cssi/SciSciGPT-SciSciNet huggingface dataset:
Muscarinic Stimulation and cGMP Synthesis in the Nervous System

Muscarinic agonists have been shown by several investigators to increase tissue levels of cGMP in the nervous system. Thus, ACh, bethanechol and carbachol raise tissue levels of cGMP in slices of sympathetic ganglion and brain, and in N1E 115 neuroblastoma cells. The increase in cGMP level is 5–10, 2 and 20–200 fold in the three systems, respectively. The effect of muscarinic agonists on cGMP is blocked by atropine and requires the presence of calcium in the medium. Use of the calcium ionophore A23187 leads to large increases in cGMP levels. Depolarization by high K+ of ganglion and brain slices and of neuroblastoma cells also results in elevated cGMP concentrations. These experiments have usually been carried out in the presence of a PDE inhibitor which blocks degradation of cGMP. Therefore, the increased concentrations of the cyclic nucleotide are probably attributable to stimulation of guanylate cyclase, the cGMP synthesizing enzyme, rather than to a decreased degradation of the nucleotide. Guanylate cyclase is present in all three preparations both in membrane-bound and soluble form, with the latter having 2–20 fold higher specific activity. Attempts to show stimulation of guanylate cyclase by muscarinic agonists in broken cell systems have so far been unsuccessful.
Life's Simple 7 and the risk of atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.

Abstract Background and aims We examined the association between the American Heart Association's Life's Simple 7 (LS7) metrics and the risk of atrial fibrillation (AF) in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of adults free of cardiovascular disease (CVD) at baseline. Methods We analyzed data from 6506 participants. The LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose) were each categorized into ideal (assigned 2 points), intermediate (1 point) or poor (0 points). Scores were summed for a maximum of 14. A score of 0–8 was considered inadequate; 9-10, average and 11-14, optimal for cardiovascular health. Atrial fibrillation was ascertained using ICD-9 codes from hospital discharge records and Medicare claims data. Cox proportional hazard ratios (HR) and incidence rates of AF per 1000 person-years were calculated. Results During a median follow-up of 11.2 years (interquartile range: 10.6–11.7 years), 709 (11%) participants were hospitalized with a first AF episode. In the overall cohort, optimal scores at baseline were associated with a 27% lower risk for AF compared with inadequate scores (0.73 [0.59–0.91]). A similar finding was observed when the results were stratified by race/ethnicity (White, Chinese American, African American and Hispanic), though many of the associations were not statistically significant. There was no interaction by race/ethnicity (p = 0.15). Conclusions In the overall cohort, optimal LS7 status was associated with a lower risk of AF. These findings suggest that promoting ideal cardiovascular health may reduce the incidence and burden of AF.
Genetics of classic von Willebrand's disease. II. Optimal assignment of the heterozygous genotype (diagnosis) by discriminant analysis

In classic von Willebrand's disease (vWd), assignment of the heterozygous genotype for genetic studies and diagnosis for clinical purposes (which are not exactly the same) are formidable problems. We have pointed out in the first report in this series that almost 50% of the members of two large kindred who transmitted this disease, and were therefore heterozygous, were scored as normal by the usual tests of hemostasis. This report describes how this large proportion can be significantly reduced by application of discriminant analysis. Using linear discriminants in three variables--coagulation factor VIII (VIII:C), factor-VII-related antigen (VIIIR:Ag), and the ristocetin cofactor related to factor VIII (VIIIR:WF)--we were able to classify as heterozygous more than 80% of the transmitters in the two large kindred. It was of particular interest that the four parents of two related vWd homozygotes could be scored as heterozygous by discriminant analysis even though all their laboratory tests were within the normal ranges.
Let's Keep Women in Microwaves (But Let's Turn Down the Heat)

Reports on the problems and issues concerning the ability to retain and encourage women to enter and build careers in the science, technology, engineering, and math (STEM) fields.
An anomaly detection framework for dynamic systems using a Bayesian hierarchical framework

Abstract Complex systems are susceptible to many types of anomalies, faults, and abnormal behavior caused by a variety of off-nominal conditions that may ultimately result in major failures or catastrophic events. Early and accurate detection of these anomalies using system inputs and outputs collected from sensors and smart devices has become a challenging problem and an active area of research in many application domains. In this article, we present a new Bayesian hierarchical framework that is able to model the relationship between system inputs (sensor measurements) and outputs (response variables) without imposing strong distributional/parametric assumptions while using only a subset of training samples and sensor attributes. Then, an optimal cost-sensitive anomaly detection framework is proposed to determine whether a sample is an anomalous one taking into consideration the trade-off between misclassification errors and detection rates. The model can be used for both supervised and unsupervised settings depending on the availability of data regarding the behavior of the system under anomaly conditions. The unsupervised model is particularly useful when it is prohibitive to identify in advance the anomalies that a system may present and where no data are available regarding the behavior of the system under anomaly conditions. A Bayesian hierarchical setting is used to structure the proposed framework and help with accommodating uncertainty, imposing interpretability, and controlling the sparsity and complexity of the proposed anomaly detection framework. A Markov chain Monte Carlo algorithm is also developed for model training using past data. The numerical experiments conducted using a simulated data set and a wind turbine data set demonstrate the successful application of the proposed work for system response modeling and anomaly detection.
Real-world clinical outcomes and toxicity in metastatic breast cancer patients treated with palbociclib and endocrine therapy

Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to improve progression-free survival (PFS) when combined with letrozole or fulvestrant in phase 3 clinical trials. We evaluated real-world outcomes in metastatic breast cancer patients who received palbociclib in combination with endocrine therapy in routine clinical practice. Records of patients with advanced hormone receptor (HR)-positive breast cancer treated with palbociclib at the Cleveland Clinic health system from February, 2015 to December, 2017 were retrospectively reviewed. The primary end point was PFS. In this cohort, 411 women were included. The median age and follow-up times were 53.5 years and 10.2 months, respectively. The median PFS for palbociclib plus letrozole was 15.1 months for patients treated in first line, 10.5 months in second line, and 4.2 months in third line and beyond. For patients who received fulvestrant plus palbociclib, the median PFS in first, second, and third line and beyond were 11.6, 12.3, and 6.4 months, respectively. The most common adverse events were hematologic, with grade 3–4 neutropenia occurring in 58% of patients. Thirty-one (8%) patients permanently discontinued palbociclib due to adverse events. Among patients with HR-positive advanced breast cancer, the estimated PFS in patients treated with fulvestrant and palbociclib was comparable to a previously reported phase 3 trial. However, the median PFS with letrozole and palbociclib was shorter than previously reported data from phase 2 and 3 trials. Palbociclib toxicity was very manageable, with a low drug discontinuation rate.
Defining the spectrum of spasticity-associated involuntary movements.

Abstract Background Spasticity can be associated with several hyperkinetic involuntary movements generally referred to as “spasms” despite different phenomenology and clinical characteristics. Objective To better characterize the phenomenology and clinical characteristics of spasticity-associated involuntary movements. Methods We performed a cross-sectional study of a consecutive patient sample from the spasticity clinic. Each patient was interviewed by a movement-disorder neurologist who conducted a standardized movement-disorder survey and a focused exam. Patients with involuntary movements were video-recorded and videos were independently rated by a separate blinded movement-disorder neurologist. Results Sixty-one patients were included (54% female, mean age 49.7 ± 13.9 years). Of the entire cohort, 11.5% had spinal, 44.3% had cerebral, and 44.3% had mixed-origin spasticity. Fifty-eight patients (95%) reported one or more involuntary movements: 75% tonic spasms (63% extensor, 58% isometric, 41% flexor/adductor), 52% spontaneous clonus, 34% myoclonus, 33% focal dystonia, and 28% action tremor. One third of the involuntary movements were painful. Only 53% of patients reported that their involuntary movements were much or very-much improved with their current anti-spasticity management. Patients treated with intrathecal baclofen therapy were more likely to report much or very-much improvement compared to patients receiving oral and/or botulinum therapy (P = 0.0061 and 0.0069 respectively). Conclusion Most spastic patients experience spasticity-associated involuntary movements of variable phenomenology and impact. However, only half of these patients experience significant improvement with the current management strategies. More research is needed to explore better treatment options for spasticity-associated involuntary movements with focus on phenomenology-specific approaches.
Acute coronary artery obstruction following surgical repair of congenital heart disease

Abstract Objectives Acute coronary artery obstruction is a rare complication of congenital heart disease surgery but imposes a high burden of morbidity and mortality. Previous case series have described episodes in specific congenital heart lesions or surgical repairs but have not examined the complication in all-comers to congenital heart surgery. We hypothesize that shorter time from a clinically recognized postoperative sentinel event suggestive of coronary ischemia to diagnosis of coronary obstruction is associated with improved clinical outcomes. Methods This was a single-center, retrospective review of patients diagnosed with acute coronary artery obstruction by angiography following surgical repair of congenital heart disease between January 2000 and June 2016. Results In total, 34 patients were identified. The most common procedures associated with coronary artery obstruction were the Norwood procedure, arterial switch operation, and aortic valve repair/replacement. In total, 79% required mechanical circulatory support, 41% died, and 27% were listed for heart transplant. Patients who died or were listed for heart transplant had longer median sentinel-event-to-cardiac-catheterization time (28 [6-168] hours vs 10 [3-56] hours, P = .001), and longer median sentinel-event-to-intervention time (32 [11-350] hours vs 13 [5-59] hours, P = .003). Patients with hypoplastic left heart syndrome were at greater risk of death or transplant listing (odds ratio, 9.23, P = .03). Conclusions Time from clinically relevant postoperative sentinel event to diagnosis of coronary artery obstruction by angiography was associated with transplant-listing-free survival. Clinicians should maintain a high index of suspicion for coronary obstruction and consider early catheterization and coronary angiography for patients in whom post-operative coronary compromise is suspected.
Structural Characteristic Measure based Data Driven Coherence Identification of Generators using PMU Measurements

