cssi/SciSciGPT-SciSciNet huggingface dataset:
Restoration of retinal development in Vsx2 deficient mice by reduction of Gdf11 levels.

The visual system homeobox 2 (Vsx2/Chx10) gene is required for proper eye development in vertebrates. In mouse, mutations in Vsx2 cause micro-ophthalmia, optic nerve aplasia, and failed retinal development, as well as aberrant retinal lamination. GDF11, a member of the TGF-β superfamily of signaling molecules known to function as an autocrine negative regulator of sensory neuron neurogenesis, has also been shown to have dramatic effects on retinal development: Absence of Gdf11 results in an increase in numbers of retinal ganglion cells, resulting from changes in the fates of retinal stem/progenitor cells in Gdf11 null retinas. In the present study, we performed genetic manipulations of the GDF11 signaling system to determine whether alterations in Gdf11 activity levels can improve retinal development in Vsx2-null mice. We found that removal of Gdf11 alleles in Vsx2 orJ/orJ mice can rescue retinal development and thickness to a substantial extent, and partially restores the expression of genes important for the development of specific types of retinal neurons. The molecular mechanism(s) by which reduction of Gdf11 activity enables rescue of retinal development in Vsx2 mutant animals is currently being investigated, and should provide important insights for potential treatment of retinal dystrophies.
PBC for direct voltage regulation for the boost DC–DC converter

Passivity-based control (PBC) for a power converter is an interesting alternative to the conventional linear control technique. In general, the objective of PBC is to reshape the energy of a system, additionally damping the system to modify the dissipation structure. PBC forces the closed-loop dynamics to behave in a manner such that the virtual damping resistances injected in the system are in series or parallel of the actual physical circuit elements. The boost converter is intrinsically non-linear, non-minimum phase system at the output with respect to the control input. Control techniques such as the PBC that requires some form of system inversion cannot be implemented. By using the one-to-one correspondence between the inductor current and the output voltage at the equilibrium point, conventional non-linear control techniques exploit regulation of the inductor current to regulate the output voltage (indirect regulation). This study proposes passivity-based direct output voltage regulation for a boost converter, which has multiple advantages over other non-linear control techniques and the conventional linear controller.
JCL roundtable: Lipid treatment targets.

Abstract This Roundtable discussion concerns atherogenic risk markers and treatment targets used by clinical lipidologists in daily practice. Our purpose is to understand the risk marker framework that supports and enables the new ACC/AHA/Multisociety Cholesterol Guidelines. Some biomarkers are highly associated with atherogenic risk but fail to qualify as treatment targets. Prominent examples are high-density lipoprotein cholesterol, for which targeted treatment has failed to reduce cardiovascular risk, and lipoprotein(a), which currently lacks a highly effective mode of treatment. As a consequence, guidelines have focused consistently on low-density lipoprotein cholesterol (LDL-C) and more recently on non–high-density lipoprotein cholesterol. We discuss a new calculation for LDL-C that shows greater accuracy than the commonly performed Friedewald calculation. LDL-C treatment goals have renewed prominence in the 2018 Guidelines. Thresholds for treatment initiation or intensification inherently establish goals of reducing atherogenic cholesterol levels below the thresholds. Treatment goals may be absolute, such as less than 70 mg/dL for LDL-C in very high-risk secondary prevention or relative, such as 50% or greater reduction of LDL-C. The timeframe of treatment is another consideration because milder treatment started earlier may sometimes be preferred over stronger treatment given late in the course of atherosclerotic progression. Advanced lipid testing and vascular imaging, particularly coronary artery calcium, also have their place in risk assessment to guide clinical lipid practice.
A Physical Model Approach to Gecko Adhesion Opportunity and Constraint: How Rough Could It Be?

It has been nearly 20 years since Autumn and colleagues established the central role of van der Waals intermolecular forces in how geckos stick. Much has been discovered about the structure and function of fibrillar adhesives in geckos and other taxa, and substantial success has been achieved in translating natural models into bioinspired synthetic adhesives. Nevertheless, synthetics still cannot match the multidimensional performance observed in the natural gecko system that is simultaneously robust to dirt and water, resilient over thousands of cycles, and purportedly competent on surfaces that are rough at drastically different length scales. Apparent insensitivity of adhesion to variability in roughness is particularly interesting from both a theoretical and applied perspective. Progress on understanding the extent to which and the basis of how the gecko adhesive system is robust to variation in roughness is impeded by the complexity of quantifying roughness of natural surfaces and a dearth of data on free-ranging gecko substrate use. Here we review the main challenges in characterizing rough surfaces as they relate to collecting relevant estimates of variation in gecko adhesive performance across different substrates in their natural habitats. In response to these challenges, we propose a practical protocol (borrowing from thermal biophysical ecological methods) that will enable researchers to design detailed studies of structure-function relationships of the gecko fibrillar system. Employing such an approach will help provide specific hypotheses about how adhesive pad structure translates into a capacity for robust gecko adhesion across large variation in substrate roughness. Preliminary data we present on this approach suggest its promise in advancing the study of how geckos deal with roughness variation. We argue and outline how such data can help advance development of design parameters to improve bioinspired adhesives based on the gecko fibrillar system.
Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation

Blood vessels in the central nervous system (CNS) develop unique features, but the contribution of CNS neurons to regulating those features is not fully understood. We report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevents invasion of endothelial cells into the deep layers of the retina and causes blood-retinal-barrier (BRB) dysfunction in mice. Vascular endothelial growth factor (VEGF), which drives angiogenesis, and Norrin, a Wnt ligand that induces BRB properties, are decreased after activity blockade. Exogenous VEGF restores vessel growth but not BRB function, whereas stabilizing beta-catenin in endothelial cells rescues BRB dysfunction but not vessel formation. We further identify that inhibiting cholinergic activity reduces angiogenesis during oxygen-induced retinopathy. Our findings demonstrate that neural activity lies upstream of VEGF and Norrin, coordinating angiogenesis and BRB formation. Neural activity originating from specific neural circuits may be a general mechanism for driving regional angiogenesis and barrier formation across CNS development.
Rapid, Single-Step Protein Encapsulation via Flash NanoPrecipitation

Flash NanoPrecipitation (FNP) is a rapid method for encapsulating hydrophobic materials in polymer nanoparticles with high loading capacity. Encapsulating biologics such as proteins remains a challenge due to their low hydrophobicity (logP < 6) and current methods require multiple processing steps. In this work, we report rapid, single-step protein encapsulation via FNP using bovine serum albumin (BSA) as a model protein. Nanoparticle formation involves complexation and precipitation of protein with tannic acid and stabilization with a cationic polyelectrolyte. Nanoparticle self-assembly is driven by hydrogen bonding and electrostatic interactions. Using this approach, high encapsulation efficiency (up to ~80%) of protein can be achieved. The resulting nanoparticles are stable at physiological pH and ionic strength. Overall, FNP is a rapid, efficient platform for encapsulating proteins for various applications.
ORIGIN AND ROLE OF SOIL VARIABILITY IN SOUTHERN CALIFORNIA CHAPARRAL

Soil heterogeneity can influence ecosystem structure and dynamics. Its origin has been attributed largely to disturbance (physical and biological) or to varying soil genesis factors. In theoretical ecology, spatial heterogeneity is often credited with the maintenance of species diversity, structure, and stability in ecosystems. This study sought to discern the existence, origin, and role of soil variability within chaparral ecosystems of southern California. In 20 randomly chosen chaparral stands, surface (10 cm) soil samples were taken under various canopy shrubs, and species coverage was measured along a 30 m transect. The chaparral stands included those dominated by Adenostoma fasciculatum (chamise), by A, sparsifolium (red shanks), or by a mixture of the two congeners. The order of stands on the first axis of a detrended correspondence analysis (DCA) axis was used in regression analysis to evaluate the trends in soil parameters between the three types of stands. From chamise, through mixed, to red sha...
Examining the influence of outdoor recreation on anthropogenic wildfire regime of the southern Rocky Mountains

Wildfire is a prevalent issue in the southern Rocky Mountains. A large portion of land within the southern Rocky Mountains is federally owned public lands that are extremely prone to wildfire as a result of active wildfire suppression throughout the nineteenth and twentieth centuries. Public lands in the United States were originally created to properly manage natural resources, however, throughout the twentieth century outdoor recreation became increasingly prevalent, providing even greater human access to large volumes of forested public lands. This research analyzes the influence that outdoor recreation and human accessibility have on anthropogenic wildfire occurrence and size on public lands in the southern Rocky Mountains, using San Juan National Forest in southwestern Colorado as the study site. The statistical methodologies of case–control logistic regression analysis, multivariate regression analysis, and descriptive statistics are implemented. Geographic variables are also analyzed to gain a greater understanding of the anthropogenic wildfire regime in this region. Results demonstrate the importance of accessibility on anthropogenic wildfire occurrence and specific activities associated with outdoor recreation that play a major role in directing the pattern of anthropogenic wildfire. The results demonstrate that anthropogenic wildfires occur as a result of activities such as overnight camping in remote portions of the forest, day usage on vehicle trails, and where there are clusters of designated campsites. It is also demonstrated that anthropogenic wildfire pattern is influenced by the geography of the landscape.
A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures.

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.
Variations in tobacco control in National Dental PBRN practices: the role of patient and practice factors

We engaged dental practices enrolled in The National Dental Practice-Based Research Network to quantify tobacco screening (ASK) and advising (ADVISE); and to identify patient and practice -characteristics associated with tobacco control. Dental practices (N = 190) distributed patient surveys that measured ASK and ADVISE. Twenty-nine percent of patients were ASKED about tobacco use during visit, 20% were identified as tobacco users, and 41% reported being ADVISED. Accounting for clustering of patients within practices, younger age and male gender were positively associated with ASK and ADVISE. Adjusting for patient age and gender, a higher proportion of non-whites in the practice, preventive services and proportion on public assistance were positively associated with ASK. Proportion of tobacco users in the practice and offering other preventive services were more strongly associated with ASK and ADVISE than other practice characteristics. Understanding variations in performance is an important step toward designing strategies for improving tobacco control in dentistry.
Natural law in jurisprudence and politics

Introduction 1. Natural law jurisprudence formulated 2. Natural law jurisprudence defended 3. The common good 4. The natural law rejection of consent theory 5. A constant theory of the authority of law 6. The authority of law and legal punishment 7. Beneath and beyond the common good.
Congress ignores the parameters of the health exception. Judicial responses to congressional evidence and partial-birth abortion in Thewake of Stenberg v. Carhart.

