cssi/SciSciGPT-SciSciNet huggingface dataset:
Customized biomaterials to augment chondrocyte gene therapy.

Abstract A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications. The transient exposure of cells to the product could be insufficient to promote tissue regeneration. Here we report the development of a new material engineered to have a high affinity for a therapeutic gene product. We focus on insulin-like growth factor-I (IGF-I) for its highly anabolic effects on many tissues such as spinal cord, heart, brain and cartilage. One of the ways that tissues store IGF-I is through a group of insulin like growth factor binding proteins (IGFBPs), such as IGFBP-5. We grafted the IGF-I binding peptide sequence from IGFBP-5 onto alginate in order to retain the endogenous IGF-I produced by transfected chondrocytes. This novel material bound IGF-I and released the growth factor for at least 30 days in culture. We found that this binding enhanced the biosynthesis of transfected cells up to 19-fold. These data demonstrate the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly, and can serve as a template for the enhanced performance of other therapeutic proteins. Statement of Significance The present manuscript focuses on the enhancement of chondrocyte gene therapy through the modification of scaffold materials to enhance the retention of targeted gene products. This study combined tissue engineering and gene therapy, where customized biomaterials augmented the action of IGF-I by enhancing the retention of protein produced by transfection of the IGF-I gene. This approach enabled tuning of binding of IGF-I to alginate, which increased GAG and HYPRO production by transfected chondrocytes. To our knowledge, peptide-based modification of materials to augment growth factor-targeted gene therapy has not been reported previously.
Microbes Are Associated with Host Innate Immune Response in Idiopathic Pulmonary Fibrosis

Rationale: Differences in the lung microbial community influence idiopathic pulmonary fibrosis (IPF) progression. Whether the lung microbiome influences IPF host defense remains unknown.Objectives: To explore the host immune response and microbial interaction in IPF as they relate to progression-free survival (PFS), fibroblast function, and leukocyte phenotypes.Methods: Paired microarray gene expression data derived from peripheral blood mononuclear cells as well as 16S ribosomal RNA sequencing data from bronchoalveolar lavage obtained as part of the COMET-IPF (Correlating Outcomes with Biochemical Markers to Estimate Time-Progression in Idiopathic Pulmonary Fibrosis) study were used to conduct association pathway analyses. The responsiveness of paired lung fibroblasts to Toll-like receptor 9 (TLR9) stimulation by CpG-oligodeoxynucleotide (CpG-ODN) was integrated into microbiome–gene expression association analyses for a subset of individuals. The relationship between associated pathways and circulating l...
Utilization of kudzu as a lead phytoremediator and the impact of lead on selected physiological responses

Schwarzauer-Rockett, K., Al-Hamdani, S. H., Rayburn, J. R. and Mwebi, N. O. 2013. Utilization of kudzu as a lead phytoremediator and the impact of lead on selected physiological responses. Can. J. Plant Sci. 93: 951–959. This study was carried out to evaluate kudzu [Pueraria montana var. lobata (Willd.)] in lead phytoremediation. The impact of lead (PbNO3) concentrations of 100 and 200 mg L−1 on plant growth, photosynthetic pigments, photosynthesis, and stomatal conductance were evaluated. Additionally, concentrations of phenolic compounds and anthocyanin were determined. The lead was dissolved in 0.142 g L−1 ethylenediaminetetraacetic acid (EDTA) and an EDTA control treatment was added to evaluate the impact of EDTA on the above selected plant responses. Root accumulation of lead was significantly higher than in the shoot. Kudzu growth in response to the presence of lead and EDTA in the Hoagland's solution was similar to that of the EDTA control, except for plants growing at 200 mg L−1, which showed sign...
Winning with Pinning: Enhancing Health and Physical Education with Pinterest

Social media can enhance teaching and learning by contributing to a quality health and physical education (HPE) program. Social networking has equipped HPE teachers with many novel resources for use in their classrooms. Pinterest (www.pinterest.com) is a social media website that allows teachers to search and find lesson ideas and professional development opportunities, collaborate and network with other professionals, share resources with students, and provide a platform for family and community involvement. This article presents an overview of the use of Pinterest for HPE teachers.
Observability, Predictability and Chaos

The purpose of this paper is to examine in detail the questions involved in Example 10 of Martin’s article (also in this volume). It arises from the following very general question. Given a manifold with a flow on it and given a real valued function of the manifold, under what circumstances can the function distinguish orbits of different points? That is, if h ∈ C ∞(M) and φ is the flow, then if $$h(\Phi (x,t)) = h(\Phi (y,t))$$ for all t, does this imply that x= y? If so, we say h observesthe pair (M, φ), or that the triple (M,φ,h) is observable.
Dealing with Monetary Paralysis at the Zero Bound

