cssi/SciSciGPT-SciSciNet huggingface dataset:
A CRISPR toolbox for generating intersectional genetic mice for functional, molecular, and anatomical circuit mapping

ABSTRACT Background A full understanding of circuits and cellular mechanisms governing health and disease requires the dissection and multi-faceted study of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic response alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical study. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, the expense and difficulty associated with production of customized intersectional mouse lines have limited widespread application to more common allele manipulations that are often commercially produced at great expense. Results We present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production. Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study how functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase- responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle. Conclusions Lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.
Photomask challenges for data-centric computing in the 2020s

The world is rapidly shifting towards data-centric computing model with significant growth in compute, storage and networking. Moore’s law scaling to reduce power, improve performance and reduce area and cost per transistor to support data centric growth places significant challenges for photomask process, control, and metrology. DUV lithography continues to be workhorse technology and continues to drive innovation. Multiple solutions are being developed to solve DUV mask challenges associated with a big die requirement. While DUV production is being projected to be strong for next few years, EUV is picking up pace and being deployed in high volume manufacturing. EUV is an opportunity-rich environment for improvements and innovations that will continue to advance the journey. EUV HiNA is a major step in the lithography paradigm where 0.55 NA EUV optics will enable a shift to sub-10nm resolution. The HiNA mask ecosystem will adapt by growing the newly created low NA EUV supply chain into new directions. The photomask environment will continue to bring creativity, drive innovations and gain commercial rewards.
Pregnancy Diagnosis by Rectal Palpation in Dairy Cows

Pregnancy diagnosis by rectal palpation is one of the most frequent procedures performed by dairy veterinarians, but very little is known about the economically optimal schedule for palpation. In a practitioner survey, 34 days was the median response for how soon after breeding veterinarians reported routinely palpating cows (see companion abstract). Previous research showed that cows checked later in gestation were more likely to stay in the herd and calve again, but those studies did not address the optimal herd-level schedule. The purpose of this study was to estimate the effect of palpation schedule on days open and culling for four pregnancy diagnosis schedules in herds using only artificial insemination for breeding.
Fabrication and field emission properties of vertical, tapered GaN nanowires etched via phosphoric acid.

The controlled fabrication of vertical, tapered, and high-aspect ratio GaN nanowires via a two-step top-down process consisting of an inductively coupled plasma reactive ion etch followed by a hot, 85% H3PO4crystallographic wet etch is explored. The vertical nanowires are oriented in the[0001]direction and are bound by sidewalls comprising of{336¯2}semipolar planes which are at a 12° angle from the [0001] axis. High temperature H3PO4etching between 60 °C and 95 °C result in smooth semipolar faceting with no visible micro-faceting, whereas a 50 °C etch reveals a micro-faceted etch evolution. High-angle annular dark-field scanning transmission electron microscopy imaging confirms nanowire tip dimensions down to 8-12 nanometers. The activation energy associated with the etch process is 0.90 ± 0.09 eV, which is consistent with a reaction-rate limited dissolution process. The exposure of the{336¯2}type planes is consistent with etching barrier index calculations. The field emission properties of the nanowires were investigated via a nanoprobe in a scanning electron microscope as well as by a vacuum field emission electron microscope. The measurements show a gap size dependent turn-on voltage, with a maximum current of 33 nA and turn-on field of 1.92 V nm-1for a 50 nm gap, and uniform emission across the array.
Comparison of Coronary Artery Involvement and Mortality in STEMI Patients With and Without SARS-CoV-2 During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

Abstract Introduction : Cardiovascular injury with SARS-CoV-2 infection is well known. Several studies have outlined baseline characteristics in patients presenting with STEMI and SARS-CoV-2. Paucity in data exists in selective coronary involvement in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. Methods : A systematic search and meta-analysis of studies meeting the inclusion and exclusion criteria obtained from MEDLINE, Scopus, and Cochrane databases was performed utilizing PRISMA criteria. The main outcome was likelihood of coronary artery involvement among patients with STEMI and SARS-CoV-2 versus without SARS-CoV-2. The primary adverse outcome measured was in-hospital mortality. Results : The final analysis included 5 observational studies with a total of 2, 266 patients. There was no statistical significance in LM (OR 1.40; 95% CI: 0.68, 2.90), LAD (OR 1.09; 95% CI 0.83, 1.43), LCX (OR 1.17; 95% CI: 0.75, 1.85), or RCA (OR 0.59; 95% Confidence Interval 0.30, 1.17) disease among the two groups. LAD disease was the most prevalent coronary involvement among patients with STEMI and SARS-CoV-2 (49.6%). Higher in-hospital mortality was observed in the STEMI and SARS-CoV-2 group (OR 5.24; 95% Confidence Interval 3.63, 7.56). Discussion : Our analysis demonstrated no statistical significance in selective coronary involvement in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. The higher mortality among patients with SARS-CoV-2 and STEMI has been noted in prior studies with concerns being late presentation due to fear of infection, delayed care time, and poor resource allocation. Focus should be placed on identifying and managing comorbidities to reduce mortality.
Bartleby the Absurd

