cssi/SciSciGPT-SciSciNet huggingface dataset:
Actin-Dependent Activation of Presynaptic Silent Synapses Contributes to Long-Term Synaptic Plasticity in Developing Hippocampal Neurons

Developing neurons have greater capacity in experience-dependent plasticity than adult neurons but the molecular mechanism is not well understood. Here we report a developmentally regulated long-term synaptic plasticity through actin-dependent activation of presynaptic silent synapses in cultured hippocampal neurons. Live FM 1-43 imaging and retrospective immunocytochemistry revealed that many presynaptic boutons in immature neurons are functionally silent at resting conditions, but can be converted into active ones after repetitive neuronal stimulation. The activation of presynaptic silent synapses is dependent on L-type calcium channels and protein kinase A (PKA)/PKC signaling pathways. Moreover, blocking actin polymerization with latrunculin A and cytochalasin B abolishes long-term increase of presynaptic functional boutons induced by repetitive stimulation, whereas actin polymerizer jasplakinolide increases the number of active boutons in immature neurons. In mature neurons, however, presynaptic boutons are mostly functional and repetitive stimulation did not induce additional enhancement. Quantitative immunostaining with phalloidin revealed a significant increase in axonal F-actin level after repetitive stimulation in immature but not mature neurons. These results suggest that actin-dependent activation of presynaptic silent synapses contributes significantly to the long-term synaptic plasticity during neuronal development.
Lactation curves in dairy goats: a review

Abstract Only a few dairy goat studies have modeled lactation curves using a mathematical function. Among them, the multiphasic function provides the most useful information on characteristics of the lactation curve including scale (initial and maximum yields) and shape (time of maximum yield and persistence). Factors that affect such characteristics include breed, parity, season of kidding and level of production. Breed affects scale of the curve; parity affects scale and shape; season of kidding mainly affects shape (persistency); and level of production affects scale and shape (persistency). The multiphasic function warrants further consideration as the model for lactation curves in dairy goats. Further genetic and physiological research is needed to understand fully the biological properties of phases of the lactation curve in dairy goats and to ascertain their usefulness in management and in selection.
Massive upregulation of the Fas ligand in lpr and gld mice : implications for Fas regulation and the graft-versus-host disease-like wasting syndrome

Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of T cells with an unusual double negative (DN) (CD4-CD8-) phenotype. Previous studies have shown that these abnormal cells are capable of inducing redirected lysis of certain Fc receptor-positive target cells. Since the Fas ligand (FasL) has recently been shown to be partly responsible for T cell-mediated cytotoxicity, lymph node cells from lpr and gld mice were examined for the expression of FasL mRNA. Northern blot analysis revealed that lymph node cells obtained from lpr and gld mice had a striking increase in the level of expression of FasL mRNA predominantly due to expression in the DN T cells. Furthermore, lpr, but not gld lymph node cells killed the B cell line, A20, in a Fas-dependent manner. These findings indicate that Fas mutations result in a massive up-regulation of FasL which, most likely, results from repetitive exposure to (self) antigen. This phenomenon could explain the lpr-induced wasting syndrome observed when lpr bone marrow-derived cells are adoptively transferred to wild-type recipients.
K -shell photoabsorption spectra of N 2 and N 2 O using synchrotron radiation

The total photoionization cross section of the $1s$ level of nitrogen in ${\mathrm{N}}_{2}$ and ${\mathrm{N}}_{2}$O molecules has been measured using monochromatized synchrotron radiation. High-resolution spectra in the range $390l\ensuremath{\hbar}\ensuremath{\omega}l450$ eV were recorded. A broadband in the continuum at 9.4 eV above the ionization threshold, due to the $f$-type shape resonance, has been measured with high resolution. The data are compared with theoretical calculations of photoionization cross section. Recent Hartree-Fock calculations in the static-exchange approximation agree better than earlier results, which employed the multiple-scattering method.
Cardiovascular and muscular effects of venom from coral snake, Micrurus fulvius

Abstract The effect of lyophilized Micrurus fulvius venom on cardiovascular and neuro-muscular function was studied in anesthetized cats and in rat muscle preparations in vitro. Respiratory paralysis occurred prior to cardiac failure in cats. Paralysis of the twitch response to nerve stimulation paralleled respiratory depression. Death occurred later through cardiac depression despite artificial ventilation. The twitch response of rat phrenic nerve-diaphragm to direct and indirect stimulation was depressed by venom over a time course of 4 hr. Depression of twitch response to direct stimulation of the muscle was also observed in soleus and toe muscle, and was not affected by curarization. The resting membrane potential of the rat soleus muscle fell to 13 mV 2 hr after envenomation. Microscopic examination of muscle fibers revealed swelling and hyaline degeneration. No myoglobin release was demonstrated in envenomated rats.
Aerosols from Sahara weaken cyclogenesis

