies have been reported that may inform transformation of the “art of weaning” to the science of liberation. We review these studies and use them to formulate a systematic approach to assure early, safe, and successful liberation of patients from mechanical ventilation. (CHEST 1998; 114:886–901) Abbreviations: CO 2 =carbon dioxide; CPAP=continuous positive airway pressure; CROP=compliance, rate, oxygenation, pressure; Crs=respiratory system compliance; MVV=maximum voluntary ventilation; NIPPV=noninvasive positive-pressure ventilation; P 0.1 = airway occlusion pressure; PEEP=positive end-expiratory pressure; pHi=intramucosal pHi; PImax=maximum inspiratory pressure; PSV=pressure-support ventilation; RF=respiratory failure; ROC=receiver operating characteristic; RVR=rate:volume ratio (respiratory rate:tidal volume ratio); SIMV=synchronized intermittent mandatory ventilation; VA=alveolar ventilation; V ˙ co 2 =carbon dioxide output; VD=dead space ventilation; V ˙ E=minute volume
Efficacy of Antiretroviral Therapy Adherence Interventions: A Research Synthesis of Trials, 1996 to 2004

Objective: To conduct a quantitative review of published trials of antiretroviral therapy (ART) adherence interventions. Design: A research synthesis of published ART adherence intervention outcome studies. Sample: ART adherence intervention outcome studies meeting inclusion criteria published between 1996 and December 2004 (k = 24). Main Outcome Measure: Effect sizes (ESs [d]) were calculated for each study outcome, producing 25 immediate postintervention outcomes and an additional 13 follow-up ESs. Reported pre- to post-ART adherence between groups (k = 15) or within groups (k = 10) served as the main outcome converted to standardized ES. Results: ART adherence interventions had a small effect (d = 0.35, odds ratio [OR] = 1.88) that varied considerably across studies. Interventions that specifically enrolled participants with known or anticipated problems with ART adherence demonstrated medium effects on adherence (d = 0.62, OR = 3.07). Interventions that did not target their participants on similar criteria had quite small effects (d = 0.19, OR = 1.41). Adherence improvements showed no tendency to decay across time. Conclusions: Outcomes of studies targeting those with poor ART adherence had stronger effects than those intervening with groups of individuals who were mixed in terms of pretest levels of adherence. Adherence intervention outcome studies must carefully delineate their target populations, because defining individuals as "on ART" does not provide the level of specificity needed to design and implement effective interventions.
Localized algorithms for coverage boundary detection in wireless sensor networks

Connected coverage, which reflects how well a target field is monitored under the base station, is the most important performance metric used to measure the quality of surveillance that wireless sensor networks (WSNs) can provide. To facilitate the measurement of this metric, we propose two novel algorithms for individual sensor nodes to identify whether they are on the coverage boundary, i.e., the boundary of a coverage hole or network partition. Our algorithms are based on two novel computational geometric techniques called localized Voronoi and neighbor embracing polygons. Compared to previous work, our algorithms can be applied to WSNs of arbitrary topologies. The algorithms are fully distributed in the sense that only the minimal position information of one-hop neighbors and a limited number of simple local computations are needed, and thus are of high scalability and energy efficiency. We show the correctness and efficiency of our algorithms by theoretical proofs and extensive simulations.
Theory of the potential energy boundary surface

In this paper we provide a theoretical foundation of the PEBS method. First, we study the properties of the stability boundary of a gradient system. We then relate the stability boundary of a class of second-order dynamical systems to the gradient system. Using these results, we analyze the PEBS method. Conditions under which the PEBS method gives accurate stability estimate are discussed.