Generators coherence identification is critical to ensure transient stability after controlled islanding and to develop dynamic equivalents for stability studies of large complex power system. This paper presents a novel approach for data driven coherence identification of generators using Phasor Measurement Unit (PMU) data and its structural characteristic measures. Unlike alternatives which cannot handle missing data due to their dependency on a distance metric for similarity evaluation, the proposed novel method relies on global characteristic measures extracted from PMU time series data, to determine coherency. Weighted approach is used to integrate these extracted measures into a Cumulative Characteristic Measure (CCM). Pearson correlation coefficient is applied on this cumulative characteristic measure to identify coherent generators (CGs). Western Interconnection power system in North America (WECC-179) is utilized to validate and demonstrate the effectiveness of the proposed data-driven coherency identification method.
Frederic Bastiat: Public Choice Theorist

Frederic Bastiat is best known for his popularizing of economic ideas in pamphlets like That Which is Seen, and That Which is Not Seen, The Law, and The State, as well as his books Economic Sophisms and Economic Harmonies. However, he was also an economic theorist, a fact that gets lost in the midst of his fiery pamphlets. Examining his correspondences and early political and economic writing, I show how he began developing public choice insights into rent seeking, voter rationality, and the behavior of legislators that would anticipate scholarship that would come a century later.
Identifying Pedestrian Crash Contributing Factors using Association Analysis and Their Implications for Development of Active Pedestrian Safety System

An active pedestrian safety system (APSS) would be more effective by considering the implications of crash contributing factors. In addition, the APSS needs to be tested and evaluated in the field;...
Decoding the 2D IR spectrum of the aqueous proton with high-level VSCF/VCI calculations

The aqueous proton is a common and long-studied species in chemistry, yet there is currently intense interest devoted to understanding its hydration structure and transport dynamics. Typically described in terms of two limiting structures observed in gas-phase clusters, the Zundel H5O2+ and Eigen H9O4+ ions, the aqueous structure is less clear due to the heterogeneity of hydrogen bonding environments and room-temperature structural fluctuations in water. The linear infrared (IR) spectrum, which reports on structural configurations, is challenging to interpret because it appears as a continuum of absorption, and the underlying vibrational modes are strongly anharmonically coupled to each other. Recent two-dimensional IR (2D IR) experiments presented strong evidence for asymmetric Zundel-like motifs in solution, but true structure–spectrum correlations are missing and complicated by the anharmonicity of the system. In this study, we employ high-level vibrational self-consistent field/virtual state configuration interaction calculations to demonstrate that the 2D IR spectrum reports on a broad distribution of geometric configurations of the aqueous proton. We find that the diagonal 2D IR spectrum around 1200 cm−1 is dominated by the proton stretch vibrations of Zundel-like and intermediate geometries, broadened by the heterogeneity of aqueous configurations. There is a wide distribution of multidimensional potential shapes for the proton stretching vibration with varying degrees of potential asymmetry and confinement. Finally, we find specific cross peak patterns due to aqueous Zundel-like species. These studies provide clarity on highly debated spectral assignments and stringent spectroscopic benchmarks for future simulations.
Infrastructure Enabled Autonomy—Autonomy as a Service

Multiple studies have established the potential for significant societal, environmental and economic benefits from autonomous vehicles. However, all the current approaches to autonomous driving require the automotive manufacturers to shoulder the primary responsibility and liability associated with replacing human perception and decision making with automation, slowing the penetration of autonomous vehicles, and consequently slowing the realization of the benefits of autonomous vehicles. We propose a new approach to autonomous driving that will re-balance the responsibility and liabilities associated with autonomous driving between traditional automotive manufacturers, private infrastructure players, and third-party players. The proposed distributed intelligence architecture leverages recent advances in connectivity and edge computing. The resulting Infrastructure Enabled Autonomy (IEA) leads to the new business model of “autonomy as a service”.
Christian Realism and the State as Idol: Feminist and Postcolonial Critique and Christian Realist Theology in an Interdependent World

At a time of outspoken nationalism, Christian realism accurately diagnoses idolatry of the state as a political and theological problem. The power of sovereign states protects self-determination bu...
Auditory joint attention skills: Development and diagnostic differences during infancy

To date, joint attention skill assessments have focused on children's responses to multimodal bids (RJA) and their initiation of bids (IJA) to multimodal spectacles. Here we gain a systematic view of auditory joint attention skills using a novel assessment that measures both auditory and multimodal RJA and IJA. In Study 1, 47 typically developing (TD) children were tested 5 times from 12 to 30 months to document auditory joint attention skill development. In Study 2, 113 toddlers (39 TD, 33 autism spectrum disorder [ASD], and 41 non-ASD developmental disorders [DD]; average age 22.4 months) were tested to discern the effects of ASD. Our findings fit well within the established depiction of joint attention skills with one important caveat: auditory items were far more difficult to execute than multimodal ones. By 24 months, TD children passed multimodal RJA items at the near-ceiling level, an accomplishment not reached even by 30 months for auditory RJA items. Intentional communicative IJA bids also emerged more slowly to auditory spectacles than to multimodal spectacles. Toddlers with DD outperformed toddlers with ASD on multimodal RJA items but toddlers in both groups rarely passed any auditory RJA items. Toddlers with ASD often monitored their partner's attention during IJA items, albeit less often than toddlers with DD and TD toddlers, but they essentially never produced higher-level IJA bids, regardless of modality. Future studies should investigate further how variations in bids and targets affect auditory joint attention skills and probe the relation between these skills and language development.
Radiocarpal Dislocation: ORIF