Hot, dry air and dust in the atmosphere over the Sahara Desert—known as the Saharan Air Layer (SAL)—are thought to influence cyclone formation when they interact with the cooler, more humid air over the Atlantic Ocean. Whether the SAL inhibits the formation of cyclones or not has been hotly debated for decades.
Scattering of a Rayleigh Wave by an Elastic Wedge Whose Angle is Greater Than 180 Degrees

The steady-state problem of scattering of an incident Rayleigh wave by an elastic wedge whose angle is greater than 180 degrees is considered. The problem is reduced to the numerical solution of a pair of Fredholm integral equations of the second kind whose kernels consist of elementary functions. Numerical results are given for the amplitude and phase of the Rayleigh waves transmitted and reflected by the corner.
A molecular mechanics and dynamics study of the minor adduct between DNA and the carcinogen 2-(acetylamino)fluorene (dG-N2-AAF).

Experimental studies involving the carcinogenic aromatic amine 2-(acetylamino)fluorene (AAF) have afforded two acetylated DNA adducts, the major one bound to C8 of guanine and a minor adduct bound to N2 of guanine. The minor adduct may be important in carcinogenesis because it persists, while the major adduct is rapidly repaired. Primer extension studies of the minor adduct have indicated that it blocks DNA synthesis, with some bypass and misincorporation of adenine opposite the lesion [Shibutani, S., and Grollman, A.P. (1993) Chem. Res. Toxicol. 6, 819-824]. No experimental structural information is available for this adduct. Extensive minimized potential energy searches involving thousands of trials and molecular dynamics simulations were used to study the conformation of this adduct in three sequences: I, d(C1-G2-C3-[AAF]G4-C5-G6-C7).d(G8-C9-G10-C11-G12-C13-G14+ ++); II, the sequence of Shibutani and Grollman, d(C1-T2-A3-[AAF]G4-T5-C6-A7).d(T8-G9-A10-C11-T12-A13-G14); and III, which is the same as II but with a mismatched adenine in position 11, opposite the lesion. AAF was located in the minor groove in the low-energy structures of all sequences. In the lowest energy form of the C3-[AAF]G4-C5 sequence I, the fluorenyl rings point in the 3' direction along the modified strand and the acetyl in the 5' direction. These orientations are reversed in the second lowest energy structure of this sequence, and the energy of this structure is 1.4 kcal/mol higher. Watson Crick hydrogen bonding is intact in both structures. In the two lowest energy structures of the A3-[AAF]G4-T5 sequence II, the AAF is also located in the minor groove with Watson-Crick hydrogen bonding intact. However, in the lowest energy form, the fluorenyl rings point in the 5' direction and the acetyl in the 3' direction. The energy of the structure with opposite orientation is 5.1 kcal/mol higher. In sequence III with adenine mismatched to the modified guanine, the lowest energy form also had the fluorenyl rings oriented 5' in the minor groove with intact Watson-Crick base pairing. However, the mispaired adenine adopts a syn orientation with Hoogsteen pairing to the modified guanine. These results suggest that the orientation of the AAF in the minor groove may be DNA sequence dependent. Mobile aspects of favored structures derived from molecular dynamics simulations with explicit solvent and salt support the essentially undistorting nature of this lesion, which is in harmony with its persistence in mammalian systems.
Detection of Group B Streptococcus by immunoassay following enrichment in LIM-selective broth medium

Abstract Rapid immunoassays have been developed to decrease the time to detection of Group B Streptococcus (GBS) carriage in pregnant women. In this study, a total of 162 pregnant women, considered to be high-risk obstetric patients, were seen in the Family Care Center at Memorial Hospital of Rhode Island, a 300-bed teaching hospital associated with Brown University Medical School. Vaginal and rectal specimens were taken and tested for GBS by using two rapid enzyme immunoassays (EIAs) that were compared with culture. Quidel and Hybritech ICON Group B strep tests were run following 4 h incubation in the selective enrichment LIM Group B strep broth; cultures were done both directly and after enrichment. Results with both EIAs were identical, with overall sensitivity, specificity, and positive and negative predictive values of 38%, 98%, 88%, and 84% respectively. However, when women having positive cultures were separated into moderately to heavily colonized (≥3 + ) and lightly colonized (≤2 + ) populations, the sensitivities were 82% and 19%, respectively. Although GBS assays are useful in the rapid diagnosis of heavily colonized women, culture following enrichment remains the most sensitive method for a lightly colonized population.
Samples and systems: finding the fit to improve care for adolescent depression.