Roe v. Wade 1 established a woman's right to undergo a pre-viability abortion and further decided that this right must be balanced with the state's interests in protecting potential life. 2 Perhaps...
IBK (pinkeye) in Black Angus Cattle

Introduction Infectious Bovine Keratoconjunctivitis (IBK), commonly known as pinkeye, is a contagious bacterial disease that affects cattle worldwide. IBK is characterized by excessive tearing, inflammation of the conjunctiva, and ulceration of the cornea. In severe cases, perforation of the cornea may occur, leading to permanent blindness. The incidence rates reported in the ISU beef herd range from 30–52% in the last four years (Figure 1). As a result of the economic impact of pinkeye in the cattle industry, estimated at $150 million/year, the lack of effective treatments against the disease and the increased demand for ‘organic’ products, research in the area of disease resistance is needed. The objectives of our study were: a) to estimate genetic parameters that could aid in the selection of cattle resistant to IBK; b) to evaluate the effects of pinkeye on production traits; and c) to study immunologic factors involved in ocular defense mechanisms.
Understanding and addressing blocking-induced network server latency

We investigate the origin and components of network server latency under various loads and find that filesystem-related kernel queues exhibit head-of-line blocking, which leads to bursty behavior in event delivery and process scheduling. In turn, these problems degrade the existing fairness and scheduling policies in the operating system, causing requests that could have been served in memory, with low latency, to unnecessarily wait on disk-bound requests. While this batching behavior only mildly affects throughput, it severely degrades latency. This problem manifests itself in fairness and service quality degradation, a phenomenon we call service inversion. We show a portable solution that avoids these problems without kernel or filesystem modifications, We modify two different Web servers to use this approach, and demonstrate a qualitatively different change in their latency profiles, generating more than an order of magnitude reduction in latency. The resulting systems are able to serve most requests without being tied to disk performance, and they scale better with improvements in processor speed. These results are not dependent on server software architecture, and can be profitably applied to experimental and production servers.
Onychomycosis due to Exophiala jeanselmei

Summary Background Exophiala jeanselmei is a dematiaceous fungus that may cause invasive diseases, particularly in immunocompromised patients. Most reports mention cutaneous or subcutaneous lesions, and only one case of a nail infected by this fungus has been reported until now. Case report A 39-year-old woman presented a hyperkeratosis and brown coloration of her right big toenail that had continued for two years. On direct examination, E. jeanselmei was observed and then isolated in cultures on repeated samplings from the pathologic nail. Commentary We describe the second case of nail infection due to E. jeanselmei resistant to fluconazole for a one year with no improvement.
Sampling freshwater turtle populations using hoop nets: Testing potential biases

The baited hoop-net is one of the most heavily used sampling tools for monitoring freshwater turtle populations. In the past several years, we have published a series of studies that tested potential biases associated with this sampling method. For this paper, we used a new experiment to directly test the influence of trap-mouth opening size on both captures and escapes. We also summarized the results from previous studies to direct future research on this topic and provide a useful guide for managers and researchers using this sampling device. In our experiment during May 2013 in Texas, USA, we found that traps with larger mouth-openings were more efficient at capturing turtles, while escapes were minimal for both mouth sizes. Thus, at least within the boundaries we tested here, increasing mouth-opening size is an effective way to increase captures without introducing biases caused by differential escape probabilities. © 2014 The Wildlife Society.
Exposure assessment as a tool in regulatory decisions to ensure food safety.

(1983). Exposure Assessment as a Tool in Regulatory Decisions to Ensure Food Safety. Journal of Toxicology: Clinical Toxicology: Vol. 21, No. 1-2, pp. 169-180.
Fixed point set characterizations of Peano continua and absolute retracts

Abstract We extend the notion of absolute fixed point sets to the setting of continuum-valued maps whose point images have small diameters. We demonstrate that the resulting class of spaces ( e -MAFS) coincides with the class of absolute fixed point sets and with the class of absolute retracts in the one-dimensional and planar settings, but that the class of n -dimensional absolute fixed point sets is strictly contained in e -MAFS for all n >1. Moreover, we will give two characterizations for the class of Peano continua in terms of e -MAFS.
Regulation of nocturnal prolactin surges during pregnancy in the rat.