Radiocarpal dislocations are rare, but serious injuries. The shearing and rotation forces associated with these injuries lead to extrinsic carpal ligament damage and associated fractures of the distal radius and carpus. Prompt reduction and stabilization via surgical repair are critical to providing satisfactory outcomes. These injuries are often complex and are associated with variable injury patterns of osseous, ligamentous, and soft tissues. Knowledge and comfort with multiple surgical approaches and repair techniques can help the surgeon achieve better outcomes.
The use of EPA assessments in decision-making: Do supervision ratings correlate with other measures of clinical performance?

Entrustable professional activities (EPAs) have been introduced as a framework for teaching and assessment in competency-based educational programs. With growing use, has come a call to examine the...
Teaming in the contemporary fertility clinic: creating a culture to optimize patient care

When a diverse group of individuals is working together in the contemporary fertility clinic to provide time-sensitive and complex care for patients, a high degree of coordination and collaboration must take place. When performed dynamically, this process is referred to as teaming. Although the positive impact of teamwork in health care settings has been well established in the literature, the concept of teaming has limited foundation in the clinic. This review will provide an overview of how teaming can be used to improve patient care in today's fertility clinics. Approaches to integrating teaming into the clinic that will be discussed include framing, the creation of a psychologically safe environment for staff input, and facilitating collaborative constructs to support teaming. Best practices to implement teaming and how to address challenges to teaming in today's clinical environment will also be addressed.
Religion, Violence, and Emotion: Modes of Religiosity in the Neolithic and Bronze Age of Northern China

This paper explores the development of religious traditions in the Neolithic and Bronze Age of northern China. It applies the cognitive anthropological theory of Divergent Modes of Religiosity (DMR) for the first time in this part of the world. DMR theory frames ritual behavior in two distinct modes, one that is more traumatic/emotional and occurs less frequently (imagistic rituals) and another that is more placid and occurs more frequently (doctrinal rituals). Various archaeological and historic sources indicate that violent imagistic rituals involving human sacrifice and feasting began deep in the Neolithic; but religion did not become more tame when societies entered the Bronze Age, as predicted by DMR theory. Instead, violent imagistic rituals continued and became arguably more brutal. The application of DMR theory here is a useful means to explore the challenging topic of religious violence and to reveal biases in the treatment of ritual and religion in Shang studies.
Leaky humanitarianism: the anthropology of small arms control in the Gambia

Among Gambians, attitudes toward small arms control vary. For some, it appears as the unjust act of an overbearing and autocratic government; for others, it is part of the project of fashioning a modern state; for yet others, being licensed to carry a gun is a sign of respect from the state. On the basis of these differences, I develop the notion of “leaky humanitarianism” to capture how humanitarian small arms control underwrites state power. I further suggest that small arms control should be understood as a form of statecraft centered on injuring power and is thus a potent but underused diagnostic in the anthropology of the state. [small arms control, the state, humanitarianism, the Gambia, hunters, precarity, bureaucracy]
Effect of d-Penicillamine on Poliovirus Replication In HeLa Cells

Abstract A series of mercaptan compounds were studied with respect to their ability to inhibit the growth of poliovirus in cultured cells. Of the compounds tested only d-penicillamine possessed antiviral activity. There was no direct effect on the virus itself, nor were the processes of adsorption, penetration and uncoating, or virus-induced “shut-off” of host cell protein synthesis inhibited. At concentrations where there was no effect on host cell RNA or protein synthesis, d-penicillamine caused a marked inhibition of virus-specific RNA and protein synthesis. Although much reduced, the relative concentrations of single-stranded and double-stranded viral RNA synthesized in the presence of d-penicillamine was unchanged. Similarly, all apparent precursor and cleavage product proteins could be synthesized in the presence of the drug. The inhibitory effect was reversible, after a lag of 1.5 to 2 h after removal of the drug, and normal yields of virus could be obtained. The structural and functional properties of d-penicillamine are discussed in relation to requirements for anti-polioviral activity.
Development of a tier 1 R5 clade C simian–human immunodeficiency virus as a tool to test neutralizing antibody‐based immunoprophylaxis