Those who have read Moby Dick have seen the way Ahab anticipates the modern hero in his existential anguish, in his protest against man's condition and man's fate, his demand for reasons, his rage against finding himself a personality "in the midst of the personified impersonal," a rational being at the mercy of irrational forces he can neither understand nor control. And in "Bartleby the Scrivener," Melville once again runs ahead of his time, for Bartleby is a metaphysical rebel exhibiting what Camus has called "an absurd sensitivity"— that is, an awareness of the "absurd."
Imaging sensor noise as digital X-ray for revealing forgeries

In this paper, we describe a new forensic tool for revealing digitally altered images by detecting the presence of photo-response nonuniformity noise (PRNU) in small regions. This method assumes that either the camera that took the image is available to the analyst or at least some other nontampered images taken by the camera are available. Forgery detection using the PRNU involves two steps - estimation of the PRNU from non-tampered images and its detection in individual image regions. From a simplified model of the sensor output, we design optimal PRNU estimators and detectors. Binary hypothesis testing is used to determine which regions are forged. The method is tested on forged images coming from a variety of digital cameras and with different JPEG quality factors. The approximate probability of falsely identifying a forged region in a non-forged image is estimated by running the algorithm on a large number of non-forged images.
Structural Features Determining Differential Receptor Regulation of Neuronal Ca Channels

Dihydropyridine-insensitive Ca channels are subject to direct receptor G-protein-mediated inhibition to differing extents. alpha1B channels are much more strongly modulated than alpha1E channels. To understand the structural basis for this difference, we have constructed and expressed various alpha1B and alpha1E chimeric Ca channels and examined their regulation by kappa-opioid receptors. Replacement of the first membrane-spanning domain of alpha1E with the corresponding region of alpha1B resulted in a chimeric Ca channel that was modulated by kappa-opioid receptors to a significantly greater extent than alpha1E. Transfer of the N terminus and I/II loop from alpha1B in addition to domain I resulted in a chimeric channel that was modulated to the same extent as alpha1B. Other regions of the molecule do not appear to contribute significantly to the degree of inhibition obtained, although the C terminus may contribute to facilitation.
Composite mirror replication: curing, coating and polishing

The quickest method for generating a lightweight composite optic is to replicate an optical quality glass tool onto a carbon fiber reinforced polymer (CFRP). However, the effects of fiber print-through create an unacceptable surface roughness on replicated CFRP mirrors. In order to mitigate fiber print-through, two methods of generating a polishable resin layer were investigated. The first method employs the application of resin films to the CFRP surface. The second, unconventional method generates a co-cured resin layer using a magnetic fiber migration approach. A final polishing step was used to attain optical quality surface features on all of the replicated specimens. Replicated resin films with thicknesses ≥ 0.25 mm sufficiently mitigate fiber print-through. Room temperature and high temperature cure resins were polished below 50 A rms surface roughness (1 μm to 1mm bandwidth) or better. The magnetic fiber migration technique was suitable for eliminating fiber print-through. Replicated magnetic fiber laminates were polished to within specular quality as well.
Relative amplitude of aspiration noise as a voicing cue for syllable-initial stop consonants.