The abrupt termination of the nocturnal PRL surge on day 11 of pregnancy in the rat may be caused by secretions from the uterine-placental unit. Removal of the uterus and its contents on day 6, 8, or 10 of pregnancy prolonged for several days the occurrence of the nocturnal PRL surge, measured at 0300 h. Even after the surge had disappeared in intact pregnant rats, hysterectomy on day 11 or 12 resulted in a resumption of the surge for several days. To determine whether PRL or PRL-like materials would inhibit the surge, bovine PRL or rat placental extract was injected into pregnant rats hysterectomized on day 10. Neither of these two treatments altered serum PRL levels. However, implantation of human placental lactogen into the median eminence on day 8 of pregnancy abruptly terminated the nocturnal PRL surge and caused the pups to be aborted. To determine whether progesterone is responsible for the extended nocturnal PRL surges seen in pregnant rats after hysterectomy, progesterone in silastic tubing was i...
Oxidation of 4-thiouridylate during chromatography on bio-gel.

Abstract The oxidation state of recovered samples of 4-thiouridylate from Bio-Gel P-2 is highly dependent upon the history of the gel. Columns of Bio-Gel that were in contact with the mild oxidizing agent I 2 KI retained an oxidizing potential and oxidized 4-thiouridylate applied in the reduced, sulfhydryl form to the disulfide during chromatography. The oxidizing ability of the gel could be eliminated by treating the column with dithioerythritol, but extensive washing of the gel was essential to prevent the column from then taking on a reducing character.
Dielectrophoretic microfluidic device for the continuous sorting of Escherichia coli from blood cells.

Microfluidic diagnostic devices promise faster disease identification by purifying and concentrating low-abundance analytes from a flowing sample. The diagnosis of sepsis, a whole body inflammatory response often caused by microbial infections of the blood, is a model system for pursuing the advantages of microfluidic devices over traditional diagnostic protocols. Traditional sepsis diagnoses require large blood samples and several days to culture and identify the low concentration microbial agent. During these long delays while culturing, the physician has little or no actionable information to treat this acute illness. We designed a microfluidic chip using dielectrophoresis to sort and concentrate the target microbe from a flowing blood sample. This design was optimized using the applicable electrokinetic and hydrodynamic theories. We quantify the sorting efficiency of this device using growth-based assays which show 30% of injected microbes are recovered viable, consistent with the electroporation of target cells by the dielectrophoretic cell sorters. Finally, the results illustrate the device is capable of a five-fold larger microbe concentration in the target analyte stream compared to the waste stream at a continuous sample flow rate of 35 μl/h.
Neuroscience: an intrusive chaperone.

Stargazin is best known for helping to ferry receptor proteins to the surface of neurons. The discovery that it has an unexpected additional role has widespread implications for the way that neurons talk to each other. Most excitatory synapses in the brain use AMPA receptors, ion channels gated by the neurotransmitter glutamate. Stargazin, a brain-specific transmembrane protein mutated in stargazer epileptic mice, influences AMPA receptors via an effect on trafficking. Now it is shown also to slow channel deactivation and desensitization. Stargazin's cytoplasmic tail controls receptor trafficking, and the ectodomain, the part of the molecule projecting into the extracellular space, controls channel gating. Disrupting the ectodomain's interaction with hippocampal AMPA receptors alters the time course of synaptic responses, establishing a role for stargazin in controlling the brain's synaptic transmissions. These interactions are relevant to disorders such as schizophrenia.
Strong nuclear factor-κB-DNA binding parallels cyclooxygenase-2 gene transcription in aging and in sporadic alzheimer's disease superior temporal lobe neocortex

Cyclooxygenase-2 (COX-2; EC 1.14.99.1) RNA message abundance in 25 control and Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-confirmed sporadic Alzheimer's disease (AD) brains is remarkably heterogeneous when compared with 55 other AD brain RNA message levels that were previously characterized (Lukiw and Bazan: J Neurosci Res 50:937–945, 1997). Examination of nuclear protein extracts (NPXTs) that were derived from control and AD-affected brain neocortical nuclei (n = 20; age range, 60–82 years; postmortem interval, 0.5–6.5 hours) by using gel shift, gel supershift, and cold oligonucleotide competition assay revealed a highly significant relationship between the extent of inflammatory transcription factor, nuclear factor (NF)-κB: DNA binding and the abundance of the COX-2 RNA signal (P 0.045). These data are the first linking inflammation-related transcription factor NF-κB-DNA binding to up-regulation of transcription from a key inflammatory gene, COX-2, in both normally aging brain and in AD-affected neocortex. Systematic deletion of NF-κB-DNA binding sites in human COX-2 promoter constructs attenuates COX-2 transcriptional induction by mediators of inflammation. Strong NF-κB-DNA binding has been reported previously to temporally precede COX-2 gene transcription in human epithelial (A549), hamster B-cell (HIT-T15), human endothelial (HUVEC), human lymphoblast (IM9), human fibroblast (IMR90), rat glioma/mouse neuroblastoma (NG108–15), human keratinocyte (NHEK), mouse fibroblast (NIH 3T3), rat neuroblastoma (SH-SY5Y) cell lines and in mouse and rat brain hippocampus, indicating a highly conserved inflammatory signaling pathway that is common to diverse species and cell types. The mouse, rat, and human COX-2 immediate promoters, despite 7.5 × 107 years of DNA sequence divergence, each retain multiple recognition sites specific for NF-κB-DNA binding. These data suggest that basic gene induction mechanisms, which have been conserved over long periods of evolution, that increase NF-κB-DNA binding may be fundamental in driving transcription from inflammation-related genes, such as COX-2, that operate in stressed tissues, in normally aging cell lines, and in neurodegenerative disorders that include AD brain. J. Neurosci. Res. 53:583–592, 1998. © 1998 Wiley-Liss, Inc.
Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy.