Background While some recently transmitted HIV clade C (HIV-C) strains exhibited tier 1 neutralization phenotypes, most were tier 2 strains (J Virol 2010; 84:1439). Because induction of neutralizing antibodies (nAbs) through vaccination against tier 2 viruses has proven difficult, we have generated a tier 1, clade C simian–human immunodeficiency virus (SHIV-C) to permit efficacy testing of candidate AIDS vaccines against tier 1 viruses. Methods SHIV-1157ipEL was created by swapping env of a late-stage virus with that of a tier 1, early form. Results After adaptation to rhesus macaques (RM), passaged SHIV-1157ipEL-p replicated vigorously in vitro and in vivo while maintaining R5 tropism. The virus was reproducibly transmissible intrarectally. Phylogenetically, SHIV-1157ipEL-p Env clustered with HIV-C sequences. All RM chronically infected with SHIV-1157ipEL-p developed high nAb titers against autologous as well as heterologous tier 1 strains. Conclusions SHIV-1157ipEL-p was reproducibly transmitted in RM, induced cross-clade nAbs, and represents a tool to evaluate anti-HIV-C nAb responses in primates.
A Four-Dimensional View of Assembly of a Morphogenetic Protein during Sporulation in Bacillus subtilis

We report the use of a fusion to the green fluorescent protein to visualize the assembly of the morphogenetic protein SpoIVA around the developing forespore during the process of sporulation in the bacterium Bacillus subtilis. Using a deconvolution algorithm to process digitally-collected optical sections, we show that SpoIVA, which is synthesized in the mother cell chamber of the sporangium, assembled into a spherical shell around the outer surface of the forespore. Time-lapse fluorescence microscopy showed that this assembly process commenced at the time of polar division and seemed to continue after engulfment of the forespore was complete. SpoIVA remained present throughout the late stages of morphogenesis and was present as a component of the fully mature spore. Evidence indicates that assembly of SpoIVA depended on the extreme C-terminal region of the protein and an additional region that directly or indirectly facilitated interaction among SpoIVA molecules. The N- and C-terminal regions of SpoIVA, including the extreme C terminus, are highly similar to the corresponding regions of the homologous protein from the distantly related endospore-forming bacterium Clostridium acetobutylicum, attesting to their importance in the function of the protein. Finally, we show that proper localization of SpoIVA required the expression of one or more genes which, like spoIVA, are under the control of the mother cell transcription factor ςE. One such gene was spoVM, whose product was required for efficient targeting of SpoIVA to the outer surface of the forespore.
Engineering Customized TALE Nucleases (TALENs) and TALE Transcription Factors by Fast Ligation‐Based Automatable Solid‐Phase High‐Throughput (FLASH) Assembly

Customized DNA-binding domains made using transcription activator-like effector (TALE) repeats are rapidly growing in importance as widely applicable research tools. TALE nucleases (TALENs), composed of an engineered array of TALE repeats fused to the FokI nuclease domain, have been used successfully for directed genome editing in various organisms and cell types. TALE transcription factors (TALE-TFs), consisting of engineered TALE repeat arrays linked to a transcriptional regulatory domain, have been used to up- or downregulate expression of endogenous genes in human cells and plants. This unit describes a detailed protocol for the recently described fast ligation-based automatable solid-phase high-throughput (FLASH) assembly method. FLASH enables automated high-throughput construction of engineered TALE repeats using an automated liquid handling robot or manually using a multichannel pipet. Using the automated approach, a single researcher can construct up to 96 DNA fragments encoding TALE repeat arrays of various lengths in a single day, and then clone these to construct sequence-verified TALEN or TALE-TF expression plasmids in a week or less. Plasmids required for FLASH are available by request from the Joung lab (http://eGenome.org). This unit also describes improvements to the Zinc Finger and TALE Targeter (ZiFiT Targeter) web server (http://ZiFiT.partners.org) that facilitate the design and construction of FLASH TALE repeat arrays in high throughput.
Pediatric Granular Cell Tumor of the Breast: A Case Report and Review of the Literature

Objective. Granular cell tumors arise from neurogenic mesenchymal stem cells and can occur anywhere throughout the body. They rarely present as breast masses and should be included in the differential diagnosis of pediatric breast neoplasms. We report a rare presentation of a pediatric breast granular cell tumor and a review of the literature. Participant. A 15-year-old female presented with an enlarging breast mass. She underwent ultrasound imaging and excisional biopsy, which revealed a granular cell tumor. Granular cell tumors of the breast are difficult to diagnose using ultrasound and mammography due to numerous similarities to other breast masses. Histopathologic staining best differentiates breast granular cell tumors from other breast masses with their positive staining for S100, CD68, and neurospecific enolase. Conclusion. Although rare, granular cell tumors of the breast should be considered as a possible diagnosis for pediatric breast masses to allow for proper management and follow-up for these patients. Although rare, these tumors do have malignant potential necessitating a correct and timely diagnosis.
Are shunt series and shunt patency studies useful in patients with shunted idiopathic intracranial hypertension in the emergency department