The papers in this special issue wrestle with two similar but separable questions—how can we best improve youth mental health, and how can we better the youth mental health system? Both questions are of high consequence. The mental health needs of the nation’s (and the world’s) youth are well-documented and dire. In the United States, we have developed an elaborate and expensive set of institutions devoted to providing mental health services to address these needs, although serious questions have been raised about the effectiveness of these services in reducing psychiatric disorder and improving youth functioning. Thus, it would be eminently rational to link these queries— improving youth mental health rightly ought to involve improving the youth mental health system. However, despite the logic of this prescription, we find ourselves sympathetic to the ‘‘separatist’’ view of these questions, as expressed across this special issue. This is due, in part, to the impact systems have on defining samples. Characteristics of systems influence who seeks and receives care in particular settings, and the characteristics of youth and families further shape the needs and missions of these
Serum Protein Binding of Exogenous Insulin in Menstruating and Pregnant Diabetic Patients

Insulin binding by insulin antibodies was determined serially in eight menstruating and in twelve pregnant diabetic subjects. No significant variation was noted in the insulin binding values before, during or after menstruation or during or after pregnancy. This constancy of insulin binding was observed despite major and minor changes in insulin needs. No causal relationship could be demonstrated between insulin binding by insulin antibodies and changing insulin requirements. If there is a relationship between the hormonal changes and the alterations in insulin needs during menstruation and pregnancy, the mechanism of this relationship is not mediated through the insulin binding capacity of circulating insulin antibodies.
The Use of Anti-inflammatory Medications in Cystic Fibrosis: Trends and Physician Attitudes

Study objectives: In recent years, there has been considerable interest in the use of antiinflammatory medications to decrease airway inflammation and preserve pulmonary function in patients with cystic fibrosis (CF) lung disease. Long-term use of oral corticosteroids (OCS) and ibuprofen (IBU) has been proven efficacious in slowing the progression of CF. Inhaled corticosteroids (ICS) have not been adequately studied. Little is known regarding use trends and physician attitudes toward these drugs. Design: Cross-sectional survey mailed to 111 directors of Cystic Fibrosis Centers in the United States accredited by the Cystic Fibrosis Foundation. The two-page written questionnaire included items regarding physicians’ attitudes toward anti-inflammatories, center demographics, patients receiving therapy, and number of physicians prescribing therapy. Results: Sixty-seven surveys were returned (60%). The responding centers represented 239 physicians and served 9,363 patients, 2,234 (24%) of whom were receiving routine antiinflammatory drugs. Complete data sets were available for 8,803 patients with 2,169 (25%) receiving anti-inflammatory therapy. Ninety-eight (41%) physicians prescribed long-term use of oral steroids for 413 (5%) patients, 103 (42%) prescribed inhaled steroids for 1,032 (12%) patients, and 108 (45%) prescribed high-dose IBU for 723 (8%) patients to control CF. The practitioners reported familiarity and efficacy as the primary reasons for prescribing OCS; concerns over side effects were the major reason for not prescribing. Regarding ICS, the primary reasons for prescribing were familiarity and safety, with lack of efficacy being cited as the major reason for not prescribing. For IBU, efficacy was ranked highest among reasons for prescribing, with concern over safety being the highest ranked reason for not prescribing. Conclusions: Anti-inflammatory medications appear to be an underutilized therapeutic modality in CF care. This is true for numbers of patients receiving these drugs as well as numbers of care providers prescribing them. Additional studies will be required to address physicians’ concerns regarding the long-term efficacy and safety of anti-inflammatory drugs in treating CF. (CHEST 1999; 115:1053‐1058)
The Many Faces of Manhood: Examining Masculine Norms and Health Behaviors of Young Fathers Across Race

This study examined the relationship between the traditional masculine norms ("status," "toughness" and "antifemininity") of 296 ethnically and racially diverse, young men transitioning to fatherhood and substance use (smoking, alcohol, marijuana, hard drugs) and health behaviors (diet, exercise). Participants were recruited from urban obstetric clinics in the Northeast United States. Logistic and multiple regression equations were constructed to examine the relationship between masculine norms and health behaviors. Moderator effects were also examined. Masculine norm "status" was most endorsed and "antifemininity" was least endorsed. African American young men had higher masculine norm scores than Latino and Whites. Different masculine norms were associated with health-promoting and health-undermining behaviors. Different racial groups who had higher scores on some masculine norms were more likely to engage in either health-promoting or health-undermining behaviors when compared with other ethnic groups in this study. These results observed different relationships between the traditional masculine norms measured and the substance use and health behaviors of diverse, young men transitioning to fatherhood. This may have implications for intervention strategies and future research.
Telemedicine: a solution to the followup of rural trauma patients?