BACKGROUND Although surgery is considered standard therapy for unicentric Castleman disease, favorable responses to radiotherapy also have been documented. The authors undertook this study to analyze the clinical factors, treatment approaches, and outcomes of patients with unicentric or multicentric Castleman disease, and to report the outcomes of patients with unicentric Castleman disease treated with radiotherapy. METHODS The authors reviewed the medical records of 22 patients who had received a histologic diagnosis of Castleman disease at the University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One patient with a concurrent histopathologic diagnosis of nonsecretory multiple myeloma was excluded from the study. In all patients, the diagnosis of Castleman disease was based on the results of lymph node biopsies. Disease was categorized as being either unicentric or multicentric and further subdivided into hyaline vascular, plasma cell, or mixed variant histologic types. Clinical variables and outcomes were analyzed according to treatment, which consisted of surgery, chemotherapy, or radiotherapy. RESULTS Records from 21 patients were analyzed: 12 had unicentric disease, and 9 had multicentric disease. The mean follow-up time for the entire series was 51 months (median, 40 months). Four patients with unicentric disease were treated with radiotherapy alone: 2 remain alive and symptom free, 2 died of causes unrelated to Castleman disease and had no evidence of disease at last follow-up. Eight patients with unicentric disease were treated with complete or partial surgical resection, and all are alive and asymptomatic. All nine patients with multicentric disease were treated with combination chemotherapy: five are alive with no evidence of disease, and four are alive with progressive disease. CONCLUSIONS Surgery results in excellent rates of cure in patients with unicentric Castleman disease; radiotherapy can also achieve clinical response and cure in selected patients. Multicentric Castleman disease is a more aggressive clinical entity and is most effectively treated with combination chemotherapy, whereas the role of radiotherapy in its treatment remains unclear. Cancer 2001;92:670–6. © 2001 American Cancer Society.
Electromyographic findings of paradoxical puborectalis contraction correlate poorly with cinedefecography.

Both intra-anal sponge electromyography (SEMG) and needle electromyography (NEMG) are used to diagnose paradoxical puborectalis contraction (PPC). The aim of this retrospective study was to assess the correlation among SEMG and NEMG and cinedefecography (CD) in the diagnosis of PPC. Between 1992 and 1999, a total of 261 constipated patients underwent both CD and EMG: 64 had NEMG while 197 had SEMG. PPC was diagnosed by EMG when there was failure to achieve a significant decrease in electrical activity of the puborectalis muscle during attempted evacuation. CD criteria for PPC included lack of straightening of the anorectal angle or persistence of the puborectalis impression during evacuation. CD was considered diagnostic and EMG results were thus compared with those of CD. Agreement was calculated using the kappa statistics (κ) for concordance. Both NEMG and SEMG had low positive predictive rates (33% in NEMG, 28% in SEMG) and high negative predictive rates (91% in NEMG, and 78% in SEMG) when correlated with CD findings. Agreement between NEMG and CD was noted in 46 of 64 patients (72%, κ=0.274) while there was agreement between SEMG and CD in 120 of 197 patients (61%; κ=0.067); p>0.05 needle vs. sponge. Although both NEMG and SEMG have a low positive predictive values, they have high negative predictive value for PPC. Therefore, neither NEMG nor SEMG alone are optimal tests for diagnosing the presence of PPC.
The Four-helix Bundle of the Neuronal Target Membrane SNARE Complex Is Neither Disordered in the Middle nor Uncoiled at the C-terminal Region

Assembly of the SNARE complex is an essential step for membrane fusion and neurotransmitter release in neurons. The plasma membrane SNAREs syntaxin 1A and SNAP-25 (t-SNAREs) and the delivery-vesicle SNARE VAMP2 (or v-SNARE) contain the "SNARE regions" that essentially mediate SNARE pairing. Using site-directed spin labeling and EPR distance measurement we show that two identical copies of the SNARE region from syntaxin 1A intertwine as a coiled coil near the "ionic layer" region. The structure of the t-SNARE complex appears to be virtually identical to that of the ternary SNARE complex, except that VAMP2 is substituted to the second copy of syntaxin 1A. Furthermore, it appears that the coiled coil structure is maintained up to residue 259 of syntaxin 1A, identical to that of the ternary complex. These results are somewhat contradictory to the previous reports, suggesting that the t-SNARE complex has the disordered midsection (Xiao, W. Z., Poirier, M. A., Bennett, M. K., and Shin, Y. K. (2001) Nat. Struc. Biol. 8, 308-311) and the uncoiled C-terminal region (Margittai, M., Fasshauer, D., Pabst, S., Jahn, R., and Langen, R. (2001) J. Biol. Chem. 276, 13169-13177). The newly refined structure of the t-SNARE complex provides a basis for the better understanding of the SNARE assembly process. It also provides possible structural-functional clues to the membrane fusion in the v-SNARE deleted fusion models.
Ovarian C17,20-lyase: Changes in intact and hypophysectomized immature rats treated with pregnant mare's serum gonadotropin