Recently, the key constraint for central banks is the zero lower bound on nominal interest rates. Central banks fear that if they push short-term policy interest rates too deeply negative, there will be a massive flight into paper currency. This paper asks whether, in a world where paper currency is becoming increasingly vestigial outside small transactions (at least in the legal, tax compliant economy), there might be relatively simple ways to finesse the zero bound without affecting how most ordinary people live. Surprisingly, this question gets little attention compared to the massive number of articles that take the zero bound as given and look for out-of-the-box solutions for dealing with it. In an inversion of the old joke, it is a bit as if the economics literature has insisted on positing "assume we don't have a can opener," without considering the possibility that we might be able to devise one. It makes sense not to wait until the next financial crisis to develop plans. Fundamentally, there is no practical obstacle to paying negative (or positive) interest rates on electronic currency and, as we shall see, effective negative rate policy does not require eliminating paper currency.
The Pathophysiological Basis of Hypercalciuria in Primary Hyperparathyroidism

When initially described in the mid-1920’s, primary hyperparathyroidism (l°HPT) was regarded as a rare and severe disorder of bone. Shortly thereafter, Albright and colleagues recognized a different clinical presentation of l°HPT in patients with renal stones who lacked evidence of overt bone disease1. It subsequently became clear that renal stones are a far more frequent complication of l°HPT than overt osteitis, being the presenting complaint in approximately 50% of patients2. Further, it was recognized that patients presenting with stones rarely display evidence of clinical bone involvement and that patients presenting with clinical bone disease only rarely gave a history of renal stones (nephrocalcinosis was variably observed in a minority of patients with both presentations). Thus, early investigators were impressed by reasonably distinctive “bone” and “stone” presentations of the disorder and offered several hypotheses in attempt to explain their observations. These included Albright’s “dietary calcium” hypothesis1. Dent’s “dual hormone” hypothesis3, and the general proposal that clinical bone involvement developed as a function of the duration of the disease. Although Albright’s general tenets concerning external calcium balance were later supported by the observation of negative balance in patients with overt bone disease and zero or even positive balance in patients with stone disease4. All three hypotheses were subsequently either disproven or could not be supported by the accumulated evidence2. Thus, the clinical “spectrum” of the disorder remained enigmatic well through the 1960’s.
Behavior Therapy in Education

A great deal of research was conducted during the 1960s on the application of behavioral principles in classroom management. This initial interest seems to have waned in the 1970s as indicated by a marked decline in relevant research. This decline reflects, in part, the typical shifting of fads and fashions in science; but the misconception that there is no more to be learned from research in this area also seems to be a factor. This unfortunate conclusion stems from many sources, but is perhaps primarily attributable to our failure to question the role of classroom behavior modification programs in a broader social context. What is the purpose of public education? What is the role of behavior modification in this context? Is it only to keep children docile for six hours a day? There is still much to be learned.
Alzheimer’s Disease Causes Metabolic Uncoupling of Associative Brain Regions Beyond that Seen in the Healthy Elderly

Alzheimer’s disease (AD) is a progressive degenerative brain disorder that has no agreed-upon cause. The earliest and most prominent neuropsychological deficit is recent memory impairment, which usually is attributed to pathological and neurochemical changes in the hippocampus, amygdala and neocortex (3, 5, 32). The first cognitive deficits to appear that are related to neocortical dysfunction are impairments of attention, abstract reasoning, language and visuospatial construction (18, 20, 21).
Fresh Brain Tissue Diagnostics Using Raman Spectroscopy in Humans

A key part of treatment for brain tumors is tumor resection, the amount of tumor resection has a direct correlation on the mortality of the patient. However, tools available to surgeons to ensure maximal resection while preserving a patient's functional status often increase surgery time or are lacking in accuracy. Raman spectroscopy is a promising modality that can provide real time intraoperative data to the surgeon about whether a tissue is normal or cancerous, thus aiding the surgeon in obtaining maximal safe resection. In this paper, we pair Raman spectroscopy with a supervised machine learning technique, support vector machine, to classify fresh tissue samples as solid tumor, infiltrating tumor, necrosis, or normal brain tissue. The support vector machine classifier resulted in 89% accuracy of the 117 tissue samples while delivering real time results. Accurate real-time tissue characterization will vastly reduce the amount of time a surgeon waits for the results of biopsies and provides a means for intraoperative margin assessment during tumor resection.
Cauchy transforms arising from homomorphic conditional expectations parametrize noncommutative Pick functions

Abstract Nevanlinna showed that Cauchy transforms of probability measures parametrize all functions from the upper half plane into itself satisfying a certain asymptotic condition at infinity. We show that the correspondence fails in general for the unbounded case for somewhat trivial reasons; however, we show that in a setting of “homomorphic” operator valued free probability that Cauchy transforms of homomorphic conditional expectations parametrize noncommutative Pick functions.
Genotype-Phenotype Correlation in Congenital LQTS: Implications for Diagnosis and Risk Stratification