Abstract Background: Outpatient followup of rural trauma patients is problematic for physicians and patients. Our hypothesis was that telemedicine-based followup of trauma patients discharged to remote areas is feasible and is associated with high patient and physician satisfaction. Study Design: We chose 11 counties in Kentucky surrounding a remote telemedicine site as our region of interest. Any adult trauma patient who was discharged from our Level I trauma center to this geographic region was eligible to have routine followup appointment(s) at the TeleTrauma Clinic. Patients were examined and interviewed with the assistance of a nurse, an electronic stethoscope, and a close-up imaging instrument. Radiographs performed at the telemedicine site were viewed. Patients and physicians completed a survey after the appointment. Results: To date, we have conducted 22 telemedicine-based followup assessments of trauma patients. The average age and Injury Severity Score were 42 years and 18, respectively. Plain radiographs were reviewed in 13 cases. Our patient surveys indicated a high degree of satisfaction with the teleappointment. In 15 of 22 patients, no further clinical followup was arranged. The differences in travel distances and times for an appointment at the TeleTrauma Clinic versus an appointment at our Level I trauma center were significant. The average and median duration of the appointments was 14 minutes. All telemedicine encounters were done by two physicians, who recorded a high level of satisfaction. Conclusions: Our early experience with the outpatient followup of remote trauma victims by telemedicine is encouraging. Patient surveys indicate a high degree of satisfaction. As a result of our favorable experience, telemedicine-based followup may be expanded to other regions of Kentucky.
DREAM: dynamic resource allocation for software-defined measurement

Software-defined networks can enable a variety of concurrent, dynamically instantiated, measurement tasks, that provide fine-grain visibility into network traffic. Recently, there have been many proposals to configure TCAM counters in hardware switches to monitor traffic. However, the TCAM memory at switches is fundamentally limited and the accuracy of the measurement tasks is a function of the resources devoted to them on each switch. This paper describes an adaptive measurement framework, called DREAM, that dynamically adjusts the resources devoted to each measurement task, while ensuring a user-specified level of accuracy. Since the trade-off between resource usage and accuracy can depend upon the type of tasks, their parameters, and traffic characteristics, DREAM does not assume an a priori characterization of this trade-off, but instead dynamically searches for a resource allocation that is sufficient to achieve a desired level of accuracy. A prototype implementation and simulations with three network-wide measurement tasks (heavy hitter, hierarchical heavy hitter and change detection) and diverse traffic show that DREAM can support more concurrent tasks with higher accuracy than several other alternatives.
Reaction synthesis of Ti3SiC2 phase in plasma sprayed coating

This investigation focuses on the feasibility of reaction synthesis of Ti3SiC2 phase using plasma spraying of powder mixture of Ti, SiC and graphite. In-flight particle diagnostics suggested that dwell (reaction) time of these powder mixture is very short (∼10 −4 s) during plasma spraying. Phase identification and microstructural characterizations of the as-sprayed coatings were conducted using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Thermodynamic calculations on Ti–SiC–C system were also made. Reaction mechanism of Ti3SiC2 synthesis during plasma spray is proposed. Although relatively lower volume percentage of Ti3SiC2 (∼15–19%) phase was found in the plasma sprayed coating, reaction synthesis of Ti3SiC2 phase using plasma spray provides a potential processing technique to fabricate Ti3SiC2 as a protective coating on large engineering components.
The major transitions of life from a network perspective.

Many attempts have been made to understand the origin of life and biological complexity both at the experimental and theoretical levels but neither is fully explained. In an influential work, Maynard Smith and Szatmary(The major transitions in evolution. Oxford; New York: W.H. Freeman Spektrum, 1995) argued that the majority of the increase in complexity is not gradual, but it is associated with a few so called major transitions along the way of the evolution of life. For each major transition, they identified specific mechanisms that could account for the change in complexity related to information transmission across generations. In this work, I propose that the sudden and unexpected improvement in the functionality of an organism that followed a major transition was enabled by a phase transition in the network structure associated with that function. The increase in complexity following a major transition is therefore directly linked to the emergence of a novel structure-function relation which altered the course of evolution. As a consequence, emergent phenomena arising from these network phase transitions can serve as a common organizing principle for understanding the major transitions. As specific examples, I analyze the emergence of life, the emergence of the genetic apparatus, the rise of the eukaryotic cells, the evolution of movement and mechanosensitivity and the emergence of consciousness. Finally, I discuss the implications of network associated phase transitions to issues that bear relevance to the history, the immediate present and perhaps the future, of life.
RELIABILISM AND ANTIREALIST THEORIES OF TRUTH

In order to shed light on the question of whether reliabilism entails or excludes certain kinds of truth theories, I examine two arguments that purport to establish that reliabilism cannot be combined with antirealist and epistemic theories of truth. I take antirealism about truth to be the denial of the recognition-tran- scendence of truth, and epistemic theories to be those that identify truth with some kind of positive epistemic status. According to one argument, reliabilism and anti- realism are incompatible because the former takes epistemic justification to be rec- ognition-transcendent in a certain sense that conflicts with the latters denial of the recognition-transcendence of truth. I show that, because the recognition-transcen- dence of reliabilist justification is significantly weaker than the recognition-tran- scendence required by a realist conception of truth, antirealist theories of truth that deny the strong transcendence of truth do not threaten the externalist character of reliabilism. According to the second argument, reliabilism cannot be combined with an epistemic truth theory because reliabilists analyze positive epistemic status in terms of truth but epistemic theorists analyze truth in terms of positive epistemic status. However, I argue that reliabilists who wish to adopt an epistemic theory of truth can avoid circularity by appealing to a multiplicity of positive epistemic statuses.
Part "D" for "Defective" — The Medicare Drug-Benefit Chaos