Abstract Objectives Shunt series and shunt patency studies can be performed in the emergency department (ED) to evaluate for shunt malfunction in patients with idiopathic intracranial hypertension (IIH). Here, we examine the utility of these studies in this specific patient population. Methods We retrospectively reviewed the ED visits of all shunted patients diagnosed with IIH from 2003 to 2014. ED visits for symptoms not related to the patient's IIH were excluded from the study. Collected variables included demographics, symptoms, IIH diagnosis and treatment history, imaging findings, and management changes. Results Twenty-five (81%) patients had a total of 105 visits involving a shunt series, with four (3.9%) showing problems with the catheter. The majority of shunt series ( n = 101, 96%) showed no catheter pathology. Based on results of the shunt series alone, in 3 instances, management changes in the form of shunt revision or shunt reprogramming occurred. Of the 105 visits with a shunt series, 17 (16%) resulted in a change in management as compared to 12 out of 66 (18%) visits without a shunt series ( p = 0.83). Nine patients had a total of 10 visits involving a shunt patency study: five were normal, four were abnormal, and one was inconclusive. Based on findings on the shunt patency study alone, changes in management leading to shunt adjustment or revision occurred in 4 instances. Of the 10 visits with shunt patency studies, 5 resulted in a change in management as compared to 24 out of 161 visits without a shunt patency study ( p = 0.014). Conclusions Shunt series detected catheter pathology only 3.9% of the time, and there was no difference in the rate of management changes between those patients who underwent a shunt series and those who did not. There was a significant difference in the rate of management changes in patients who received shunt patency studies as compared to those who did not. Shunt series may not be a useful screening tool to be used universally to diagnose shunt malfunction in IIH patients in the ED, and should be utilized when there is concern for impending visual loss. Shunt patency studies should be reserved for patients with inconclusive diagnostic imaging and clinical findings to decide whether to proceed to surgical exploration and revision.
Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations

Summary X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common of the ectodermal dysplasias, results in the abnormal development of teeth, hair, and eccrine sweat glands. The gene responsible for this disorder, EDA1, was identified by isolation of a single cDNA that was predicted to encode a 135–amino-acid protein. Mutations in this splice form were detected in EDA1 gene ( Tabby [ Ta ]) allowed us to identify a second putative isoform of the EDA1 protein (isoform II) in humans. This EDA1 cDNA is predicted to encode a 391-residue protein, of which 256 amino acids are encoded by the new exons. The putative protein is 94% identical to the Ta protein and includes a collagen-like domain with 19 repeats of a Gly-X-Y motif in the presumptive extracellular domain. The genomic structure of the EDA1 gene was established, and the complete sequence of the seven new exons was determined in 18 XLHED-affected males. Putative mutations, including 12 missense, one nonsense, and four deletion mutations, were identified in ∼95% of the families. The results suggest that EDA1 isoform II plays a critical role in tooth, hair, and sweat gland morphogenesis, whereas the biological significance of isoform I remains unclear. Identification of mutations in nearly all of the XLHED families studied suggests that direct molecular diagnosis of the disorder is feasible. Direct diagnosis will allow carrier detection in families with a single affected male and will assist in distinguishing XLHED from the rarer, clinically indistinguishable, autosomal recessive form of the disorder.
Ca2+-Regulatory Function of the Inhibitory Peptide Region of Cardiac Troponin I is Aided by the C-Terminus of Cardiac Troponin T: Effects of FHC Mutations Ctni R145G and Ctnt R278C, Alone and in Combination, on Filament Sliding

Investigations of cardiomyopathy mutations in Ca2+ regulatory proteins troponin and tropomyosin provide crucial information about cardiac disease mechanisms, and provide insights into functional domains in the affected polypeptides. Hypertrophic cardiomyopathy-associated mutations TnI R145G, located within the inhibitory peptide (Ip) of human cardiac troponin I (hcTnI), and TnT R278C, located immediately C-terminal to the IT arm in human cardiac troponin T (hcTnT), share remarkable features: structurally, biochemically, and pathologically. Using bioinformatics, we find compelling evidence that affected regions of hcTnI and hcTnT, may be related_not just structurally_but also evolutionarily. Because alignment of TnI and TnT coincides with the known structure of the IT-arm, and both Arg mutations are located close to the C-terminal end of the IT-arm, we investigated functional relationships between hcTnI R145G and hcTnT R278C. We hypothesized that if the mutations affected function independently, then their effects would be additive in a double mutant complex. We characterized Tn complexes containing either mutation alone, or both mutations simultaneously, using in vitro motility assays run with varying [Ca2+], temperature, or HMM density. Our most significant findings show that TnT R278C "rescued" some deleterious effects of TnI R145G at high Ca2+, but exacerbated the loss of function (i.e., switching off the actomyosin interaction) at low Ca2+. Taken together, our results raise the likelihood that cTnI's Ip sequence might share a common evolutionary origin with, and thus be structurally and functionally related to, the C-terminus of cTnT. In accord with this prediction, our experimental results suggest that the C-terminus of cTnT aids Ca2+-regulatory function of cTnI Ip within the troponin complex.
Spin-Based Computing: Device Concepts, Current Status, and a Case Study on a High-Performance Microprocessor