The hereditary long QT syndrome (LQTS) is a genetic channelopathy with variable penetrance that is associated with increased propensity to syncope, polymorphic ventricular tachycardia (torsade de pointes), and sudden arrhythmic death. This inherited cardiac disorder constitutes an important cause of malignant ventricular arrhythmias and sudden cardiac death in young individuals with normal cardiac morphology. Diagnosis relies on combined assessment of ECG and clinical factors related to the patient’s personal and family history and may be difficult in approximately one quarter of LQTS subjects who present with a normal range QTc. Genetic testing is important for both diagnosis and risk assessment. Accumulating data from the International LQTS Registry have facilitated a comprehensive analysis of risk factors for aborted cardiac arrest or sudden cardiac death in prespecified age-groups, including the childhood, adolescence, adulthood, and post-40 years periods. These analyses have consistently indicated that the phenotypic expression of LQTS is time-dependent and age- and sex-specific, warranting continuous risk assessment in affected patients. Furthermore, the biophysical function, type, and location of the ion-channel mutation are currently emerging as important determinants of outcome in genotyped patients. These new data may be utilized to improve risk stratification and for the development of gene-specific therapies that may reduce the risk of life-threatening cardiac events in patients with this inherited cardiac disorder.
A Shift in Hip Arthroscopy Use by Patient Age and Surgeon Volume: A New York State-Based Population Analysis 2004 to 2016.

Purpose To perform a population-level analysis of the shifts in use of hip arthroscopy by different age groups and to describe the proportion of hip arthroscopy procedures performed by high-volume surgeons. Methods The Statewide Planning and Research Cooperative System database was combined with New York State census data to calculate changes in annual hip arthroscopy incidence by age and gender (2004-16). Annual (January to January) surgeon volumes were calculated and stratified into 4 thresholds that have been associated with significant differences in revision hip surgery rates to calculate changes in hip arthroscopy rates by surgeon volume over time. Results There was a 495% increase in hip arthroscopies from 2004 to 2016, from 2.35 to 15.47 per 100,000 residents in New York State. The largest increase was in the 10-19 years age group—a 2,150% increase for female patients (= 1.26, P Conclusions The use of hip arthroscopy has increased over the past 10 years, especially in the adolescent population ages 10-19. Over the same time period, there has been an emergence of high-volume hip arthroscopy surgeons and an increased proportion of procedures performed by these surgeons. Patients of high-volume surgeons tend to be younger, while lower volume surgeons tend to have older patients. Level of Evidence Level IV, case series.
Thermal and economic analysis of preinsulated and twin-pipe heat network operation

Abstract This study focuses on the economic analysis of the heating network modernization by using preinsulated pipes and twin-pipes. The cost analysis is based on different type, diameter, and technological diagrams of different heating network pipe variants (from DN25to DN100) and various types of insulation. Net present value (NPV) analysis comparing a five variants of the heating network pipes (Case 0: Pipes with insulation PUR standard; Case 1: Pipes with insulation PUR plus; Case 2: Pipes with insulation PEX standard; Case 3: Twin-Pipes with insulation PUR; Case 4: Twin-Pipes with insulation PEX). The value of NPV, which is the highest (NPV = 7000 €, DN65, case 2 and NPV = 5200 €, DN50, case 4) among presented variants is the best choose to consider during the investment. Despite the higher prices of Twin Pipe system, they are more profitable due to shallow heat transfer losses. Heat losses are calculated for various heating networks, including preinsulated and twin-pipe heating networks. The remaining heat loss calculation is based merely on temperature levels and thermal resistance factors (in the ground), determined using the pipe dimensions and materials. It is found that the most cost-effective from an economic point of view is the use of TwinPipe system. These pipes are more expensive, but the heat losses that occurs during their use are much smaller compared to preinsulated pipes. Short return time of such an investment (6–7 years) with 100 m of pipe installed and positive NPV causes that this type of pipes is the best investment in the case of district heating networks. The results shown that Case 3 (PEX insulation) is more economicaly beneficial than Case 4 (PUR insulation).
Activity Patterns and Foraging Behavior of American Pikas (Ochotona princeps) Differ between Craters of the Moon and Alpine Talus in Idaho

Range contractions in the Great Basin over the last century suggest that American pikas (Ochotona princeps) might be highly sensitive to climate change. However, documentation of pikas residing at relatively warm, low-elevation sites has recently shed new light on the possible resilience of pika populations to warmer ambient conditions when they have access to cooler microhabitats for thermoregulation. To provide insight into the possible behavioral mechanisms of adaptation to warmer habitats, we investigated activity patterns, foraging behavior, and space use of a population of pikas living in an atypical, warmer habitat at Craters of the Moon National Monument and Preserve, an extensive lava flow surrounded by high desert grassland and sagebrush communities in southern Idaho. We compared pika behavior at this site to that of a population in a more typical alpine habitat at Grays Peak in the nearby Pioneer Mountains in Idaho. Specifically, we evaluated and compared activity patterns and foraging behavior of pikas in relation to temperature, time of day, and month. Pikas at Craters of the Moon were less active aboveground during all times of the day from late May until mid-August, compared to those at Grays Peak. Surface temperatures were warmer across the entire season at Craters of the Moon than at Grays Peak, and pikas exhibited a crepuscular activity pattern that coincided with variations in surface temperature at Craters of the Moon. Pikas were the least active during the midday, when the surface temperatures were highest and the insulating effect of the lava tubes (i.e., the difference between surface and crevice temperatures) was most pronounced. Pikas at Craters of the Moon spent less time haying and displayed fewer territorial behaviors than pikas at Grays Peak, but both groups filled a similar number of hay piles. The vegetation community was less diverse and sparser at Craters of the Moon than at Grays Peak, and consequently, the vegetation that was consumed and cached reflected these differences. Our results expand the body of literature about American pikas at their environmental limits, and this study is the first step in identifying the unique suite of behaviors that pikas use to persist in a seemingly inhospitable environment at Craters of the Moon.
Cancer Progress and Priorities: Childhood Cancer