A recent survey quantifies what many of us have seen firsthand: the new Medicare drug benefit is having a troubled infancy. Dr. Jerry Avorn discusses the continuing debate over whether its early spasticity was caused by inept management of its birth or a genetic disorder present at its creation.
Polymorphic versus Monomorphic Flow-Insensitive Points-to Analysis for C

We carry out an experimental analysis for two of the design dimensions of flow-insensitive points-to analysis for C: polymorphic versus monomorphic and equality-based versus inclusion-based. Holding other analysis parameters fixed, we measure the precision of the four design points on a suite of benchmarks of up to 90,000 abstract syntax tree nodes. Our experiments show that the benefit of polymorphism varies significantly with the underlying monomorphic analysis. For our equality-based analysis, adding polymorphism greatly increases precision, while for our inclusion-based analysis, adding polymorphism hardly makes any difference. We also gain some insight into the nature of polymorphism in points-to analysis of C. In particular, we find considerable polymorphism available in function parameters, but little or no polymorphism in function results, and we show how this observation explains our results.
The association between recipient alcohol dependency and long-term graft and recipient survival.

BACKGROUND: The causative role of alcohol consumption in renal disease is controversial, and its effect on renal graft and recipient survival has not been previously studied. METHODS: We analysed the association between pre-transplant [at the time of end-stage renal disease (ESRD) onset] alcohol dependency and renal graft and recipient survival. The United States Renal Data System (USRDS) records of kidney transplant recipients 18 years or older transplanted between 1 January 1995 and 31 December 2002 were examined. We used Kaplan-Meier analysis and Cox regression models adjusted for covariates to analyse the association between pre-transplant alcohol dependency and graft and recipient survival. RESULTS: In an entire study cohort of 60 523, we identified 425 patients with a history of alcohol dependency. Using Cox models, alcohol dependency was found to be associated with increased risk of death-censored graft failure [hazard ratio (HR) 1.38, P < 0.05] and increased risk of transplant recipient death (HR 1.56, P < 0.001). Subgroup analysis demonstrated an association of alcohol-dependency with recipient survival and death-censored graft survival in males (but not in females), and in both white and non-white racial subgroups. CONCLUSIONS: We concluded that alcohol dependency at the time of ESRD onset is a risk factor for renal graft failure and recipient death.
Edge wave visualization

Scattering mechanisms that involve edge waves are addressed. The behavior of edge waves and their interaction with flat perfectly conducting plates are depicted in the time domain through a visualization of surface currents that flow on the surface, as an incident Gaussian pulse of energy washes over the surface. Viewing these surface currents allows a very clear physical interpretation and appreciation of the scattering process. >
XPOSE: a simulator for network development

XPOSE is a network simulator developed at IBM that combines the strengths of architecture-oriented simulators and hardware/software co-simulators. It provides a platform to develop and debug operational and system test software prior to delivery of actual hardware. XPOSE can also be used to assist hardware designers in verifying VHDL functional models for architectural correctness. The XPOSE design is described and examples are given from operational experience related to plaNET/ORBIT gigabit network development efforts. These examples highlight the ease-of-use, modularity, dynamic configurability and selective granularity of simulation provided by XPOSE. >
The stabilized probability plot

SUMMARY The stabilized probability plot is introduced. An attractive feature of the plot that enhances its interpretability is that the variances of the plotted points are approximately equal. This prompts the definition of a new and powerful goodness-of-fit statistic Dsp which, analogous to the standard Kolmogorov-Smirnov statistic D, is defined to be the maximum deviation of the plotted points from their theoretical values. Using either D or Dsp it is shown how to construct acceptance regions for QQ,, Pp and the new plots. Acceptance regions can help remove much of the subjectivity from the interpretation of these probability plots.
Computer energy management systems problems and resolutions

Summary form only given, as follows. Factors that influence the degree in which the acquisition and continued operation of new and fairly complex technologies are successful have been investigated. The study examines 14 multi-building sites in which computer energy manager systems (CEMS) were installed. A CEMS includes hardware, sensors, software, programming, analysis, and dynamic systems controls. The average age of an installation is eight years. Three measures of success are compared relative to 25 factors identified as likely to influence success. The factors fall into eight categories: age, size, scope, installation, plant condition, vendor support, in-house staffing, and system components. The findings suggest that being a customer on the cutting edge of an evolving arrangement of new technologies is very risky. Very close supervision and the development and maintenance of in-house competence relative to the new technologies can offset the risk. Rapid development in computer hardware and software overcomes early problems, but poses challenges in transitioning from one generation to the next. >
Crystal Structure of the Pseudomonas aeruginosa Virulence Factor Regulator

