cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of GABRA1 Cytoplasmic Peptide on a Regulatory Protein

The pentameric neurotransmitter-gated chloride channel, GABA (type A) receptor, is well-recognized for phasic and tonic neuronal inhibition. The phasic response at the synapse is due to receptors typically containing two alpha, two beta, and one gamma subunit. Half of all GABA (type A) receptors in adult human brain have the alpha (type 1), or alpha-1, subunit (gene ID: GABRA1). Each consists of an extracellular ligand-binding domain and four transmembrane helices (TM1-4), both of which are highly conserved, as well as a large intracellular loop domain (ILD), whose structure is unknown. The human receptor is crystallized without the ILD, which connects TM3 and TM4, that is engineered out. The topology and function of the 86-residue alpha-1 ILD remains to be fully elucidated. GAPDH (d-glyceraldehyde-3-phosphate dehydrogenase) phosphorylates specific ILD residues, regulating receptor function. In this study, we examined the effect of a synthesized ILD peptide (residues 335 to 364 from GABRA1) on the oxidoreductase activity of GAPDH. The custom peptide, containing the first 30 cytosolic residues, was pre-incubated with GAPDH, and enzyme activity measured by NADH absorbance (340nm) upon oxidation of the substrate d-glyceraldehyde. When pre-incubated for 1hr at 20degC, the ILD peptide inhibited enzyme activity in a concentration-dependent manner showing an exponential non-linear function (y=a∗e ˆ (b/x+c)). The half-maximum inhibition occurred at a [peptide] = 8.7micromolar. When pre-incubated for 48hr at 4degC, the ILD peptide further enhanced inhibition of oxidoreductase activity, suggesting that hydrophobic forces play a role in the interaction between the ILD peptide and GAPDH. Molecular modeling experiments indicate that the ILD binding site on GAPDH is in close proximity to the phosphatidylserine-binding site on GAPDH. The findings may contribute to our understanding of receptor function and point to possible treatments in conditions, such as Alzheimer's dementia, where GABA receptor pharmacology is shown to play a role.
Barriers to Genetic Testing for Pediatric Medicaid Beneficiaries With Epilepsy

Abstract Background Children with public insurance (Medicaid) have increased barriers to specialty care in the United States. For children with epilepsy, the relationship between public insurance and barriers to genetic testing is understudied. Methods We surveyed a sample of US child neurology clinicians. We performed quantitative and qualitative analysis of responses. Results There were 302 responses (of 1982 surveyed; response rate 15%) from clinicians from 46 states, the District of Columbia, and Puerto Rico, including board-certified child neurologists (82%), resident physicians (6%), nurses (3%), and nurse practitioners (3%). Clinicians felt it was more difficult to get genetic testing for patients with Medicaid insurance compared with commercial insurance, (43% vs 12%, P P P P Conclusions Pediatric Medicaid beneficiaries with epilepsy have barriers to genetic testing, compared with children with commercial insurance, particularly for more advanced testing. Potential strategies to improve access include broader coverage, lower co-pays, increased capacity for testing outside of specialty laboratories, fewer preauthorization requirements, improved clinician education, ongoing development and dissemination of guidelines, improved availability of clinical genetics services, and continued assistance programs from commercial laboratories.
Evaluating the knowledge base and current training of paramedics in the southwest United States in assessing and managing toxic alcohol exposures

Introduction: The aim of this research was to use a survey to identify the cognitive capabilities of paramedics to recognize key clinical, pathophysiological and treatment features of toxic alcohol poisoning. Additionally, evaluation of affective capabilities of paramedics in terms of the level of importance paramedics assign to toxic alcohol emergencies was evaluated. Methods: The study was conducted as an anonymous online survey. Demographic data, timed choice, and open-ended questions were collected to evaluate knowledge and identify gaps in toxic alcohol poisoning training by paramedics. The survey link was sent out to EMS organizations and individual paramedics. Bivariate analysis via Pearson correlation coefficient (PCC) was used to compare variables. Results: The response rate was 72.5% (58/80). Respondents were able to identify common sources of toxic alcohol exposure to varying degrees with 58% for methanol and 89% for ethylene glycol. Data indicate that a lack of understanding of the underlying pathophysiology was related to missing education (PCC <0.05) in toxicology. Education appears to be insufficient in regards to recognizing and treating toxic alcohol exposure. A majority of respondents (80%) believe that assessment and treatment of toxic alcohol poisoning is an important component of their training. Conclusions: Although symptom recognition for toxic alcohol poisoning is present in most EMS providers, pharmacological intervention and treatment approaches are often not known. The results indicate that there is a need for educators and curriculum builders to include additional coverage of topics of toxicological importance such as the anion gap and toxic alcohol assessment, pathophysiology and treatment.
The lunar environment

A primary source for the physical and chemical properties of the Moon and its environment was written and edited by Heiken et al. [1]. The lunar physical environment is dramatically different than that of the Earth [2, 3]. Human health risks are continually studied and updated with new data [4]. A summary of lunar physical parameters is presented in Table 3.1.
Can the Effect of Continuing Medical Education on Physician Performance Be Measured