It is estimated that 300,000 children 0–19 years of age are diagnosed with cancer worldwide each year ([1][1]). In high-income countries, cancer is the leading cause of death due to disease in children. The absolute risk of cancer in children is, however, quite low [183 cases per million in the
Detailed wheel/rail geometry processing using the planar contact approach

The use of detailed wheel/rail contact models has long been frustrated by the complicated preparations needed, to analyse the profiles for the local geometry and creep situation for the planar cont...
Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors.

Abstract The sphingosine 1-phosphate (S1P) signaling pathway is an attractive target for pharmacological manipulation due to its involvement in cancer progression and immune cell chemotaxis. The synthesis of S1P is catalyzed by the action of sphingosine kinase 1 or 2 (SphK1 or SphK2) on sphingosine and ATP. While potent and selective inhibitors of SphK1 or SphK2 have been reported, development of potent dual SphK1/SphK2 inhibitors are still needed. Towards this end, we report the structure–activity relationship profiling of 2-(hydroxymethyl)pyrrolidine-based inhibitors with 22d being the most potent dual SphK1/SphK2 inhibitor (SphK1 Ki = 0.679 μM, SphK2 Ki = 0.951 μM) reported in this series. 22d inhibited the growth of engineered Saccharomyces cerevisiae and decreased S1P levels in histiocytic lymphoma myeloid cell line (U937 cells), demonstrating inhibition of SphK1 and 2 in vitro. Molecular modeling studies of 22d docked inside the Sph binding pocket of both SphK1 and SphK2 indicate essential hydrogen bond between the 2-(hydroxymethyl)pyrrolidine head to interact with aspartic acid and serine residues near the ATP binding pocket, which provide the basis for dual inhibition. In addition, the dodecyl tail adopts a “J-shape” conformation found in crystal structure of sphingosine bound to SphK1. Collectively, these studies provide insight into the intermolecular interactions in the SphK1 and 2 active sites to achieve maximal dual inhibitory activity.
The tone system of Poko-Rawo (Skou)

This paper describes the tone system of Poko-Rawo, a Skou language spoken in northwestern Papua New Guinea. The system displays a number of points of interest to tonal typology, including: a distinction between underlying specified Mid tones and M tones filled in by default; a dispreference for single-toned melodies; a preference for rising tones rather than falling tones; and strict alignment of Low and High tones, with L always initial and H always final in a melody. These alignment principles extend to floating tones, as floating L is always to the left of a stem and floating H always to the right. We provide a detailed description of underlying melodies, postlexical processes, and phonetic realization of tone in Poko in an effort to bring more Papuan data to bear on questions of tonal typology.
A Philosopher Looks at Human Beings

Why do we think ourselves superior to all other animals? Are we right to think so? In this book, Michael Ruse explores these questions in religion, science and philosophy. Some people think that the world is an organism - and that humans, as its highest part, have a natural value (this view appeals particularly to people of religion). Others think that the world is a machine - and that we therefore have responsibility for making our own value judgements (including judgements about ourselves). Ruse provides a compelling analysis of these two rival views and the age-old conflict between them. In a wide-ranging and fascinating discussion, he draws on Darwinism and existentialism to argue that only the view that the world is a machine does justice to our humanity. This new series offers short and personal perspectives by expert thinkers on topics that we all encounter in our everyday lives.
The Power of Semi-Public Communication

I study how an informed manager can benefit from cheap-talk communication by strategically forming diverse groups of uninformed, heterogenous workers. Optimal grouping, or partition, of workers trades off the benefit from gaining credibility through having greater diversity in each group against the cost from the inability to tailor communication among workers in the same group. Public and private communication are restrictions on the partitions the manager can adopt, and the manager prefers semi-public communication whenever there is a possibility to benefit from differently diverse groups of workers. I show that it is optimal for the manager to separate workers who need to be persuaded from those that do not, and I derive further properties of optimal partitions when workers are single minded and when workers have preferences over a spectrum of project types.
IGFBP-3 Mediates Metabolic Homeostasis During Hyperosmolar Stress in the Corneal Epithelium.