ABSTRACT Virulence factor regulator (Vfr) enhances Pseudomonas aeruginosa pathogenicity through its role as a global transcriptional regulator. The crystal structure of Vfr shows that it is a winged-helix DNA-binding protein like its homologue cyclic AMP receptor protein (CRP). In addition to an expected primary cyclic AMP-binding site, a second ligand-binding site is nestled between the N-terminal domain and the C-terminal helix-turn-helix domain. Unlike CRP, Vfr is a symmetric dimer in the absence of DNA. Removal of seven disordered N-terminal residues of Vfr prevents the growth of P. aeruginosa.
Chimeric Exchange of Coronavirus nsp5 Proteases (3CLpro) Identifies Common and Divergent Regulatory Determinants of Protease Activity

Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of severe human respiratory disease. A conserved step of CoV replication is the translation and processing of replicase polyproteins containing 16 nonstructural protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a conserved 3-domain structure and catalytic residues. However, the intra- and intermolecular determinants of nsp5 activity and their conservation across divergent CoVs are unknown, in part due to challenges in cultivating many human and zoonotic CoVs. To test for conservation of nsp5 structure-function determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV) genomes encoding nsp5 proteases of human and bat alphacoronaviruses and betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral recovery with efficient replication albeit with impaired fitness in direct competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear differences in viability and temperature-sensitive phenotypes compared with MHV nsp5. These data indicate tight genetic linkage and coevolution between nsp5 protease and the genomic background and identify differences in intramolecular networks regulating nsp5 function. Our results also provide evidence that chimeric viruses within coronavirus genogroups can be used to test nsp5 determinants of function and inhibition in common isogenic backgrounds and cell types.
Memorandum Quod: John Fastolf and the Founding of Magdalen College

Magdalen College in Oxford was founded in 1458 by William Waynflete, Bishop of Winchester. This article discusses the role of Sir John Fastolf, a special benefactor of the college, in the founding. As this article explains, Fastolf’s property played a significant role in enabling Bishop Waynflete to establish Magdalen College.
Anesthesia Machines: Demystifying Their Function

The goal of all anesthesia care is to ensure the safest possible experience for the patient. Tremendous advances have been made in design, safety aspects, and monitoring. Advances also have been made in acquiring and quantifying physiologic data during surgery; however, this abundance of information can confuse as well as inform. Recent efforts have been directed toward integrating alarms and monitoring devices to detect high-risk situations (eg, airway disconnect leading to hypoxemia, bradycardia, and eventually cardiac arrest). Commensurate with advances in biomedical instrumentation and ergonomics is preservation of the fundamental concept of monitoring--that the anesthetist/anesthesiologist is the most essential monitor to integrate information and develop a rational plan of intervention.
Alcohol and suicidal behavior: What is known and what can be done

Research on associations between substances of abuse and suicidal behaviors is a large, complex area. Herein, alcohol, the most commonly abused intoxicant worldwide, is examined with a focus on two topics: (1) acute use of alcohol (AUA) shortly prior to suicidal behavior; and (2) more chronic alcohol use disorder (AUD) and suicidal behavior. First, a brief summary of what is known about AUA, AUD, and suicidal behavior is provided. Next, we draw on preliminary evidence, practical considerations, and our own experience to offer recommendations for intervention research that may lower risk associated with AUA and AUD. The literature on AUD and suicidal behavior is more developed, thus we discuss separately research designed to: (1) prevent individuals with AUD with suicidal ideation from engaging in suicidal behavior; and (2) prevent individuals with AUD who have made a suicide attempt from reattempting. Our focus is on clinical intervention strategies for individuals at risk for suicidal behavior that use alcohol or have developed AUD. We also focus on applied research that may directly lead to practical prevention efforts. Although clinical interventions are important components of a comprehensive suicide prevention strategy, they should be complemented with primary prevention efforts.
Pharmacologic Therapy of Diabetes and Overall Cancer Risk and Mortality: A Meta-Analysis of 265 Studies

Pharmacologic Therapy of Diabetes and Overall Cancer Risk and Mortality: A Meta-Analysis of 265 Studies
CHANGES IN TRANSCRIPTS ENCODING CALCIUM CHANNEL SUBUNITS OF RAT MYOMETRIUM DURING PREGNANCY