As the end draws near for Moore's law, the search for low-power alternatives to complementary metal–oxide–semiconductor (CMOS) technology is intensifying. Among the various post-CMOS candidates, spintronic devices have gained special attention for their potential to overcome the power and performance limitations of CMOS. In particular, all spin logic (ASL) technology, which performs Boolean operations and transfers the output in the spin domain, has been proposed for enabling new capabilities—such as high density, low device count, and nonvolatility—that were previously impossible with CMOS technology. In this paper, first we provide an overview of the history and the current status of the various spintronic devices being pursued by the research community. Then, we describe how spin-based components are integrated into a computing system and the advantages that result. We use a hypothetical spintronic-based Intel Core i7 as a test vehicle to compare the system-level power requirements of ASL- and CMOS-based systems, taking into consideration the unique demands of spin-based interconnects. We conclude with a brief analysis of current limitations and future directions of spintronic research.
Comment on Determination of Nuclear Quadrupole Interactions: Copper-Doped Rutile

A complete diagonalization of the spin Hamiltonian is necessary to obtain consistent principal values of the nuclear quadrupole coupling tensor from $\ensuremath{\Delta}{M}_{I}=0$ and $\ensuremath{\Delta}{M}_{I}=\ifmmode\pm\else\textpm\fi{}2$ lines in EPR spectra. As an example, proper recalculation for Ti${\mathrm{O}}_{2}$: ${\mathrm{Cu}}^{++}$ shows greatly revised values, ${Q}^{\ensuremath{'}}\ensuremath{\approx}0.0010$ ${\mathrm{cm}}^{\ensuremath{-}1}$, $\ensuremath{\eta}\ensuremath{\approx}0.1$.
Optimum-forced current for electrical linewidth measurements of submicron features

Specific forced currents are required for different materials and feature sizes to ensure the best measurement precision and to minimize Joule heating. The determination of the optimum forced current depends on several parameters: sheet resistance, doping level, feature aspect ratio, and arm length/width of the van der Pauw (VDP) structure. A test of several different materials, resistivities, and feature sizes shows that the optimum forced current in the bridge and the VDP structures can be determined by simple empirical equations. The affect of Joule heating in a 0.2 micrometers structure was also evaluated. When supplied a forced current above the critical current density, the initial voltage reading is 9% larger than the initial voltage reading with the optimum forced current. There was no obvious Joule heating effect below the critical current density. In the extreme case an optimum forced current applied to a 0.22 micrometers structure for as long as 10 minutes produced a voltage rise exponentially to only 0.2% of the normalized voltage measured at the beginning.
Progress and prospects for optimum antiarrhythmic drug design

Different class I drugs slow down to differing degrees the rate at which sodium channel availability, hence excitability, recovers after action potentials. Drugs that produce longer recovery half-times generally produce greater proarrhythmic side effects. Increased lipid solubility may improve a drug's “potency” for blocking channels yet with implications for adverse effects. Drug action may be potentiated in depolarized and acidotic tissue via modulation of the recovery process. A knowledge of molecular properties of antiarrhythmic drugs helps to define these modes of interraction with the sodium channels and, hence, will help in future drug design. Prospects for improving our understanding of ionic events involved in the repolarization phase of cardiac action potentials are also outlined. The development of successful strategies for controlling reentrant arrhythmias will probably require a thorough understanding of both class I and class III drug actions at the level of the membrane ion channel.
The Question of Namibia

A review of some of the legal and political problems which have arisen in the context of the United Nations relating to the administration and responsibility for Namibia as it moves to become an independent country.
Groups with infinite virtual cohomological dimension which act freely on Rm×Sn−1

In this paper free and proper discontinuous actions on Rm × Sn − 1 are constructed of groups with infinite virtual cohomological dimension.
Connection between the bremsstrahlung tip and direct radiative recombination: angular distributions and polarization correlations

We illustrate the possibility for calculation of bremsstrahlung tip angular destributions and polarization correlations from corresponding photoeffect results with an extension of the method for connecting bremsstrahlung tip and direct-radiative-recombination (DRR) cross sections developed by Lee and Pratt. The agreement between results obtained with this method and results from our numerical partial-wave calculations is, in general, satisfactory. We note features of the distributions and correlations, and once again point out the inadequacies of the nonrelativistic dipole approximation for the evaluation of bremsstrahlung or DRR angular distributions.
Predictive value of a 1-day, 1-eye trial on the 1-month ocular hypotensive response of latanoprost 0.005%

Abstract PURPOSE: To determine if a 1-day, 1-eye trial of latanoprost 0.005% was predictive of the 1-month intraocular pressure response in patients with uncontrolled open-angle glaucoma on maximally tolerated medical therapy without latanoprost. METHODS: One eye of 39 consecutive patients was enrolled in prospective trial of latanoprost 0.005%. An investigator masked to treatment eye and intraocular pressure result measured intraocular pressure at 1 day and 1 month after treatment. The diagnostic precision of the 1-day, 1-eye trial for the 1-month result was determined at a 10%, 20%, and 30% reduction from baseline intraocular pressure. RESULTS: Treatment produced a mean ± SD (range) decrease in intraocular pressure from 20.9 ± 4.6 (14 to 35) mm Hg to 16.6 ± 3.6 (9 to 26) mm Hg at 24 hours ( P t test). This reduction in intraocular pressure was similar at 1 month with mean ± SD (range) intraocular pressure of 16.1 ± 3.1 (9 to 22) mm Hg ( P t test). The accuracy of the 1-day, 1-eye trial for the 1-month response at a 10%, 20%, and 30% reduction of intraocular pressure from baseline intraocular pressure was 96% (chi square=29.5, P P = .004), and 80% (chi square=10.2, P = .001), respectively. CONCLUSION: A 1-day, 1-eye trial of latanoprost 0.005% is predictive of the 1-month intraocular pressure response in patients with uncontrolled open-angle glaucoma.
The Starr valve revisited