Purpose The insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional secretory protein with well-known roles in cell growth and survival. Data in our laboratory suggest that IGFBP-3 may be functioning as a stress response protein in the corneal epithelium. The purpose of this study is to determine the role of IGFBP-3 in mediating the corneal epithelial cell stress response to hyperosmolarity, a well-known pathophysiological event in the development of dry eye disease. Methods Telomerase-immortalized human corneal epithelial (hTCEpi) cells were used in this study. Cells were cultured in serum-free media with (growth) or without (basal) supplements. Hyperosmolarity was achieved by increasing salt concentrations to 450 and 500 mOsM. Metabolic and mitochondrial changes were assessed using Seahorse metabolic flux analysis and assays for mitochondrial calcium, polarization and mtDNA. Levels of IGFBP-3 and inflammatory mediators were quantified using ELISA. Cytotoxicity was evaluated using a lactate dehydrogenase assay. In select experiments, cells were cotreated with 500 ng/mL recombinant human (rh)IGFBP-3. Results Hyperosmolar stress altered metabolic activity, shifting cells towards a respiratory phenotype. Hyperosmolar stress further altered mitochondrial calcium levels, depolarized mitochondria, decreased levels of ATP, mtDNA, and expression of IGFBP-3. In contrast, hyperosmolar stress increased production of the proinflammatory cytokines IL-6 and IL-8. Supplementation with rhIGFBP-3 abrogated metabolic and mitochondrial changes with only marginal effects on IL-8. Conclusions These findings indicate that IGFBP-3 is a critical protein involved in hyperosmolar stress responses in the corneal epithelium. These data further support a new role for IGFBP-3 in the control of cellular metabolism.
Design of A Robust Noncontact Vital Signs (NCVS) Monitoring System Using Software defined radio (SDR)

A Doppler-based robust non-contact vital signs (NCVS) sensor system designed using a commercial software defined radio (SDR) box with LabView programming is reported in this work. The NCVS sensing system is designed to operate at the 2.4 GHz ISM band and with optimized transmit/receive settings on gain, filtering, intermediate frequency (IF), antenna placement, etc. We will describe the system GUI (graphic user interface) and the basic software and hardware design considerations and setup for this SDR-enable NCVS system. Our measurement data demonstrates that it can continuously monitor the real-time respiration rate (RR) and heart rate (HR) of student volunteers sitting in a chair 1.3 meters away consistently within 0.5/3 BPM (breath/beat per minute) compared with the reference RR/HR signals, respectively.
The Authenticity and Authority of Islam

This paper examines the concept of Islamic authority in relation to early twentieth-century Protestant missionary writings on Islam and Muhammad Rashid Rida’s commentaries on mission publications in his Cairo-based journal, al-Manar. While Rida’s Salafi reformism has been the subject of much discussion, scholars have given little attention to the content of the missionary writings Rida engaged. Treatments of Rida’s work have also neglected to address the vision of Islamic authority that emerges from his responses to Christian polemics. This paper gives both subjects further consideration as it discusses Protestant missionary approaches to Islam, examines Rida’s writings on Christianity, and assesses his response to a widely circulated article on Islam by Temple Gairdner, a prominent British missionary with the Church Missionary Society in Egypt.
Dynamic regulation of erythropoiesis: a computer model of general applicability.

A mathematical model for the control of erythropoiesis was developed based on the balance between oxygen supply and demand at a renal oxygen detector which controls erythropoietin release and red cell production. Feedback regulation of tissue oxygen tension is accomplished by adjustments of hemoglobin levels resulting from the output of a renal-bone marrow controller. Special consideration was given to the determinants of tissue oxygenation including evaluation of the influence of blood flow, capillary diffusivity, oxygen uptake and oxygen-hemoglobin affinity. A theoretical analysis of the overall control system is presented. Computer simulations of altitude hypoxia, red cell infusion hyperoxia, and homolytic anemia demonstrate validity of the model for general human application in health and disease.
Multidimensional Perceptions of Illness and Injury

This paper investigates the multidimensional nature of how we perceive physical illness and injury, and differences in those perceptions based on experience. Multidimensional scaling revealed that similarity judgments of 15 medical conditions made by registered nurses, undergraduate nursing students, and liberal arts students were based primarily on their functional impact to the individual (e.g., correctability and impact on long-term motor and sensory function). The less experienced students, however, also viewed the injuries more in terms of surface similarity (e.g., amputation, disfigurement, and sensory loss) than the registered nurses. The implications of the findings for decision making in personal injury cases are discussed.
Data compression and bioinformatics searching for structure in all kinds of places

At the heart of data compression is the search for how information is organized in data. This search for organization can focus on the data itself, on the source of the information, or on the sink, or user of the information. Analogous approaches can be used to identify how information is organized in the DNA sequence. In this talk we describe how techniques which have proven useful in developing compression algorithms are also capable of helping uncover organizational structures in DNA sequences. We also show how this process of discovery can lead to the development of tools which are useful in investigating and perha ps understanding genomic sequences.
Inositol 1,4,5-Triphosphate-Evoked Responses in Midbrain Dopamine Neurons