Extracellular Ca2+ is normally required for myometrial cells to contract. Ca2+ enters muscle cells mainly through voltage-dependent Ca2+ channels (VDCCs) that open in response to action potentials. The synthesis of myometrial VDCCs may change during pregnancy to alter excitation-contraction coupling. We investigated the mRNA levels for the alpha 1- and beta-subunits of the L-type VDCC in rat myometrium to determine whether alterations are associated with term or preterm labor. RNA isolated from myometrial tissues was analyzed by reverse transcription-polymerase chain reaction (PCR) using specific primers designed according to the published sequences of the VDCC subunits. From pregnant rat myometrium, two distinct PCR products were obtained for the alpha 1-subunit: one of the expected size at 372 bp and a smaller at 339 bp. Sequence analysis of the larger product revealed a 99.5 or 88% sequence homology between rat myometrium and rat aorta or rabbit heart, respectively, and the smaller product had an identical sequence to a 33-bp deletion. The two alpha 1-products followed the same trend throughout pregnancy. VDCC alpha 1-mRNA levels increased gradually to 6.9-fold just before labor on day 22 but decreased during labor. However, the beta-subunit mRNA level increased sharply on day 22 and then also declined during labor. Progesterone treatment from day 19 to day 22 inhibited term delivery and prevented the significant increase in alpha 1-mRNA levels. In contrast, antiprogesterone (onapristone, ZK-98.299) treatment on day 17 caused a statistically significant increase in the alpha 1- and beta-VDCC subunit mRNA after 8 and 15 h, respectively, then a decrease during preterm labor at 24 h. We conclude that mRNA levels for the VDCC subunits increase before term and preterm labor but decline during periods when VDCCs are likely at their peaks. The increase in levels of mRNA for VDCC likely reflects changes in expression of VDCCs during periods of term and preterm labor that may facilitate uterine contractility required for this process. Progesterone withdrawal or blockade appears to be responsible for regulating levels of mRNA for VDCC in the myometrium in preparation for labor.
Preliminary Experience with the Treatment of Intracranial Vasospasm by Transvascular Balloon Angioplasty

Microneurosurgical advances have greatly decreased the morbidity and mortality associated with ruptured intracranial aneurysms, particularly in patients with good clinical status. In patients with poor clinical status, the devastating effects of hemorrhage on the cerebral circulation can result in ischemia and infarction. Early neurosurgical clipping allows more aggressive postoperative management of delayed cerebral vasospasm with volume expansion and hypertension. Early surgery has shown a decreased incidence of delayed vasospasm if the clot surrounding the cerebral vasculature can be removed [8]. In patients with delayed cerebral vasospasm with an untreated aneurysm, treatment with hypertension and volume expansion can increase the risk of rehemorrhage. In the United States, as many as 11% of patients with ruptured aneurysms will die secondary to the ischemic consequences of vasospasm, and considerably more will be permanently disabled [7].
Commentary: discovering a different model of medical student education.

Traditional medical schools in modern academic health centers make discoveries, create new knowledge and technology, provide innovative care to the sickest patients, and educate future academic and practicing physicians. Unfortunately, the growth of the research and clinical care missions has sometimes resulted in a loss of emphasis on the general professional education of medical students. The author concludes that it may not be practical for many established medical schools to functionally return to the reason they were created: for the education of medical students.He had the opportunity to discover a different model of medical student education at the first new MD-granting medical school created in the United States in 25 years (in 2000), the Florida State University College of Medicine. He was initially skeptical about how its distributed regional campuses model, using practicing primary care physicians to help medical students learn in mainly ambulatory settings, could be effective. But his experience as a faculty member at the school convinced him that the model works very well.He proposes a better alignment of form and function for many established medical schools and an extension of the regional community-based model to the formation of community-based primary care graduate medical education programs determined by physician workforce needs and available resources.
Failure of Sodium Iodide Loading To Inhibit Renin in the Rat

SummaryNaCl-deprived rats given Nal to drink failed to suppress PRA compared to rats drinking equimolar amounts of NaCl, despite a more positive Na balance in the former group. Volume contraction and potassium deficiency do not appear to explain this observation. If chloride is a principal ion to signal the macula densa to release renin, our data suggest that iodide cannot substitute in such a role.
Respiratory Response against Exercise under the Condition of Experimentally Restricted Lung Function

In order to examine respiratory reaction agaist exercise of patients with respiratory dysfunction, three exercise load tests were performed on healthy adults; without restriction (test 1), with restricted movementof thorax and abdominal part (test 2), and with restricted exchange of gas by experimentally blockading the upper part of the respiratory tract (test 3). Results obtained were; with increasing the exercise load. 1)three groups showed almost the same increase in heart rate, 2)ventilation volume of one breathing increased in all the three groups, test 2 groups indicatig lower, and test 3 group higher ventilation volume compared with test 1 group, 3)respiration rate increased in all the three groups, test 2 group showing higher, and test 3 group lower respiration rate than test 1 group, 4)compared with test 1 group, test2 group showed a slight increaseand test 3 group decrease in ventilation effect, and 5)in contradiction to our hypotheses, tests 2 and 3 groups showed relativelly lower value of MMT than test 1 group.
The International Cognitive Ability Resource: The case for its broader use and collaborative development