The development, description, and implementation of continuing medical education programs that utilize patient outcome measures were studied. The Practice Integrated Learning Sequence (PILS) described consists of three essential features. They are: needs assessment, the educational prescription, and application to medical practice by means of a patient report form which can evaluate the effectiveness of the process. The process has been applied to the following clinical problems: Management of hypertension by a single beta blocker, management of refractory congestive heart failure by a single Angiotensin Converting Enzyme inhibitor, drug prescribing for the elderly, management of atrial fibrillation in a primary care setting, and malpractice prevention. This process can be used by practically all CME providers and is not intrusive on medical practice.
Structural and Functional Evolution of Resynthesized Polyploids

Polyploidy is widespread among the flowering plants. While many extant plant species show evidence of polyploidy in their genomes, there is still much to be learned regarding the role it has played in phenotypic evolution and speciation. The Brassica genus has polyploidy at multiple levels: the genomes of diploid species show evidence of repeated rounds of ancient polyploidization, and the agronomically important diploid species (Brassica rapa, Brassica oleracea, and Brassica nigra) may hybridize to form allopolyploids (Brassica napus, Brassica juncea, and Brassica carinata). The phenotypic diversity among these six domesticated species is spectacular. Research has provided evidence that gene and genome redundancy contribute significantly to the variation observed among Brassica species. The relative ease by which Brassica allopolyploids can be resynthesized has allowed them to emerge as an efficient model for studying the consequences of polyploidization. Studies on resynthesized B. napus polyploids have reported on homoeologous genome rearrangements and epigenetic changes, as well as changes in gene expression, protein expression, and phenotypic variation in the early generations following hybridization and polyploidization. In contrast, studies in resynthesized B. juncea polyploids show little evidence for rapid changes, although a recent report indicated changes within the organelle genomes. The differences between these two resynthesized allopolyploids may be attributed to the differing degrees of similarity between their diploid progenitor genomes (those of B. napus being more similar to each other than those of B. juncea). It may also be due to differences in genetic variation for homoeologous pairing control in these two species. These studies demonstrate that polyploidization may have immediate genetic and phenotypic consequences, particularly in B. napus. The variation that results from a polyploidization event may be critical in the early establishment and evolution of new polyploids; however, selection must have played a critical role in the establishment of natural Brassica polyploids, as their genomes appear relatively stable. Future studies of resynthesized Brassica allopolyploids should include tests for the effects of progenitor genotypes, selection for fertility under field-style conditions, and use genomic approaches that have up to now been limited to studies of polyploid Arabidopsis suecica.
Interactive Event: The Rimac Tutor - A Simulation of the Highly Interactive Nature of Human Tutorial Dialogue

Rimac is a natural-language intelligent tutoring system that engages students in dialogues that address physics concepts and principles, after they have solved quantitative physics problems. Much research has been devoted to identifying features of tutorial dialogue that can explain its effectiveness (e.g., [1]), so that these features can be simulated in natural-language tutoring systems. One hypothesis is that the highly interactive nature of tutoring itself promotes learning. Several studies indicate that our understanding of interactivty needs refinement because it cannot be defined simply by the amount of interaction nor the granularity of the interaction but must also take into consideration how well the interaction is carried out (e.g., [2]).
Structure of Symmetric Domains

We continue with the setup and notations of Chapter III. For each \( \gamma \in \Gamma \) we set $$ {c_\gamma } = \exp \frac{\pi }{4}i{x_\gamma } $$ (4.1.1) we also write C j when γ= γ j . We also use the abbreviation $$ xr = \sum\limits_{r \in \Gamma } {{x_\gamma }} $$ and, similarly, yΓ, eΓ, etc. We set $$ c = {c_1}...{c_r} = \exp \frac{\pi }{4}ix\Gamma $$ (4.1.2)
Rescue therapies for seizure emergencies: New modes of administration.

A subgroup of patients with drug-resistant epilepsy have seizure clusters, which are a part of the continuum of seizure emergencies that includes prolonged episodes and status epilepticus. When the patient or caregiver can identify the beginning of a cluster, the condition is amenable to certain treatments, an approach known as rescue therapy. Intravenous drug administration offers the fastest onset of action, but this route is usually not an option because most seizure clusters occur outside of a medical facility. Alternate routes of administration have been used or are proposed including rectal, buccal, intrapulmonary, subcutaneous, intramuscular, and intranasal. The objective of this narrative review is to describe the (1) anatomical, physiologic, and drug physicochemical properties that need to be considered when developing therapies for seizure emergencies and (2) products currently in development. New therapies must consider parameters of Fick's law such as absorptive surface area, blood flow, membrane thickness, and lipid solubility, because these factors affect both rate and extend of absorption. For example, the lung has a 50 000-fold greater absorptive surface area than that associated with a subcutaneous injection. Lipid solubility is a physicochemical property that influences the absorption rate of small molecule drugs. Among drugs currently used or under development for rescue therapy, allopregnanolone has the greatest lipid solubility at physiologic pH, followed by propofol, midazolam, diazepam, lorazepam, alprazolam, and brivaracetam. However, greater lipid solubility correlates with lower water solubility, complicating formulation of rescue therapies. One approach to overcoming poor aqueous solubility involves the use of a water-soluble prodrug coadministered with a converting enzyme, which is being explored for the intranasal delivery of diazepam. With advances in seizure prediction technology and the development of drug delivery systems that provide rapid onset of effect, rescue therapies may prevent the occurrence of seizures, thus greatly improving the management of epilepsy.
Paget’s Disease of Bone