Synaptically released glutamate evokes slow IPSPs mediated by metabotropic glutamate receptors (mGluRs) in midbrain dopamine neurons. These mGluR IPSPs are caused by release of Ca(2+) from intracellular stores and subsequent activation of small-conductance Ca(2+)-activated K(+) channels (SK channels). To further investigate the intracellular mechanisms involved, the effect of photolyzing intracellular caged inositol 1,4,5-triphosphate (InsP(3)) on membrane conductance and intracellular Ca(2+) concentration ([Ca(2+)](i)) was examined in rat midbrain slices. Photolytic release of InsP(3) elicited a transient outward current and a sharp rise in [Ca(2+)](i) that lasted for approximately 5 sec. Apamin, a blocker of SK channels, abolished the InsP(3)-induced outward current without affecting the rise in [Ca(2+)](i). Depleting intracellular Ca(2+) stores with cyclopiazonic acid completely blocked both the outward current and the Ca(2+) transient elicited by InsP(3). InsP(3)-evoked Ca(2+) mobilization was not affected by blockade of ryanodine receptors with ruthenium red, whereas depleting ryanodine-sensitive Ca(2+) stores with ryanodine almost eliminated InsP(3)-induced Ca(2+) release. Increasing the size of intracellular Ca(2+) stores by means of prolonged depolarization added a late component to the outward current and a slow component to the rising phase of [Ca(2+)](i). These effects of depolarization were blocked by ruthenium red. These results show that InsP(3) activates SK channels by releasing Ca(2+) from InsP(3)-sensitive stores that also contain ryanodine receptors. Increasing intracellular Ca(2+) stores boosts InsP(3)-evoked responses by invoking Ca(2+)-induced Ca(2+) release through ryanodine receptors. This intracellular signaling pathway may play a significant role in regulating the excitability of midbrain dopamine neurons.
Physicians' perceptions of the Thrombolysis in Myocardial Infarction (TIMI) risk score in older adults with acute myocardial infarction.

Abstract Objectives To evaluate physician-perceived strengths and limitations of the Thrombolysis in Myocardial Infarction (TIMI) risk scores for use in older adults with acute myocardial infarction (AMI). Background The TIMI risk scores are risk stratification models developed to estimate mortality risk for patients hospitalized for AMI. However, these models were developed and validated in cohorts underrepresenting older adults (≥75 years). Methods Qualitative study using semi-structured telephone interviews and the constant comparative method for analysis. Results Twenty-two physicians completed interviews ranging 10–30 min (mean = 18 min). Median sample age was 37 years, with a median of 11.5 years of clinical experience. TIMI strengths included familiarity, ease of use, and validation. Limitations included a lack of risk factors relevant to older adults and model scope and influence. Conclusions Physicians report that the TIMI models, while widely used in clinical practice, have limitations when applied to older adults. New risk models are needed to guide AMI treatment in this population.
Automatic Rapid Process for the Generation of Problem-Dependent SAS2H/ORIGEN-S Cross-Section Libraries

A methodology is described that serves as an alternative to the SAS2H path of the SCALE system to generate cross sections for point-depletion calculations with the ORIGEN-S code. Automatic Rapid Pr...
On the use of mnemonics for teaching statistics

This paper is a comprehensive attempt to compile and classify mnemonics (memory aids) that can be used in statistics education.
Severe cardiovascular depression in a cat following a mandibular nerve block with bupivacaine

Abstract Observations A 12 year old cat was presented for anaesthesia to remove a mandibular squamous cell carcinoma. After intramuscular premedication with dexmedetomidine and methadone, anaesthesia was induced with alfaxalone, administered intravenously (IV) to effect, and maintained with isoflurane vaporized in oxygen, following oro-tracheal intubation. Approximately 5 minutes after performing a mandibular nerve block with 1.16 mg kg−1 of bupivacaine, the cat developed severe cardiovascular depression. Anaesthetic delivery was discontinued and cardiopulmonary resuscitation instituted. Drug administration consisted of atropine (0.02 mg kg−1 IV, repeated three times), followed by atipamezole (0.08 mg kg−1 IV). Dobutamine was subsequently administered (1 μg kg−1 minute−1 IV) until cardiovascular performance was considered satisfactory. During recovery from anaesthesia the cat exhibited seizure-like activity, which was controlled by a variable rate infusion of propofol. The cat made an uneventful recovery following discontinuation of propofol infusion, without residual neurological signs, and the surgical procedure was postponed. Conclusions This clinical report describes successful management of cardiovascular and neurological complications following a mandibular nerve block with bupivacaine in a cat. Although treatment was successful, the role played by the drugs administered during resuscitation remains uncertain.
Using Rule-Based Activity Descriptions to Evaluate Intrusion-Detection Systems

After more than a decade of development, there are now many commercial and non-commercial intrusion-detection systems (IDSes) available. However, they tend to generate false alarms at high rates while overlooking real threats. The results described in this paper have been obtained in the context of work that aims to identify means for supporting the analysis, evaluation, and design of large-scale intrusion-detection architectures. We propose a practical method for evaluating IDSes and identifying their strengths and weaknesses. Our approach shall allow us to evaluate IDSes for their capabilities, unlike existing approaches that evaluate their implementation. It is furthermore shown how the obtained knowledge can be used to analyze and evaluate an IDS.
Isolation of Acholeplasma laidlawii from Commercial, Serum-Free Tissue Culture Medium and Studies on Its Survival and Detection