Abstract The steroid C17,20-lyase activity of immature rat ovarian microsomal (105,000 g pellet), mitochondrial (10,000 g pellet) and combined fractions was measured using progesterone and 17-hydroxyprogesterone as substrates. Steroid 17α-hydroxylase was measured, using progesterone as substrate, in some of the preparations for comparison. With progesterone about 3.5 times more product (acetic acid) was formed than with 17-hydroxyprogesterone as substrate. The half-time for lyase activity following hypophysectomy was 51.8 h, while that for 17α-hydroxylase was 51.3 h. Following an intravenous injection of 20 iu of pregnant mare's serum gonadotropin (PMS) into immature hypophysectomized rats lyase activity decreased for 12 h followed by recovery during the next 12 h with a rapid increase between 24 and 72 h. In contrast, a subcutaneous injection of the same dose produced an initial rise in activity with a decline between 12 and 24 h, followed by a second large increase. In intact animals injection (s.c.) of PMS produced an initial fall in lyase activity followed by an increase beginning 12 h later. A dramatic decrease in activity occurred between 48 and 72 h concomitant with ovulation; hypophysectomy at 48 h not only prevented the decrease, but produced an increase in activity. The changes in ovarian C17,20-lyase activity following administration of PMS mimic those of 17α-hydroxylase.
The Laser BMD and Other Radiant Energy Weapons: Some Thoughts

This paper opens with a discussion of the ABM Treaty and the particular language in it that presently excludes the deployment of a laser BMD. Eight pressure points are then presented that may cause both the Soviets and the Americans to reevaluate the payoff of such ACD agreements to their overall national security, even to the extent of abrogating the Outer Space Treaty and SALT Phase I. Next an extended presentation of the current state of affairs in the American laser research program is given to show the magnitude of the U. S. commitment to developing radiant energy weapons technology. The paper concludes with a brief excursion into the psychological and strategic systems impact of laser weapons.
COMPARISON OF LINEX AND QUADRATIC BAYES ESTIMATORS FOR THE RAYLEIGH DISTRIBUTION

In this paper, the Bayes estimators for the parameter, the reliability function, and failure rate function of the Rayleigh distribution are obtained when based on complete or type II censored samples. Some types of the linex loss function are used. Comparieons in terms of risks of those under linex loss and squared error loss function with Bayes estimators relative to squared error loss function are made, Numerical example and simulation example are included.
Effects of mold compound material properties on solder reflow package cracking

The phenomenon of package cracking during solder reflow continues to trouble surface mount plastic packages for integrated circuits (ICs). The mechanism has been explained as moisture absorption, vaporization, delamination (loss of adhesion), deformation, and final package cracking. The effect of diminished mold compound material properties in saturated moisture and elevated temperature environments is a crucial factor. Current specifications of flexural strength at room temperature and elevated temperature flexural strengths for mold compounds do not correlate well with known failures during reliability/qualification preconditioning tests. Characterization of mold compound using uniaxial tensile tests have furthered the understanding of the mechanical nature of the material. This paper explains the correlation between mold compound material characterization under tensile load tests and reliability test results. The types of fractures and delaminations that occur during solder reflow appear to be mainly Type I (tensile) in nature for both thick and thin packages (see Figure 1). The contribution of the ductility of the copper leadframe and the hydrostatic pressure within delamination gaps is evident in this tensile gap.
Differentiated Rat Glial Cell Strain in Tissue Culture

Rat glial tumors, induced by injections of N-nitrosomethylurea, were plated and propagated in culture. Among a few cell strains obtained, one clone contains S-100 protein, which is unique to brain in vertebrates. Stationary-phase cultures contain approximately ten times more S-100 protein per cell than exponentially growing cells. When injected into newborn rats, cells producing S-100 grew as a glial tumor, which contained S-100 protein.
Harnessing Chaos in Recurrent Neural Networks

In this issue of Neuron, Sussillo and Abbott describe a new learning rule that helps harness the computational power of recurrent neural networks.
Classification of p-ary self dual quadratic bent functions, p odd ☆

Abstract Let p be an odd prime. We classify all self dual quadratic bent functions from F p n to F p under the action of the orthogonal group O ( n , F p ) . The sizes of the O ( n , F p ) -orbits of such self dual bent functions are explicitly determined. These results are obtained through the following steps: 1. n × n symmetric matrices A over F p satisfying A 2 = c I ( c ∈ F p ⁎ ) are classified under the conjugation by O ( n , F p ) . 2. For each representative A in step 1, the orbits of ker ( A − I ) under the action of cent O ( n , F p ) ( A ) are determined. 3. The sizes of the orbits in steps 1 and 2 are computed.
The development of a crisis management manual for anesthetists and anesthesiologists