Paget’s disease is a common disease of the bone, second in prevalence to osteoporosis. We review the epidemiology and prevalence of this disease, focusing on regional and temporal differences. The pathogenesis and genetic aspects are discussed. Clinical features are enumerated. Diagnosis is outlined. Therapy is reviewed.
Fibrous Dysplasia of Bone and McCune-Albright Syndrome: A Bench to Bedside Review.

Fibrous dysplasia is an uncommon mosaic disorder in which bone is replaced by structurally unsound fibro-osseous tissue. It is caused by the sporadic post-zygotic activating mutations in GNAS, resulting in dysregulated GαS-protein signaling in affected tissues. This manifests on a broad clinical spectrum ranging from insignificant solitary lesions to severe disease with deformities, fractures, functional impairment, and pain. Fibrous dysplasia may present in isolation or in association with hyperfunctioning endocrinopathies and cafe-au-lait macules, known as McCune–Albright Syndrome. This review summarizes the current understanding of pathophysiology in fibrous dysplasia, describes key pre-clinical and clinical investigations, and details the current approach to diagnosis and management.
Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia by Inhibition of Ca 2+ /Calmodulin-Dependent Kinase II.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited cardiac arrhythmia characterized by adrenergically triggered arrhythmias, is inadequately treated by current s...
CIMAT: a transpose SRAM-based compute-in-memory architecture for deep neural network on-chip training

Rapid development in deep neural networks (DNNs) is enabling many intelligent applications. However, on-chip training of DNNs is challenging due to the extensive computation and memory bandwidth requirements. To solve the bottleneck of the memory wall problem, compute-in-memory (CIM) approach exploits the analog computation along the bit line of the memory array thus significantly speeds up the vector-matrix multiplications. So far, most of the CIM based prototype chips target at implementing inference engine for offline training only. In this work, we design the data flow for the backpropagation (BP) process and weight update to support the on-chip training based on CIM. We utilize the mature and advanced CMOS technology at 7 nm to design the CIM architecture with 7T transpose SRAM array that supports bidirectional parallel read. We explore the 8-bit training performance of ImageNet on ResNet-18 using this CIM architecture for training, namely CIMAT, showing that it can achieve 3.38× higher energy efficiency (~6.02 TOPS/W), 4.34× frame rate (~4,020 fps) and only 50% chip size compared to the baseline architecture with conventional 6T SRAM array that supports row-by-row read only.
Chronic pain, cardiovascular health and related medication use in ageing African Americans with osteoarthritis.

Aim and objectives To describe the (a) prevalence and perceptions of cardiovascular disease and related health conditions in African Americans with osteoarthritis pain, (b) their knowledge of cardiovascular safety of commonly prescribed analgesics for osteoarthritis and (c) frequency of high-risk analgesic use. Background African Americans have more disabling osteoarthritis pain and an excessive burden of cardiovascular disease than any other US racial group. However, minimal research has investigated the relationship between chronic pain and cardiovascular disease and subsequent medication knowledge and use in African Americans. Consolidated Criteria for Reporting Qualitative and Srengthening the Reporting of Observational studies in Epidemiology checklists were followed. Design A descriptive, secondary mixed-methods analysis. Methods A convenience sample of 110 African American adults (50-94 years and older) completed surveys and individual qualitative interviews. Data were analysed using descriptive statistics, chi-square or Fisher's exact test, t test, Mann-Whitney U and a qualitative content analysis. Results Hypertension was the most common cardiovascular condition reported, and African Americans with hypertension reported greater pain than those without. The survey questions revealed that most participants did not possess accurate knowledge about the appropriateness of analgesics in heart failure and other cardiovascular-related diseases; however, during the interviews, some did acknowledge a general understanding of the negative effects of some medications. Still, many older adults were taking nonsteroidal anti-inflammatory drugs despite having hypertension. Conclusions There was evidence of multimorbidity in our sample; based on our data, chronic osteoarthritis pain and hypertension are two highly comorbid conditions, suggesting a possible syndemic. More disparate is the lack of knowledge that African Americans possess as it relates to safe use of analgesic medications when cardiovascular disease is present. Relevance to clinical practice Chronic pain and cardiovascular-related diseases are common and often co-occur and should be evaluated in all older adults, particularly African Americans. Both issues are important to manage, including the safe and appropriate use of medications, to prevent adverse effects.
Thermal behavior of AZ31 gradient microstructure after cold severe surface plastic deformation