This report documents the first isolation of Acholeplasma laidlawii from a commercial lot of serum-free Dulbecco basal medium. Experimental studies demonstrated survival of the organism for at least 1 year depending on the concentration of the contaminating organism as well as pH and temperature of storage of the serum-free medium. A comparison of isolation methods showed that concentration by filtration through 220-nm membrane filters and testing the filters for mycoplasma recovery, especially when using phenol red-diphasic Hayflick medium, was both sensitive and practical for the average laboratory.
K-theory and elliptic operators

This expository paper is an introductory text on topological K-theory and the Atiyah-Singer index theorem, suitable for graduate students or advanced undegraduates already possessing a background in algebraic topology. The bulk of the material presented here is distilled from Atiyah's classic "K-Theory" text, as well as his series of seminal papers "The Index of Elliptic Operators" with Singer. Additional topics include equivariant K-theory, the G-index theorem, and Bott's paper "The Index Theorem for Homogeneous Differential Operators". It also includes an appendix with a proof of Bott periodicity, as well as sketches of proofs for both the standard and equivariant versions of the K-theory Thom isomorphism theorem, in terms of the index for families of elliptic operators. A second appendix derives the Atiyah-Hirzebruch spectral sequence. This text originated as notes from a series of lectures given by the author as an undergraduate at Princeton. In its current form, the author has used it for graduate courses at the University of Oregon.
Creative Conflict in African American Thought: W. E. B. Du Bois on Religion and Art: Dynamic Contradictions and Multiple Consciousness

Of the five figures discussed in this book, Du Bois is the one most often subjected to a naive dialectic approach. His writings provide, in fact, an illustration of how the term “dialectics” can be inadequate for any study in the history of ideas, where multiple perspectives are always in opposition. He drafted a well-known dialectical passage applying the idea of internal contradiction to his own mentality, reducing himself to a double consciousness – “One ever feels this twoness – an American, a Negro; two souls; two thoughts; two unreconciled strivings; two warring ideals in one dark body, whose dogged strength alone keeps it from being torn asunder.” It is a crime that a presumably free society should ever have driven anyone to write such lines, for they cannot do justice to the complexity of any human consciousness. A sketch in black and white can be almost tactile, as we realize on those happy but rare occasions when we view a classic film projected on a real-world screen. There is nothing, in other words, artistically deficient about the monochromatic. Confinement to black and white can force upon the photographer the discipline of artificial restraint, just as confining the poet to the structure of a sonnet may test creativity and produce interesting surprises. But sketches in black and white must always be recognized as abstractions from reality, as shadows of the world.
Breast cancer screening panels continue to confuse the facts and inject their own biases

Additional confusion has been added to the “debate” about breast cancer. Women, their doctors, and the media are being misled, and women will die, unnecessarily, as a result. I recently outlined the scientific errors that I was concerned would be made by the U.S. Preventive Services Task Force (uspstf) and the International Agency for Research on Cancer (iarc) panels in their reviews of breast cancer screening guidelines1. Based on the draft proposal by the uspstf, and now iarc2, my concerns have been realized. Because the panels include few (if any) experts in screening, they are unable to sort out the validity of the various analyses involved, and they give credibility to analyses that have major flaws. One of the other major problems with the panels is that their deliberations are held in secret. If anything should be completely transparent, it should be discussions of health care guidelines. It is my understanding that the iarc panel did not unanimously agree, and that a number of panel members felt that the data supported screening women starting at the age of 40. There should be transparency, and iarc should provide full disclosure, as well as any minority reports.
An Admissibility Criterion for Fluids Exhibiting Phase Transitions

This paper shows how Korteweg’s theory of capillarity can be used as an admissibility criterion for weak solutions of the equations of compressible fluid flow. Included in the theory are fluids capable of exhibiting liquid-vapor changes of phase.
Trial watch: global migration of clinical trials.

Defining the global migration of clinical research is central to allocating resources in coordinated efforts to address global health needs. We used 15 World Health Organization-approved clinical trial registries to measure patterns of clinical research by geographic region and development over a 14-year period. With data from 205,455 trials, we show that clinical research is shifting from high-income countries to low- and middle-income Asian countries, which has clinical, public health, regulatory, ethical, and economic implications.
Photometric determination of the rate of H2O formation from H and OH in the presence of phosphine combustion products

Abstract Laser photolysis experiments are reported in which gas-phase H2O at 1960 K is photolyzed to H and OH radicals and the rate of recombination is measured. Previously, the rate of net H + OH recombination was determined by photometric measurements of OH radicals. In this article, photometric measurements at 192 nm, where H2O absorbs at elevated temperatures, are reported. When small quantities of PH3 combustion products are present in the test gas mixture, the rate of relaxation of the system to its initial state is increased substantially. A reaction model previously used to analyze OH kinetic data satisfactorily describes the time evolution of the H2O signal. These results confirm the hypothesis that phosphine combustion products open new channels for recombination of H and OH that compete with the three-body recombination reaction, H + OH + M → H2O + M.
Evidence from molecular dynamics simulations for non-metallic behaviour of solid hydrogen above 160 GPa