Abstract Nearly 30 years have elapsed since Dr Starr's publication introducing the Starr-Edwards valve. Despite reputed difficulties with a ball-and-cage prosthesis, Starr's dedication in developing this concept has resulted in a valve that today continues to be a benchmark of longevity and function.
Role of the Critical Voltage Effect in Materials Characterization

The HVEM “critical voltage” effect can provide quantitative information about intrinsic crystal parameters that cannot be obtained easily on a microscopic scale by other techniques. For pure elements, more accurate atomic scattering amplitudes and Debye temperatures have been determined. In binary alloys, the occurrence of segregation, short or long range order or clustering can be evaluated and charge distribution or transfer and atomic bonding changes detected in favorable cases.
Chiral surfaces and metal/ceramic heteroepitaxy in the Pt/SrTiO3(621) system

Abstract Low-energy electron diffraction (LEED), atomic force microscopy (AFM), and X-ray diffraction (XRD) have been used to investigate the structural and morphological character of a naturally chiral ceramic SrTiO3(621) substrate and of Pt and Cu thin films deposited on its surface. AFM experiments showed that as-received chirally-oriented SrTiO3(621) substrates display atomically smooth surface morphologies, while LEED patterns revealed that the surface structure has a net chirality. Pt(621) and Cu(621) thin films were grown heteroepitaxially on SrTiO3(621) substrates, as confirmed by XRD. AFM showed that the film surfaces were atomically smooth and LEED illustrated that the Pt films exhibit surface chirality, and by implication that the atomically-flat chirally-oriented Cu films also have chiral surfaces. The characteristics of the observed LEED patterns, where splitting of diffraction spots is considered to arise from the kinked step features of naturally chiral fcc metal surfaces, are discussed with respect to existing models. These results indicate that the chiral SrTiO3(621) ceramic surface drives the growth of single-enantiomer, chiral, metal (621) thin films.
Acute Oxygen in Patients with Sleep Apnea and COPD

Nocturnal oxygen administered to patients with disordered breathing ameliorates hypoxemia. As a result, an important chemical stimulus to arousal is diminished. This could cause prolongation of disordered breathing events, worsen respiratory acidosis, and induce potentially harmful cardiac arrhythmias. The presence of chronic obstructive pulmonary disease (COPD) could further aggravate the situation since such patients may have depressed hypercarbic responses. To test this hypothesis, 20 obese men with sleep apnea and COPD were studied polysomnographically on two nights receiving air on one or oxygen at 4 L/min on the other. Supplemental oxygen increased mean DOB event duration from 25.7 to 31.4 seconds (p
Sequence patterns in the resolution of clinical instabilities in community-acquired pneumonia and association with outcomes.

BACKGROUND In patients hospitalized with community-acquired pneumonia (CAP), indicators of clinical instability at discharge (fever, tachycardia, tachypnea, hypotension, hypoxia, decreased oral intake and altered mental status) are associated with poor outcomes. It is not known whether the order of indicator stabilization is associated with outcomes.
Effect of nitrous oxide on cerebral blood velocity while reclining and standing

Cerebral blood velocity (CBV) (measured with transcranial Doppler, TCD) and other physiological and rating scale indices were measured before, during, and after inhaling a mixture of 40% nitrous oxide/oxygen and 40% nitrogen/oxygen, given during two separate visits in 7 normal male volunteers. During nitrous oxide/oxygen but not nitrogen/oxygen inhalation, CBV and euphoria increased significantly with minimal changes in other physiological indices except an increase in pulse rate after nitrous oxide/oxygen. In another 7 male volunteers, similar measurements were obtained while lying down and standing up during nitrous oxide/oxygen mixture and nitrogen/oxygen mixture inhalations, given during two separate visits. Nitrous oxide/oxygen inhalation produced significant CBV increase, which showed nonsignificant decrease of no clinical significance during standing up. There were no significant postural changes in blood pressure. Standing up during nitrous oxide/oxygen inhalation was associated with significant though mild dizziness.
NBTI model development with regression analysis

In industry, negative bias temperature instability (NBTI) mechanism degradation models are derived from regression analysis of stress data. The model exponents vary for different technologies and manufacturers. We will show that limited sampling (using only one lot) and the misapplication of regression analysis are major contributors to the variation in model coefficients. Linearizing a nonlinear equation by taking logarithms will give more emphasis to smaller values and less to larger values.