Abstract Surface severe plastic deformation such as severe shot peening has been proposed to manufacture a gradient microstructure with grains smaller than 5 μm near the surface. Subsequent annealing of the heavily cold deformed structure contributes to grain boundary recovery, dislocation rearrangement or annihilation, and consequently ductility enhancement due to the formation of defect-free grains. This structure would be unstable in thermal conditions due to incomplete recrystallization, high density of dislocations, and smaller grain size. In this work, microstructural evolution and thermal stability of a gradient microstructure created via the severe shot peening process in AZ31 is investigated through characterizing the microstructure during isothermal and isochronal heat treatment. In the end, thermal stability of the structure is demonstrated wherein recrystallization started at 150 ∘C from the surface and continued through the thickness until new defect-free grains appeared in all deformed layers. The newly-formed structure stays relatively stable with slow grain growth from temperature 300 ∘C to 450 ∘C that leads to the acceptable value of grain boundary activation energy.
Inequality and Economic Stratification: Reflections on Bromley, Piketty, and Obeng-Odoom

The rise of economic inequality is a major global problem, one that economists have an important role in explaining and addressing through policy. Despite increased availability of data, our theore...
Nonlinear self-trapping and guiding of light at different wavelengths with sheep blood

We demonstrate the formation of waveguides, a few centimeters long, in colloidal suspensions of sheep red blood cells for a wide range of wavelengths due to nonlinear self-trapping and self-guiding of a laser beam. The near infrared (NIR) light experiences a weaker nonlinear self-action and thus requires much higher power to obtain self-trapping as compared to visible light. To examine the waveguiding of light at different wavelengths, we utilize a pump–probe-type setting for beam coupling: a pump beam at a 532 nm wavelength is used to create a waveguide first, and then a probe beam with various wavelengths is sent through the waveguide channel. Effective guidance for both visible and NIR wavelengths is observed through such otherwise highly scattering bio-soft-matter.
Cerebrospinal Fluid Immunoelectrophoretic Findings in Multiple Sclerosis

In 1962, Laterre et al.,[1] and later Dencker[2] reported the presence of a second precipitation arc, in a parallel position to the precipitate of immunoglobulin G (IgG), in cerebrospinal fluid (CSF) Immunoelectrophoresis (IE) of some patients with multiple sclerosis (MS). This doubling of the CSF IgG precipitate was not demonstrated in the corresponding serum specimens. It was later indicated by Laterre et al.,[3] that the duplication of the CSF IgG precipitate in certain CSF specimens of MS patients is due to an imbalance in the CSF K/λ light chain ratio.
The History of Perinatal Psychiatry

The establishment of perinatal psychiatry as a specialty field can be traced to the 1980s and the inception of the Marce Society in the United Kingdom. Inspired by the works of nineteenth-century French psychiatrist Louis-Victor Marce, the Marce Society launched 50 subsequent years of progress towards improving research, clinical treatment and education surrounding perinatal mood disorders. The Marce Society and other organizations like Postpartum Support International have created a global community of researchers, clinicians, educators and patient advocates dedicated to improving outcomes for patients and families experiencing perinatal mood disorders. Utilizing a cadre of innovative care solutions including specialized mother-baby units, a new medication specifically for postpartum depression and advancements in care delivery like telemedicine, perinatal psychiatry has emerged from its forgotten past into the twenty-first century.
Clinical Redeployment of an Academic Family Medicine Department in an Early, Severe COVID-19 Pandemic in the Bronx, NY.

Introduction: A severe surge of the COVID-19 pandemic in spring 2020 infected 33% of the population and caused more than 7000 deaths in the Bronx, NY. The Department of Family and Social Medicine at Montefiore Medical Center rapidly and strategically reconfigured clinical services to meet the needs of patients, communities, and the health system. Clinical Reconfiguration: Family medicine hospitalist services tripled in size within 2 weeks to cover 71 beds and cared for 447 patients between March 24 and June 10, 2020, of whom 279 (62.4%) had COVID-19. Community health centers reorganized to maintain primary care services, shifting abruptly to telemedicine while maintaining 95% of the previous year9s visit volume, and address intensified patient needs related to viral infection and mental health impacts. Core principles for redeployment included role flexibility, communication, responsiveness, and safety and wellness. Discussion: During a pandemic surge, academic family medicine departments have an important role in expanding hospitalist services and redesigning primary care services. The ability to reconfigure work to meet unprecedented demands on health care was facilitated by family medicine9s broad scope of practice including training in hospital medicine, interpersonal communication, behavioral health, care across settings, collaborative partnerships with specialists, and adaptability to communities9 needs.
The Hyphy Discourse (2000–2010)

This chapter shows that the hyphy brand of music remained strikingly distinct from other contemporary waves and better retained its political, radical, and militant edge while also gaining popularity and commercial appeal. Rapper Mac Dre and others harnessed the hyphy style of music, which originated as a reaction to state power. Hyphy evolved from earlier local rap styles, which were themselves influenced by the late 1960s Black militant and socialist counterculture. Hyphy came to define a style of music with up-tempo beats, filled with Bay Area-developed lingo, and containing messages aimed at the subversion of public space. After the music and subculture were partially adopted by the mainstream, some local artists began to form a highly pronounced reaction against hyphy by using its style but reforming the messages to highlight the violence, economic conditions, and social turmoil in the locale.
Enhanced work hardening from oxygen-stabilized ω precipitates in an aged metastable β Ti-Nb alloy