Crisis management is part and parcel of anesthesia practice. Cognitive science research and also common sense tell us that no one thinks clearly in a crisis. Taking example from other high-stress occupations, this paper describes the development of an anesthesia crisis management manual, based on data from 4000 anesthesia incidents reported anonymously by practicing anesthetists in Australia and New Zealand. Beginning with a “core algorithm” mnemonic, COVER ABCD A SWIFT CHECK, for routine monitoring and also for rendering any crisis situation “safe,” the anesthetist then chooses 1 of 24 specific, internally validated “sub-algorithms” to diagnose and correct the problem.
Nuclear Detection Instrumentation for Reactivity Measurements with the Fast Flux Test Facility Engineering Mockup Core

Four multichannel detection systems, two operating in an integrated current mode and two in a pulse mode within the engineering mockup core for the Fast Flux Test Facility reactor, successfully furnished signals during a 5-month reactivity surveillance procedures experiment for evaluation of reactivity measurement methods and associated instrumentation for Liquid Metal Fast Breeder Reactor applications. In addition, the adequacy of the low level flux monitor desigin for the Fast Flux Test Facility was verified.
CRITICAL ROLE OF PARATHYROID HORMONE IN FUROSEMIDE-INDUCED NEPHROCALCINOSIS IN THE YOUNG RAT. † 2127

The pathophysiologic mechanism of furosemide (F)-induced nephrocalcinosis(NC) is yet unknown. A few neonates treated with F were reported to developed hyperparathyroidism. To clarify the possible role of parathyroid hormone (PTH) in F-induced NC we studied 26 male 4-wk old Sprague-Dawley rats. They were divided into 4 groups: (a) intact, controls (n=7) (b) intact, treated with F 40 mg/kg I.P., QD (n=7) (c) parathyroidectomized (PTX), controls (n=6) (d) PTX, treated with F as in (b) (n=6). PTX animals were supplemented with 5% Ca gluconate in the drinking water. The study lasted 2 weeks during which animals had free access to water and food. In the last week rats were placed in metabolic cages for urine collection and recording of water and food intake. At the end, rats were anesthetized and exsanguinated. One kidney was studied histologically and the other ashed for Ca determination. Results: There were no differences among the groups with regard to food intake/100 gm animal. Animals in groups (b) and (d) had higher urine output and H2O intake, but less weight gain than groups (a) and (c) respectively, demonstrating the diuretic effect of F. Rats in (b) developed NC with kidney Ca content(μgm/gm dry tissue) 2446±1417 (mean ± SD) compared with (a) 199±39 (p<0.01). Kidney Ca in (c) 249±127 and (d) 178±38 were similar, and they were both significantly lower than (b)(p<0.01) and not different from (a). Similar observations were made on the histologic NC score in which only (b) animals developed NC. Daily Ca excretion in (d) 2361.7±995.4 μgm/100gmBW exceeded that in (b) 818.8±512.1 (p<0.02). Similarly, fractional Ca excretion in (d) 6.63±2.34 was higher than in (b) 1.86±0.84 (p<0.01). Conclusions: (1) PTX protects against F-induced NC, indicating that PTH has as least an important permissive role in the pathophysiology of the phenomenon.(2) Urine Ca per se is not the cause of F-induced NC in this model.
A 1-D Mechanistic Model for the Evolution of Earthflow-Prone Hillslopes

[1] In mountainous terrain, deep‐seated landslides transport large volumes of material on hillslopes, exerting a dominant control on erosion rates and landscape form. Here, we develop a mathematical landscape evolution model to explore interactions between deep‐seated earthflows, soil creep, and gully processes at the drainage basin scale over geomorphically relevant (>10 3 year) timescales. In the model, sediment flux or incision laws for these three geomorphic processes combine to determine the morphology of actively uplifting and eroding steady state topographic profiles. We apply the model to three sites, one in the Gabilan Mesa, California, with no earthflow activity, and two along the Eel River, California, with different lithologies and varying levels of historic earthflow activity. Representative topographic profiles from these sites are consistent with model predictions in which the magnitude of a dimensionless earthflow number, based on a non‐Newtonian flow rheology, reflects the magnitude of recent earthflow activity on the different hillslopes. The model accurately predicts the behavior of earthflow collection and transport zones observed in the field and estimates long‐term average sediment fluxes that are due to earthflows, in agreement with historical rates at our field sites. Finally, our model predicts that steady state hillslope relief in earthflow‐prone terrain increases nonlinearly with the tectonic uplift rate, suggesting that the mean hillslope angle may record uplift rate in earthflow‐prone landscapes even at high uplift rates, where threshold slope processes normally limit further topographic development.
Procedural Sedation by Registered Nurses in the Interventional Radiology Setting: Incorporating Evidence-Based Practice Regarding Medication Selection, Fasting, and Mitigating Cardiorespiratory Complications