The present experiments demonstrate that amplitude of aspiration noise (relative to the following periodic portion of the vowel) is a cue for the distinction between voiced and voiceless syllable-i...
Adopting multi-valued logic for reduced pin-count testing

The reduced pin-count test (RPCT) has been proposed for testing cost reduction in various scenarios like scan, test compression and multi-site test. In this paper, we propose a new RPCT technique in which several digital signals are combined into a single multi-valued logic (MVL) signal. Mixed-signal components, digital-to-analog and analogto- digital converters, are used to compress the tester channels and then to expand the test at the circuit under test. The method allows greater bandwidth efficiency than the existing SerDes alternative. However, the MVL signal can be sensitive to noise and nonlinearity errors. To ensure the reliability of test application, we provide an error control scheme. The paper gives theoretical analysis as well as experimental evidence.
Alzheimer Disease and Other Dementias

Dementia is a common problem seen by family physicians. There is no disease-modifying agent currently available for treating progressive dementias such as Alzheimer’s. Cognitive-enhancing medications can be offered on a trial basis but have very limited benefit. Management should focus initially on patient and family education and early discussion of goals of care. Physicians should look to evidence-based guidelines to help provide high-value interventions for the prevention and management of common complications of dementia. These include depression, delirium, agitation, falls, adverse medication effects, and burdensome, distressing interventions near the end of life. Advanced dementia can be devastating for both the patient and family. Support from a trusted family physician during this difficult time can be invaluable. Approach to Care: Older adults should undergo routine cognitive screening in venues such as the Medicare Wellness Visit. Screening can be done through a number of available tools including the MiniCog (3-item 5-min recall and clock draw) [1]. If the initial screening is abnormal, a more detailed, quantifiable test such as the Montreal Cognitive Assessment (MoCA) or the Mini-Mental Status Exam (MMSE) should be considered. These are more widely accepted as reliable for tracking disease progression and statistical responses to treatment. Evaluation for reversible causes of cognitive impairment should also be done (Table 1). If this is negative, it is highly probable that the patient suffers from one of the common non-reversible dementias. A consultation should be considered if the diagnosis is in doubt.
Adding Valid Time to XPath

In this paper we extend the XPath data model and query language to include valid time. XPath is a language for specifying locations within an XML document. We extend XPath's data model by adding to each node a list of disjoint intervals or instants that represents the valid time. The valid time for a node is constrained to be a subset of the valid time for a node's parent. We extend the XPath query language with an axis to access nodes in a valid-time view of the valid time for a node. The view is a calendar-specific formatting of the valid time in XML. By rendering the time in XML, we can reuse nontemporal XPath to extract the desired information within a valid-time axis. The extension is fully backwards-compatible with XPath.
A simulation application in facility expansion decision-making

A manufacturing company wanted to expand its capacity to produce plastic parts. The expansion could cost several million dollars. To decide how many plastic molding presses should be purchased, a computer simulation study was conducted. The object of the study was to find the quantity and type of equipment needed to satisfy production requirements in a just-in-time environment. The model of the plastic molding operation was used to study the effects of lot-size variation, scheduling changes and equipment alternatives on work-in-process, change-over costs, and make-span. Several scenarios were simulated and compared from which the suitable quantity and type of equipment were determined. >
Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway

Despite recent advances in diagnosis and management, prostrate cancer remains the second most common cause of death from cancer in American men, after lung cancer. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in patients with castration-resistant prostate cancer (CRPC). Currently, the androgen inhibitors enzalutamide and abiraterone are approved for treatment of metastatic CRPC. Here we show for the first time that both enzalutamide and abiraterone render prostate tumor cells more sensitive to T cell-mediated lysis through immunogenic modulation, and that these immunomodulatory activities are androgen receptor (AR)-dependent. In studies reported here, the NAIP gene was significantly down-regulated in human prostate tumor cells treated in vitro and in vivo with enzalutamide. Functional analysis revealed that NAIP played a critical role in inducing CTL sensitivity. Amplification of AR is a major mechanism of resistance to androgen-deprivation therapy (ADT). Here, we show that enzalutamide enhances sensitivity to immune-mediated killing of prostate tumor cells that overexpress AR. The immunomodulatory properties of enzalutamide and abiraterone provide a rationale for their use in combination with immunotherapeutic agents in CRPC, especially for patients with minimal response to enzalutamide or abiraterone alone, or for patients who have developed resistance to ADT.
Operative Management of Lung Injuries

The need for operative management of pulmonary injury is uncommon. However, delaying patients requiring a thoracotomy for trauma increases morbidity and mortality; thus, the key aspect in management in this patient population is timely an operative intervention. Once the decision is made to perform a thoracotomy, the goal is to obtain control of hemorrhage as soon as possible. Lung lacerations from penetrating trauma usually have a tract though the pulmonary parenchyma and are usually amenable to lung-sparing techniques such as tractotomy or limited resections. Injuries from blunt trauma usually result in more significant tearing of the lung and are more likely to require larger resections. With modern approach to resuscitation, it is more important to quickly control hemorrhage than to worry about removing “too much lung.” Damage control techniques including temporary hilar clamping and chest packing are useful adjuncts to achieve survivorship in those patients with extensive chest trauma.
Methodological Synthesis in Quantitative L2 Research: A Review of Reviews and a Case Study of Exploratory Factor Analysis