Abstract High levels of oxygen in solid solution in Ti alloys are considered detrimental to mechanical properties because of embrittlement concerns. In metastable β titanium alloys, the formation of isothermal ω precipitates is also known to cause severe embrittlement and ductility reduction. However, oxygen has been shown to partition to the ω phase during ageing, and this partitioning behavior may potentially impact ω’s mechanical contribution. Using micropillar compression, we compared the deformation behavior of Ti-20Nb (at. %) with oxygen-stabilized ω precipitates to the behavior of oxygen-free specimens. The oxygen-stabilized microstructures showed increased compressive yield strength and enhanced work hardening behavior compared to oxygen-free specimens. In the absence of oxygen, the compressed pillars showed slip band formation and catastrophic failure, and transmission electron microscopy imaging revealed that ω precipitates were sheared within the continuous deformation channels resulting in slip localization. In contrast, oxygen-stabilized ω precipitates were harder to shear and the formation of continuous deformation channels was suppressed during compression, leading to improved work hardening behavior up to 15% strain. This counter-intuitive role of oxygen may offer design strategies to address the significant embrittlement and loss of ductility observed for ω-strengthened β Ti alloys without oxygen and avenues to expand the use of β Ti alloys.
Experimental Investigations of the Relationship of Baseball Bat Properties on Batted-Ball Performance

Laboratory tests are used to investigate the relationship between baseball bat performance and two bat properties: moment of inertia (MOI) and barrel stiffness for aluminum and composite bats. Each bat used in the current study is specifically designed and manufactured to isolate a particular property. Static tests, e.g. three-point bend and barrel compression, are used to characterize the properties of each bat. The natural frequencies of the bat are measured using modal techniques. Dynamic performance testing is done using an air cannon capable of throwing a baseball at collision speeds equal to those seen in field play. For the bats studied, variation in MOI contributed more to performance in the lab than did barrel stiffness. However, the changes in predicted field performance due to the two properties were similar.
Use of a viral probe to study recombinational exchanges in mammalian cells.

Publisher Summary This chapter uses viral probe to study recombinational exchanges in mammalian cells. The approach to probing mammalian cell recombination involves the superinfection of an Ad2-transformed cell line with Ad5. Recombinational events can be detected in progeny DNA if Ad5 DNA, which contains only one endodeoxyribonuclease Bam HI recognition site, acquires additional Bam HI recognition sites from the integrated Ad2 genomic fragment. These additional sites are derived from the Bam HI sites at map positions 29 and 42 of the Ad2 genomic fragment. The viral genomic fragment integrated within the F4 cell line contains 16 copies of Ad2 DNA sequences arranged as follows: an inverted right-hand fragment is joined to the left 63% (approximately) of the Ad 2 genome near map position 0. The F4 cell line does not contain free viral DNA. In experiments to determine whether ultraviolet photoproducts modulate recombination, Ad5 was irradiated prior to infection and the progeny virus DNA was analyzed. Studies indicate that adenovirus type 5 DNA undergoes recombinational exchanges with the adenovirus type 2 sequences integrated within the F4 cell line. UV irradiation of Ad5 prior to infection of F4 appears to modulate these recombinational events. These recombinational exchanges result in the appearance of Ad2 Bam HI-B, -C, and -D size restriction fragments in the progeny virus recovered from the infection of F4 cells with Ad5.
A Study of the Factors and Conditions Associated with Graduate Enrollment Management Practitioners’ Participation in Professional Development

This investigation was designed to determine the factors and conditions associated with graduate enrollment management practitioners’ participation in professional development (PD) activities. The sample consisted of members of a professional association, the National Association of Graduate Admissions Professionals (NAGAP), focused solely on supporting graduate enrollment managers and related staff, whose patterns of involvement in various PD events for the previous five years were classified as low or inconsistent. In an effort to identify member preferences, as well as characteristics associated with PD activities, the investigator sought to provide information useful to developing future PD programs for NAGAP. An electronic quantitative instrument, the Professional Development in Graduate Enrollment Management (PDGEM) survey, consisted of closed-ended questions related to PD grouped under the following headings: Demographic Information, Support for and Knowledge of Professional Development Activities, Attitudes and Beliefs about Professional Development: Individual and Institutional, Components of Professional Development in Graduate Enrollment Management, Professional Development Plans, Participation and Involvement in NAGAP Professional Development Activities, Other Organizations’ Professional Development, and Professional Development Overall. It was disseminated to 1,461 members of NAGAP, with a return rate of 163 (11%). Descriptive and linear regression analyses were conducted in order to discern (1) the frequency of participation in PD and (2) the demographic and other variables predictive of participation in PD. The study's findings revealed that about one-quarter of the respondents participated regularly in NAGAP-sponsored PD and that the involvement levels of the remainder of the membership were inconsistent. Additionally, on-site activities were favored over online, content relevance greatly influenced whether practitioners participated, and member interest in conducting academic research was low. Cost was also a primary factor in determining participation in professional development.
P2Y1 purinoreceptors are fundamental to inhibitory motor control of murine colonic excitability and transit