A prominent goal of individual differences research is the development and testing of models which predict important life outcomes. Prior work suggests that the most predictive models for many outcomes integrate multiple dimensions of individual differences and that three of the most informative dimensions are temperament, cognitive abilities and interests. Of these three, large-scale assessment of cognitive abilities has been the most problematic due to methodological constraints. Recent and ongoing development of the public-domain International Cognitive Ability Resource is intended to address these constraints. In this talk, we will describe the procedures being used to develop this resource and summarize progress to date. Then, using online data collected with synthetic aperture personality assessment (”SAPA”) methods (sapa-project.org), we compare the predictive utility of integrated individual difference models against those which use only the independent dimensions (of temperament or interests or ability) in the context of academic, occupational and health outcomes.
Coronary thromboendarterectomy for angina pectoris.

Total occlusion of one or more major coronary arteries by atherosclerosis is characteristically found in the majority of patients with the clinical manifestations of severe angina pectoris.Sites of arterial obstruction in patients with severe angina pectoris may be localized precisely by coronary arteriography, and in selected cases it is possible to perform thromboendarterectomy under direct vision. The findings in a group of patients treated in this manner are presented and discussed. Results after a limited period of observation appear sufficiently encouraging to recommend this approach in the management of selected patients with intractable angina pectoris.
Emerging role of PET/MRI in Neurology: An update on the current applications and pitfalls.

1919 Learning Objectives 1. To provide an update over the diagnostic, prognostic and response assessment aspects of PET/MRI in neurologic disorders. 2. To review the clinical applications of PET/MRI in neurological disorders. PET/MRI appears to show superior diagnostic capabilities compared to PET/CT in the field of neurology and brain imaging. Combination of PET/MRI helps us to take advantage of MR specific characteristics such as enhanced soft tissue resolution and morphologic information, elimination of radiation dose compared to CT and quantitative MRI techniques such as diffusion MRI, dynamic contrast enhanced MRI and MR spectroscopy. Additionally, PET and its wide variety of radiotracers gives us the opportunity to gather information about metabolism, tumor biology, neurodegeneration, and many more features of the central and peripheral nervous system. In this presentation we will discuss: 1. Comparing performance of PET/MRI versus PET/CT for evaluation of central nervous system and peripheral nervous system disorders a. Soft tissue contrast resolution b. Radiation dose c. PET motion correction d. Partial volume effect correction 2. Clinical Applications of PET/MRI in patients with neurologic disorders a. Visualization of normal structures b. Brain Tumors and neoplasm of the nervous system c. Epilepsy and cortical dysplasia d. Dementia and neurodegenerative diseases e. Stroke
The evolution of grass genome organisation and function

New cloning technologies and more efficient DNA sequencing now permit comprehensive structural studies of complex eukaryotic genomes. Previous global investigations of genome organisation in plants had shown that abundant repetitive DNAs were intermixed with genes. However, the nature of the major repeats, their possible biological roles, their origins, and their precise patterns of organisation were not clearly defined. My laboratory has used large clones derived from homologous regions of the maize, sorghum and rice genomes to investigate the nature, functional properties and evolution of grass genome organisation. Unexpectedly simple patterns of genome composition and arrangement have been seen, and these appear to be similar in different grasses. Our detailed studies of the maize genome indicate that short (2-20 kb) blocks of gene-containing DNA alternate with large (2-200 kb) blocks of intermixed middle and highly repetitive DNAs. Most of the highly repetitive sequences, and many of the middle repetitive DNAs, are retrotransposons that have inserted within each other. These repetitive DNAs are usually methylated and mostly inactive, but they are homologous to transcripts found in many different tissues. The unmethylated DNA is composed primarily of genes interspersed with lower-copy-number retroelements and inverted-repeat transposable elements. Gene order and sequence are highly conserved, but the mobile DNAs between genes appear to be different due to their rapid evolution and their variable presence or locations in different grasses.
Hypertensive vascular disease and cerebral microcirculation

Cerebral microcirculation has a series of complex relationships with arterial hypertension determined, on one hand, by the size and the location of the vessels involved, and on the other hand, by the chronic or acute nature of the hypertension. The small arterial vessels of the cerebral parenchyma react to the effects of chronic hypertension with irreversible structural changes, whose pathologic and radiological correlation is chronic ischemia of the white substance, shown by paleness of the white substance, together with small lacunar infarctions, with a clinical association of dementia, motor disorders and pseudo-bulbar syndrome. With the appearance of an acute rise in arterial pressure, these vessels react with generally reversible changes which lead to an increase in the permeability of the hematoencephalic barrier with formation of cerebral edema and a clinical association generally demonstrating the focal nature of the vascular abnormality (such as in hypertensive encephalopathy with changes in posterior hemispheric predominance) or its unilateral location in cases in which the process occurs in one of the carotid territories (post-endarterectomy).