Research synthesis and meta-analysis provide a pathway to bring together findings in a given domain with greater systematicity, objectivity, and transparency than traditional reviews. The same techniques and corresponding benefits can be and have been applied to examine methodological practices in second language (L2) research (e.g., Plonsky, 2013). In the first half of this paper, we integrate findings, trends, and critiques from a number of syntheses to both illustrate the potential of this approach and to promote more methodologically informed research practices. Our emphasis here is on study designs and sampling practices. In the second half, we provide an example of a methodological synthesis that reviews the use of one particular statistical technique as applied in L2 research: exploratory factor analysis (EFA). Here and throughout the chapter, we provide specific recommendations for primary research as well as for future efforts to synthesize methodological practices in the field.
The Role of Counterterrorism Law in Shaping Ad Bellum Norms for Cyber War

Most cyber-intrusions now and in the foreseeable future will take place outside the traditional consensus normative framework for uses of force supplied by international law. For the myriad, multi-layered and multi-faceted cyber-attacks that disrupt but do not destroy, whether state-sponsored or perpetrated by organized private groups or single hacktivists, much work remains to be done to build a normative architecture that will set enforceable limits on cyber intrusions and provide guidelines for responses to disruptive cyber-intrusions. In this paper, my interest is directed at a subset of those cyber-attacks – those where terrorists are responsible or attribution is not known but points in terrorists’ direction, and where the effects are very disruptive but not sufficiently destructive to cross the traditional LOAC and Charter self-defense thresholds. For this subset of cyber attacks, counterterrorism law may offer a useful complementary normative supplement to LOAC and the Charter. Especially over the last decade, a corpus of counterterrorism law has evolved as domestic and international law in response to transnational terrorism. In contrast to the dominant pre-September 11 conception that countering terrorism involved either the use of military force or enforcement of the criminal laws, counterterrorism law now incorporates a diverse range of responses to terrorism, many of which are borrowed, sometimes in modified form, from existing international and domestic law. Based on a maturing international legal regime, this article concludes that over time and through state practice, along with legal, strategy and policy development in the international community a set of counterterrorism law norms for cyber war could emerge.
Glutamic Acid Decarboxylation in Chlorella

The decarboxylation of endogenous free glutamic acid by Chlorella pyrenoidosa, Marburg strain, was induced by a variety of metabolic poisons, by anaerobic conditions, and by freezing and thawing the cells. The rate of decarboxylation was proportional to the concentration of inhibitor present. Possible mechanisms which relate the effects of the various conditions on glutamate decarboxylation and oxygen consumption by Chlorella are discussed.
Consequences of envenomation: red imported fire ants have delayed effects on survival but not growth of native fence lizards

Context Aggressive encounters, including those with venomous species, impose selective pressure on native species. Immediate lethal outcomes of these encounters have been the primary focus of research in this field. However, not all aggressive interactions result in immediate mortality, and indirect consequences of aggressive interactions may be an equally important but under-considered selective force. The red imported fire ant is a globally important venomous invader that imposes novel selective pressure on native communities. Aims We examined indirect effects of fire ant envenomation on native fence lizard growth rates and subsequent survival. Methods Fence lizards are subject to fire ant envenomation in the field when they eat fire ants (they are stung inside the mouth) and through fire ant attack (they are stung on the body). We quantified body sizes of adult lizards from fire ant-invaded and uninvaded sites. We then experimentally exposed hatchling fence lizards to the two modes of fire ant envenomation, and quantified their growth and survival over 1 year. Key results Lizards from fire ant-invaded sites were smaller than those from an uninvaded site, even at similar latitudes. However, in contrast to studies on other native taxa, we found no effect of fire ant venom on growth rates of lizards from naive or fire ant-invaded populations. Lizards exposed to fire ant venom, through both eating and attack, experienced higher rates of delayed mortality, with 34% of lizards dying 1–11 weeks post-envenomation compared with 12% of lizards in the control treatment. These patterns were true for fire ant naive populations as well as those exposed to fire ants for ~35 generations. Conclusions These results suggest that the smaller body sizes observed in fence lizards from fire ant-invaded sites are not a consequence of exposure to fire ant venom. However, fence lizards from both sites suffer delayed survival costs of fire ant envenomation. Implications The present study highlights the importance of considering indirect fitness consequences of aggressive encounters if we are to fully understand the ecological and evolutionary consequences of these interactions, and adequately manage and predict the impacts of invasive species.
Update on the challenges facing the adult with congenital heart disease community: for both the patient and provider.