Activation of enteric inhibitory motor neurons causes inhibitory junctional potentials (IJPs) and muscle relaxation in mammalian gastrointestinal (GI) muscles, including humans. IJPs in many GI muscles are bi-phasic with a fast initial hyperpolarization (fIJP) due to release of a purine neurotransmitter and a slower hyperpolarization component (sIJP) due to release of nitric oxide. We sought to characterize the nature of the post-junctional receptor(s) involved in transducing purinergic neural inputs in the murine colon using mice with genetically deactivated P2ry1. Wild-type mice had characteristic biphasic IJPs and pharmacological dissection confirmed that the fIJP was purinergic and the sIJP was nitrergic. The fIJP was completely absent in P2ry1−/− mice and the P2Y1 receptor antagonist MRS2500 had no effect on electrical activity or responses to electrical field stimulation of intrinsic nerves in these mice. Contractile experiments confirmed that purinergic responses were abolished in P2ry1−/− mice. Picospritzing of neurotransmitter candidates (ATP and its primary metabolite, ADP) and β-NAD (and its primary metabolite, ADP-ribose, ADPR) caused transient hyperpolarization responses in wild-type colons, but responses to β-NAD and ADPR were completely abolished in P2ry1−/− mice. Hyperpolarization and relaxation responses to ATP and ADP were retained in colons of P2ry1−/− mice. Video imaging revealed that transit of fecal pellets was significantly delayed in colons from P2ry1−/− mice. These data demonstrate the importance of purinergic neurotransmission in regulating colonic motility and confirm pharmacological experiments suggesting that purinergic neurotransmission is mediated via P2Y1 receptors.
Decreased gene expression from T7 promoters may be due to impaired production of active T7 RNA polymerase

Background Protein expression vectors that utilize the bacteriophage T7 polymerase/promoter system are capable of very high levels of protein production. Frequently, however, expression from these vectors does not reliably achieve optimal levels of protein production. Strategies have been proposed previously that successfully maintain high expression levels, however we sought to determine the cause of induction failure.
A Measure of Adolescent Potential for Suicide (MAPS): Development and Preliminary Findings

This paper describes an instrument designed to assess the suicide potential of youth 14-18 years of age who are at risk for suicidal behaviors. A comprehensive measurement theory provides the basis for three central constructs in the Measure of Adolescent Potential for Suicide (MAPS): direct suicide risk factors, related risk factors, and protective factors. The MAPS entails an introductory questionnaire followed by a computer-assisted, structured interview. Two samples were used to examine psychometric properties of the MAPS (n = 43; n = 123). Results revealed generally strong validity (content, criterion, construct) and reliability (internal consistency) for the MAPS. Further verification studies with large and diverse samples are warranted.
Advances in stroke management.

Traditionally, leukocytes of normal function are considered a vital blood element without which the body's survival would be threatened. Leukocytes protect us from invading microorganisms. Without them, we would easily fall prey to the life-threatening attack of otherwise benign infections. In the past few years we have come to realize that as leukocytes react to a variety of tissue injuries, including ischemia, they may actually contribute to and accentuate tissue damage. When tissue injuries such as ischemia occur, signals arise in the endothelium of the microvasculature in the ischemic brain to attract leukocytes to the region of injury. Leukocytes in the circulating blood pass by the vasculature of ischemic brain. They are compelled to linger and attach to the endothelium, flatten, and penetrate the endothelium into the injured ischemic tissue. We now know that there are a variety of receptors on the leukocyte surface that have the ability to react to receptor sites on the endothelium. Among these receptors is the intercellular adhesion molecule-1 (ICAM-1) located on the endothelial cells. Leukocyte adhesion and migration require the interaction of ICAM-1 on the endothelium with CD11/CD18 leukocyte integrins on the surface of neutrophils. As leukocytes and monocytes adhere to the vessel wall, they can release damaging cytokines including IL-1, IL-2, and tissue necrosis factor alpha(TNF-α). These cytokines become proinflammatory and can promote thrombosis by binding circulating anticoagulants, such as protein S, and inhibiting tissue plasminogen activator release. Some of the early basic observations that led to an understanding of this process grew out of the …
Documenting information systems for management: a key to maintaining user satisfaction

Abstract Executives responsible for the information system function need to be concerned about developing a base of satisfied users and maintaining continuing user satisfaction after implementation. This article focuses on user satisfaction among on-going user manager, explores the role of good user documentation, and examines the results of a survey of 144 user managers from 55 firms. The results indicate that good user documentation appears to be an important factor in insuring user understanding and continuing user satisfaction. Thus firms considering alternative ways of keeping users satisfied (i.e., personal computer applications, end user computing, or information centers) might well examine their user documentation practices before exploring other alternatives.
Topical Cardiac Hypothermia and Phrenic Nerve Injury