THE behaviour of molecular hydrogen at high pressures has implications for the interiors of the giant planets, which consist mainly of hydrogen. In particular, the question of whether solid hydrogen becomes metallic under these conditions has been much debated1–9, in part because the structure that molecular hydrogen adopts at high pressure is not known. Here we report the results of first-principles molecular dynamics simulations of solid hydrogen at pressures up to 270 GPa. We find that at 77 K, hydrogen exists as a stable, orientationally disordered phase up to 60 GPa, consistent with experimental results1,10. As the presssure is raised, a gradual transformation to an ordered orthorhombic structure begins at 160 GPa, and by 260 GPa the solid becomes semi-conducting, with an indirect band gap of 1.4eV. The calculated vibrational density of states of this phase is consistent with infrared and Raman spectra measured up to 160 GPa (ref. 11). Although limitations on the simulation time and size may result in an over-estimate of the absolute pressure, our calculations show that solid hydrogen does not become metallic, even at pressures approaching 260 GPa.
Cell volume increase and extracellular Ca2+ are needed for hyposmotically induced prolactin release in tilapia

In the tilapia (Oreochromis mossambicus), as in many euryhaline teleost fish, prolactin (PRL) plays a central role in freshwater adaptation, acting on osmoregulatory surfaces to reduce ion and wate...
After a child's parent has died.

In this preliminary study the author sought to ascertain some understanding of variability in surviving parents' and children's perceptions of family closeness, communication, and of the child's experience following the death of a parent. Data collected in interviews and from the Kvebaek Family Sculpture Test suggest that not only do parents and children differ in their expectations for and experience of communications about the parent's death but they also differ in their levels of felt closeness in the family, a situation which might markedly affect the child's subsequent emotional development.
Absolute calibration of flow calorimeters used for measuring differences in heat capacities. A chemical standard for temperatures between 325 and 600K

Two methods for the absolute calibration of flow calorimeters (used for measuring the differences in heat capacities of two fluids) have been investigated. In the recommended method of calibration, a change in the flow rate of the fluids is used to minic a change in the heat capacity of the fluid. In the other method of calibration, heat loss is measured using a fluid of known heat capacity, and it is assumed this heat loss is constant. This calibration method is not recommended because the heat loss is, in general, not constant. For some calorimeters the difference between the two methods of calibration is negligible, while for others erros as high as 40% are caused by choosing the wrong method. A detailed analysis of the heat losses in this kind of calorimetry shows why the two calibration methods give different results and leads to various methods of improving calorimeter construction and operation. Because chemical standardization is far more convenient for routine use, the recommended absolute calibration method has been used to establish 3.00 mol-kg−1 aqueous NaCl as a chemical standard for temperatures between 325 and 600K at 17.7 MPa.
Highly nonlinear waves' sensor technology for highway infrastructures

This paper describes preliminary results towards the development of an innovative NDE/SHM scheme for material characterization and defect detection based on the generation of highly nonlinear solitary waves (HNSWs). HNSWs are stress waves that can form and travel in highly nonlinear systems (i.e. granular, layered, fibrous or porous materials) with a finite spatial dimension independent on the wave amplitude. Compared to conventional linear waves, the generation of HNSWs does not rely on the use of electronic equipment (such as an arbitrary function generator) and on the response of piezoelectric crystals or other transduction mechanism. HNSWs possess unique tunable properties that provide a complete control over tailoring: 1) the choice of the wave's width (spatial size) for defects investigation, 2) the composition of the excited train of waves (i.e. number and separation of the waves used for testing), and 3) their amplitude and velocity. HNSWs are excited onto concrete samples and steel rebar. The first pilot study of this ongoing effort between Caltech and the University of Pittsburgh is presented.
GABA and GABA-A receptors are maximally expressed in association with cone synaptogenesis in neonatal rabbit retina

Previous studies have shown the cone photoreceptors form reciprocal synapses with horizontal cells during the first week after birth in rabbits. These synapses constitute pioneering elements of the developing outer plexiform layer. We now report that antibodies against the alpha-1 and against the beta-2/3 subunits of the GABA-A receptor label a highly restricted sublamina in the developing outer plexiform layer known to contain nascent cone photoreceptor terminals. Staining is relatively weak at birth, increases to maximal levels between postnatal days 5 and 7, and is significantly reduced in the adult. These results support recent calcium imaging studies which have shown that the activation of GABA-A receptors causes an increase in intracellular free calcium in cones, an effect which is observed only at 3-9 days after birth. The transient expression of GABA-A receptors in this region coincides with the period of peak expression of GABA immunoreactivity in horizontal cells. A direct functional link between GABAergic transmission and cone synaptogenesis is suggested by previous reports that GABA-A receptor antagonists cause disruption of cone synaptogenesis. Together these findings support the notion that GABA functions as a developmental neurotransmitter which is produced by horizontal cells and interacts with developing cone axons in order to facilitate synaptic linkage between these two cells types.