Purpose of review The success in the management of congenital heart disease has resulted in a growing population now expected to reach adulthood. The declining mortality during childhood results in adults with decades of cardiovascular disease burden. The purpose of this review is to provide an update on some of the common issues encountered when caring for the adult with congenital heart disease through a review of recently published articles. Recent findings This review focuses on addressing the lack of information, gaps in clinical care, single ventricle complications, and heart failure in the adults with congenital heart disease population. Summary The advancing age of the congenital heart population comes with a substantial life cardiovascular risk. Despite this, they typically experience and report a good quality of life. Providing care to adults with congenital heart disease requires a comprehensive team to address the many complications that are known to arise. This comprehensive team should be available to all.
Leniency and post-cartel market conduct: Preliminary evidence from parcel tanker shipping

Abstract This paper provides preliminary observations from data involving a cartel in the international maritime shipping of chemicals. These data provides a setting in which to consider how the presence of a cartel affects market conduct following its dissolution and, in turn, how this might be affected by the obligations imposed on firms who seek leniency. The patterns in the data are consistent with cartel distortions persisting in the post-cartel period, possibly due to the presence of long-term contracts. An implication is that, in addition to terminating involvement in cartel activity, some social benefit may accrue from requiring firms seeking leniency to mitigate the harm caused by cartel actions.
Applied chemistry: Molecules meet materials

An inorganic semiconductor can take the place of the liquid electrolyte typically used in dye-sensitized solar cells. This achievement points the way to making these devices more easily manufactured and more stable. See Letter p.486 The efficiency and low cost of dye-sensitized solar cells based on titanium dioxide make them attractive for renewable-energy applications, but the use of organic electrolytes in the device structures renders them susceptible to leakage and corrosion. Mercouri Kanatzidis and colleagues have now identified a solution-processable inorganic semiconductor consisting of CsSnI3- xFx compounds that can replace the liquid electrolyte, yielding all-solid-state solar cells with impressive energy-conversion efficiencies, especially in the red region of the spectrum, where they outperform conventional dye-sensitized solar cells. These new compounds consist of inexpensive, Earth-abundant elements and can be processed at room temperature. With further optimization and improved dyes, much higher efficiencies should be achievable.
Flow Velocity Measurements Using ChERS in the HSX Stellarator

A Charge Exchange Recombination Spectroscopy (ChERS) system has been used to measure the velocity, density, and temperature profiles of fully stripped carbon impurities in the Helically Symmetric eXperiment (HSX). Velocity measurements have been obtained by reversing the magnetic field between sets of shots in order to reverse the plasma flow velocity. This essentially doubles the Doppler shift of the measured photons. It also eliminates the need to accurately determine the exact wavelength of the unshifted emission line which can depend on plasma conditions. Because two viewing angles are used for each radial location, the velocity magnitude and direction can be determined. The intrinsic velocity is found to move primarily in the direction of quasihelical symmetry with a peak velocity ∼20 km/s. The velocity increases with increasing ECRH power (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Technology Adoption in Small Family-Owned Businesses: Accessibility, Perceived Advantage, and Information Technology Literacy

The purpose of the study was to examine the antecedents and impacts of information technology (IT) adoption by small family-owned businesses, using data from the National Family Business Survey. This research tested a model based on the Diffusion of Innovations framework and the Technology Acceptance Model (TAM). Family business managers’ prior knowledge and level of IT use, business location, and community size/type were important antecedents to the decision to adopt IT. Ease of use and decision to adopt IT accounted for over 60% of the variance in usefulness of IT and implementation of internet and IT capabilities. The implementation of IT capabilities accounted for nearly 40% of the variance in actual use of IT and perceived impact of the internet.
Factors associated with sleep disturbance among older adults in inpatient rehabilitation facilities.