The relationship between ice-chip cardioplegia and impaired left diaphragmatic function was evaluated in dogs. Direct or indirect contact of the phrenic nerve with crushed ice for 30 or 60 minutes resulted in phrenic paralysis for 6 to 28 days, with responsiveness returning from 7 to 62 days later. Microscopical examination of injured nerves revealed injury to the myelin sheath and preservation of axons. Paralysis of the left diaphragm after topical cardiac hypothermia may be secondary to cold injury of the phrenic nerve, which is reversible.
Trisomy 4 as the sole cytogenetic abnormality in a Waldenström macroglobulinemia

We report a case of Waldenstrom macroglobulinemia with trisomy 4 as the sole cytogenetic abnormality. Trisomy 4 has been reported previously in Waldenstrom macroglobulinemia, but only in conjunction with multiple chromosomal aberrations. Trisomy 4 has been reported in other hematologic malignancies including acute myeloid and lymphoid leukemias.
Relationship between Thyrotropin Receptor Hinge Region Proteolytic Posttranslational Modification and Receptor Physiological Function

The glycoprotein hormone receptor hinge region is the least conserved component and the most variable in size; the TSH receptor (TSHR) being the longest (152 amino acids; residues 261–412). The TSHR is also unique among the glycoprotein hormone receptor in undergoing in vivo intramolecular cleavage into disulfide-linked A- and B-subunits with removal of an intervening ‘C-peptide’ region. Experimentally, hinge region amino acids 317–366 (50 residues) can be deleted without alteration in receptor function. However, in vivo, more than 50 amino acids are deleted during TSHR intramolecular cleavage; furthermore, the boundaries of this deleted region are ragged and poorly defined. Studies to determine the extent to which hinge region deletions can be tolerated without affecting receptor function (‘minimal hinge’) are lacking. Using as a template the functionally normal TSHR with residues 317–366 deleted, progressive downstream extension of deletions revealed residue 371 to be the limit compatible with normal TSH binding and coupling with cAMP signal transduction. Based on the foregoing downstream limit, upstream deletion from residue 307 (307–371 deletion) was also tolerated without functional alteration, as was deletion of residues 303–366. Addressing a related issue regarding the functional role of the TSHR hinge region, we observed that downstream hinge residues 377–384 contribute to coupling ligand binding with cAMP signal transduction. In summary, we report the first evaluation of TSHR function in relation to proteolytic posttranslational hinge region modifications. Deletion of TSHR hinge amino acids 303–366 (64 residues) or 307–371 (65 residues) are the maximum hinge region deletions compatible with normal TSHR function.
Grievances against physicians: 11 years' experience of a medical society grievance committee.

OBJECTIVE To understand causes of patient dissatisfaction that result in complaints. DESIGN Grievances received by the grievance committee between January 1, 1989, and January 1, 2000, were reviewed. SETTING A 2-county area of North Carolina. SUBJECTS Of 29 patients who filed grievances, the 9 male (31%) and 20 female (69%) patients had a mean (+/-SD) age of 39 (+/-19) years. In 18 instances, the patient consulted the physician less than 3 times (64%) before the complaint and in 8 instances more than 4 times (29%). Main outcome measures Allegations of the grievance and the committee's findings. RESULTS Grievances fell into 5 categories: failure to fulfill expectations for examination and treatment (38%), failure to promptly diagnose (20%), rudeness (17%), producing excessive pain or practicing beyond the area of expertise (13%), and inappropriate behavior related to billings (10%). In 45% of the grievances, the committee found no breach of practice standards. In 17% of the cases, the physician resolved the grievance by apologizing, adjusting a bill, or completing insurance forms. CONCLUSION Most grievances were filed by younger women against newly encountered physicians and were related to inadequate communication or alleged delay in diagnosis.
On the Name(s) of the Prostaja Mova in the Polish-Lithuanian Commonwealth

A variety of names are traditionally used to refer to the literary language as cultivated by the Belarusians and Ukrainians in the late Middle Ages. It is maintained that the emergence of the term prostaja mova/prostyj jazykъ was brought about by the (German) Reformation in the Polish Kingdom and the Grand Duchy of Lithuania. Based on a comparative analysis of the names of the prostaja mova attested in Ruthenian, Polish, and Lithuanian writings, the author surmises that the coinage and the use of the corresponding terms was primarily determined by the revival of the indigenous “linguistic democratism” dating back to the time of Constantine and Methodius.
Faith and Values: Journalism and the Critique of Religion Coverage of the 1990s

This article explores whether changes in newspaper coverage of religion reflect an array of concerns that were raised in the 1990s. It seeks to establish a baseline of what groups are portrayed in staff-written articles carried on religion pages and finds that some changes reflect critics' concerns while others might appear to amplify them. Of particular interest is the growth of instrumental “values” coverage with little or no overt connection to the religious precepts that underlie its topics.
Acoustic emission and crack propagation in polycrystalline alumina