Abstract Registered nurses administer procedural sedation in the interventional radiology setting to manage a patient's pain and anxiety to facilitate the performance of unpleasant but necessary procedural interventions in a safe, effective, and humane fashion. The nurse who is administering procedural sedation should maintain competency regarding knowledge of the medications being administered for procedural sedation, knowledge of the drugs required to reverse the effects of procedural sedation medications, ability to assess the patient's response to procedural sedation, and the knowledge and ability to respond appropriately in the event of an adverse reaction to procedural sedation medications. The nurse should be a part of the facility's policymaking team with respect to procedural sedation. The nurse should bring evidence-based information to the policymaking process to assist him/her to be an effective patient advocate. This article examines the available scientific data related to medications for procedural sedation, appropriate fasting considerations, and mitigation of cardiorespiratory complications.
An assessment of two extraordinary speed-readers

An assessment of perceptual and comprehension skills was made on two speed-readers from the American Speedreading Academy who had achieved extraordinary rates of reading. Three experiments were conducted: (1) measurement of perceptual extent for briefly exposed single letters, (2) identification of words within paragraphs under controlled viewing, and (3) text comprehension. The performance of the two speed-readers on the first two tasks was indistinguishable from that of normal readers, although both speed-readers exhibited greater guessing tendencies. On the text comprehension task, the speed-readers were given three opportunities to read a college text and receive an exam given to college students over the same material. Both speed-readers read the text at rates between 15,000 and 30,000 words/min. However, both speed-readers would have failed the exam on each occasion. It was concluded that the only extraordinary talent exhibited by the two speed-readers was their extraordinary rate of page-turning.
Polyelectrolyte effects in DNA condensation by polyamines

Abstract The conditions required for the counterion induced collapse of T7 bacteriophage DNA are briefly reviewed. Using Manning's counterion condensation theory we calculate a striking unity among collapse conditions: collapse occurs when from 89% to 90% of the DNA phosphate charges are neutralized by condensed counterions. The forces involved in collapsed DNA are investigated with emphasis on electrostatic repulsion. It is concluded that polyelectrolyte repulsion is the dominant force opposing collapse. Comparison of the results of polyelectrolyte repulsion calculation made using numerical methods and the Poisson-Boltzmann equation, with values of the attractive energies due to London dispersion interactions, leads to the conclusion that dispersion forces are probably large enough to cause collapse when the repulsions have been reduced by the presence of multivalent counterions.
Stark Level-Crossing Spectroscopy Of Highly Vibrationally Excited Molecules

Stark level-crossing spectroscopy is a new application of pulsed, single-frequency lasers which accesses highly excited vibrational states in a polyatomic molecule. The fluores-cence lifetime of a single rovibrational level in the first excited electronic state (S 1 ) is recorded as it is Stark tuned across highly excited states of the ground electronic state (S 0 ). Resonantly enhanced nonradiative decay causes dips in the S 1 lifetime as the S 1 state passes through resonance with S 0 states, permitting the highly excited So level structure to be mapped out. Stark level-crossing spectra of d 2 -formaldehyde are presented.
Antinociceptive interactions of mu- and kappa-opioid agonists in the colorectal distension assay in rats

Interactions of opioid agonists, fentanyl and oxymorphone (micro-selective) and spiradoline and enadoline(kappa-selective), were examined for additive, sub-additive, or supra-additive antinociception in the colorectal distension (CRD) assay. Single-dose values (mg/kg, 0.006-0.016 for fentanyl, 0.25-1.26 forspiradoline, etc.) were summed to formulate theoretical additive-dose plots for comparison with actual combined-dose effects. Combined fentanyl and spiradoline yielded additive (low-dose levels) or supraadditive(high-dose levels) effects. Single and combined doses of fentanyl (0.012 mg/kg) and spiradoline(0.3 mg/kg) were tested after pretreatment with saline, beta-funaltrexamine (b-FNA, micro-selective antagonist), or nor-binaltorphimine (n-BNI, kappa-selective antagonist). Supra-additive effects of combined agonists were attenuated by either antagonist (greater with n-BNI). But paradoxical patterns of antagonism of single-dose effects occurred: the fentanyl antinociception was not antagonized by b-FNA, whereas the spiradoline antinociception was. The results indicate complex interactions of agonists in this visceral pain model and potential for combined agonists to improve pain relief with decreased side effects
Polymerization of amino acids containing nucleotide bases.

We have prepared the nucleoamino acids 1-(3′-amino, 3′-carboxypropyl)uracil (3) and 9-(3′-amino, 3′-carboxypropyl)adenine (4) as (l)-enantiomers and as racemic mixtures. When3 or4 is suspended in water and treated with N,N′-carbonyldiimidazole, peptides are formed in good yield. The products formed from the (l)-enantiomers are hydrolyzed to the monomeric amino acids by pronase.
Evolution Through Mass Exchange in Close Binary Systems of Total Mass 2.5 M

Calculations show that the observed semi-detached binary systems of mass M 1 + M 2≈ 2.5 M ⊙ can be explained in terms of a mass exchange which starts after the central hydrogen in the original primary has been exhausted.