Purpose The purpose of this article is to provide an overview of changing sleep patterns and common sleep disorders in older adults and to discuss treatment options of sleep disturbances within inpatient rehabilitation facilities (IRFs). Methods Through extensive review of the existing literature, common sleep disorders among older adults and several key factors that may impact sleep in older adults in inpatient rehabilitation facilities, such as behavioral and environmental factors, psychosocial and emotional factors, medical conditions, and medications were identified. Findings Current literature on the factors associated with sleep disturbance in older adults in IRFs is based on work with community-dwelling older adults and those in long-term care facilities. While interventions to address these disorders and research investigation key factors associated with sleep problems among older adults appear in the literature, there is very little work that applies these interventions within IRFs. Conclusions and Clinical Relevance Research is needed to examine the impact of sleep problems on older adults in IRFs, including work that focuses on intervention trials to identify successful treatments for these problems and translate those approaches into practice.
Interface wear reactions between nickel and a nickel-33 at. % chromium alloy in a simulated face seal

Abstract The wear tracks of a nickel specimen mated against a nickel-33 at. % chromium alloy in a simulated face seal have been characterized by optical and scanning electron microscopy. Both surfaces showed a smeared layered appearance, with smooth-bottomed holes present. A layer of alloy material was transferred to the nickel, but no nickel was transferred to the alloy. Observations of a cross section through the nickel specimen revealed that the alloy layer covering the surface was highly plastically deformed. The layer of nickel in contact with the alloy layer had a fine grain size, showing that frictional heating had induced recrystallization in the nickel, although not in the alloy layer.
Retinoic Acid Inhibition of Hyaluronate Synthesis in Cultured Human Skin Fibroblasts

The effects of all-trans retinoic acid on glycosaminoglycan (GAG) accumulation were determined in cultured primary human skin fibroblasts. Confluent cultures treated with retinoic acid accumulated less [3H]GAG than those without the compound, an effect with an apparent threshold of 10 nM which was dose dependent in the concentration range tested (0–10 μM). At 10 μM, the inhibition was 54%. Greater than 80% of the labeled macromolecular material was streptomyces hyaluronidase digestible in cultures labeled with [3H]acetate. The incorporation of H2[35S]O4 into chondroitin sulfate and dermatan sulfate was unaffected, as was total protein synthesis. Retinol also inhibited accumulation of [3H]GAG, but was far less potent. T3 and dexamethasone can inhibit [3H]hyaluronate synthesis. When retinoic acid was added to cultures treated with either of these hormones at concentrations that maximally inhibit [3H] GAG accumulation, there was a further decrease in the rate of macromolecular accumulation. The retinoic acid...
Dopamine Modulation of Avoidance Behavior in Caenorhabditis elegans Requires the NMDA Receptor NMR-1

The nematode C. elegans utilizes a relatively simple neural circuit to mediate avoidance responses to noxious stimuli such as the volatile odorant octanol. This avoidance behavior is modulated by dopamine. cat-2 mutant animals that are deficient in dopamine biosynthesis have an increased response latency to octanol compared to wild type animals, and this defect can be fully restored with the application of exogenous dopamine. Because this avoidance behavior is mediated by glutamatergic signaling between sensory neurons and premotor interneurons, we investigated the genetic interactions between dopaminergic signaling and ionotropic glutamate receptors. cat-2 mutant animals lacking either the GLR-1 or GLR-2 AMPA/kainate receptors displayed an increased response latency to octanol, which could be restored via exogenous dopamine. However, whereas cat-2 mutant animals lacking the NMR-1 NMDA receptor had increased response latency to octanol they were insensitive to exogenous dopamine. Mutants that lacked both AMPA/kainate and NMDA receptors were also insensitive to exogenous dopamine. Our results indicate that dopamine modulation of octanol avoidance requires NMR-1, consistent with NMR-1 as a potential downstream signaling target for dopamine.
An Open Trial of Olanzapine in Anorexia Nervosa

Background: Recent reports raise the possibility that olanzapine can assist weight gain and improve behavioral symptoms during refeeding in anorexia nervosa. Method: Seventeen DSM-IV anorexia nervosa subjects hospitalized between May 1999 and October 2000 were enrolled in open-label treatment with olanzapine for up to 6 weeks. Baseline weight and symptoms were compared to patients' status at the end of treatment. Results: Olanzapine administration was associated with a significant reduction in depression, anxiety, and core eating disorder symptoms, and a significant increase in weight. A comparison with our historical data suggests that subjects in this study had a significantly greater decrease in depression. Conclusion: These data lend support to the possibility that olanzapine may be useful in treating anorexia nervosa. However, a controlled trial is necessary to demonstrate that olanzapine is efficacious.
ZONAL PARAMETRIC IMAGING: CONCEPT AND APPLICATION TO RENAL ANGIOGRAPHY;