Abstract Acoustic emission is measured during the fracture of polycrystalline alumina. It is shown that acoustic emission is obtained during macrocrack growth, which can be used for failure indication. Acoustic emission is also obtained owing to the formation of non-propagating grain size microcracks at the surface. This emission can mask that due to macrocrack growth, but only for short failure times or at high stresses. Models are presented which relate the acoustic emission to the various crack propagation processes.
Use of chrome azurol S reagents to evaluate siderophore production by rhizosphere bacteria

Siderophores produced by rhizosphere bacteria may enhance plant growth by increasing the availability of Fe near the root or by inhibiting the colonization of roots by plant pathogens or other harmful bacteria. To examine the populations of siderophore-producing bacteria colonizing the roots of two grass species that differed in their susceptibility to Fe deficiency, we inoculated serial dilutions of root samples onto chrome azurol S (CAS) agar and several other selective and non-selective culture meida. CAS agar effectively differentiated bacteria that were capable of excreting large amounts of siderophore, but the composition of the medium limited its usefulness for ecological studies. A large proportion (71–79%) of the bacterial population that grew on a non-selective medium (tryptic soy agar) failed to grow on CAS agar, and several isolates that showed no sign of siderophore production on CAS agar produced siderophore in liquid culture. Similar populations of siderophore-producing bacteria were observed on roots of St. Augustine grass, which frequently exhibits Fe chlorosis, and bermuda grass, which does not. Roots of both grasses were colonized by bacteria that produced siderophore in vitro at concentrations ranging from 100 to 230 μM. The CAS assay solution was also used to compare siderophore production by Pseudomonas fluorescens Q6, an isolate from bermuda grass, and by P. putida B 10, a plant growth-promoting pseudomonad. P. fluorescens Q6 produced 2.4 times more siderophore in vitro than P. putida B 10.
Preliminary results on pregnancy outcomes in women using lamotrigine.

Summary: Purpose: In 1992, the International Lamotrigine Pregnancy Registry was initiated to enroll prospectively and to monitor pregnancies exposed to lamotrigine (LTG) for the occurrence of major birth defects. This study presents results as of September 2001 on 168 outcomes exposed to LTG monotherapy and 166 outcomes after pregnancies exposed to LTG polytherapy during the first trimester. Methods: LTG pregnancy exposures are voluntarily reported to the registry by health care providers before they are aware of each pregnancy outcome. Pregnancy-outcome ascertainment is obtained through subsequent follow-up with the reporting health care provider, and each reported birth defect is reviewed by an expert pediatrician. The percentage with major birth defects in pregnancies with known birth defect status was calculated for LTG monotherapy and for polytherapy stratified by trimester of exposure. Results: The registry identified 334 first-trimester LTG pregnancy outcomes exposed to LTG monotherapy or polytherapy during the first trimester and involving either a live birth with or without a major birth defect or an abortion with a major birth defect. After exposure to LTG monotherapy, the percentage with major birth defects exposed to LTG monotherapy was three (1.8%) of 168 [95% confidence interval (CI), 0.5–5.5%]. There were five (10%) major birth defects observed in 50 outcomes after LTG polytherapy involving valproic acid (VPA; 95% CI, 3.7–22.6%) during the first trimester. The observed proportion of major defects after LTG polytherapy without VPA during the first trimester was five (4.3%) of 116 (95% CI, 1.6–10.3%). No specific patterns of major birth defects in any subgroup or within the registry as a whole were observed. Conclusions: The sample sizes for individual regimens are too small to rule out small increases in frequency of all major birth defects or even large increases in frequency of rare major birth defects. However, the percentage of outcomes with major birth defects after LTG monotherapy in this study and in another similar pregnancy registry in the United Kingdom did not differ from that reported in the recent literature for women with epilepsy receiving antiepileptic drug monotherapy (4%). The frequency of major malformations after exposures of LTG–VPA is higher than that after the LTG monotherapy or LTG polytherapy regimens without VPA. Although there are published data on frequency of major malformations after VPA exposures in pregnancy, between-study differences in methods and source populations and the wide confidence intervals around the estimate for LTG and VPA limit the utility of comparison with such data, and no conclusions are made at this time about this combination. The continued registration of exposed pregnancies to an exposure registry as early as possible in the pregnancy before any knowledge of the outcome, and before any prenatal testing, will enhance the power of such data.
Direct manipulation through surrogate objects

Direct manipulation has had major influence on interface design since it was proposed by Shneiderman in 1982. Although directness generally benefits users, direct manipulation also has weaknesses. In some cases, such as when a user needs to manipulate small, attribute-rich objects or multiple objects simultaneously, indirect manipulation may be more efficient at the cost of directness or intuitiveness of the interaction. Several techniques have been developed over the years to address these issues, but these are all isolated and limited efforts with no coherent underlying principle. We propose the notion of Surrogate Interaction that ties together a large subset of these techniques through the use of a surrogate object that allow users to interact with the surrogate instead of the domain object. We believe that formalizing this family of interaction techniques will provide an additional and powerful interface design alternative for interaction designers, as well as uncover opportunities for future research.