A new method is described that modifies the original concept of parametric or functional imaging. While the conventional parametric image replaces a temporal sequence of images with a single static image based upon a selected parameter, in the new approach fixed zonal areas and bands are established within the imaged organ, and the mean value for each zone is computed. It is shown that parametric images can be quantified and objectively compared in this way. The algorithm has been implemented to analyze renal studies.
Perceptual models of viewpoint preference

The question of what are good views of a 3D object has been addressed by numerous researchers in perception, computer vision, and computer graphics. This has led to a large variety of measures for the goodness of views as well as some special-case viewpoint selection algorithms. In this article, we leverage the results of a large user study to optimize the parameters of a general model for viewpoint goodness, such that the fitted model can predict people's preferred views for a broad range of objects. Our model is represented as a combination of attributes known to be important for view selection, such as projected model area and silhouette length. Moreover, this framework can easily incorporate new attributes in the future, based on the data from our existing study. We demonstrate our combined goodness measure in a number of applications, such as automatically selecting a good set of representative views, optimizing camera orbits to pass through good views and avoid bad views, and trackball controls that gently guide the viewer towards better views.
Polysiloxanes : a paradigm or paradox since the 1960's

For poly(TMPS) a fractions and blends of fractions, it has been established experimentally that the isothermal spherulitic growth rate, G, and physical properties are strongly interrelated. Correlations also depend strongly upon molecular weight. Below the melt viscosity entanglement molecular weight M c , G is very dependent upon molar mass whenever crystallized fractions are chain folded, brittle and lacking in tie-molecules. Above M c , G is essentially constant, and polymers are tough and durable because of trapped entanglements, tie-molecules and the like, that are mostly located at lamellar interfaces. Growth rate measurements and other physical properties of poly(TMPS) are inconsistent with the claim that reptation is a viable process in the crystallization of this polymer. Selective chemical etching of poly(TMPS) crystal surfaces of moderate MW (35 × 10 3 Daltons) show an increase in crystallinity from 75% to 95% as the surface is removed, thus testifying to a less than ordered surface morphology. Notably, in melt crystallized high MW fractions, approaching 10 6 Daltons and beyond, the morphology is much less well organized than it is in moderate to low MW fractions. Trends in the physical properties of polyethylenes, polyisoprene and poly(ethylene oxide) MW fractions are analogous in behavior to melt crystallized poly(TMPS) fractions over comparable molecular weights ranges, and consistent with a morphology that is dependent upon polymer chain length.
A Comparison Study of Plantar Foot Pressure in a Standardized Shoe, Total Contact Cast, and Prefabricated Pneumatic Walking Brace:

Total contact casting is the current recommended treatment for Wagner Stage 1 and 2 neuropathic plantar ulcers. The rationale for this treatment includes the equalization of plantar foot pressures and generalized unweighting of the foot through a total contact fit at the calf. Total contact casting requires meticulous technique and multiple cast applications to avoid complications before ulcer healing. An alternative to total contact casting is the use of a prefabricated brace designed to maintain a total contact fit. This study compares plantar foot pressure metrics in a standardized shoe (SS), total contact cast (TCC), and prefabricated pneumatic walking brace (PPWB).Five plantar foot sensors (Interlink Electronics, Santa Barbara, CA) were placed at the first, third, and fifth metatarsal heads, fifth metatarsal base, and midplantar heel of 10 healthy male subjects. Each subject walked at a constant speed over a distance of 280 meters in a SS, PPWB, and TCC. A custom-made portable microprocessor-based sy...
Linkage Detection Adaptive to Linkage Disequilibrium: The Disequilibrium Maximum-Likelihood–Binomial Test for Affected-Sibship Data

It has been demonstrated in the literature that the transmission/disequilibrium test (TDT) has higher power than the affected-sib-pair (ASP) mean test when linkage disequilibrium (LD) is strong but that the mean test has higher power when LD is weak. Thus, for ASP data, it seems clear that the TDT should be used when LD is strong but that the mean test or other linkage tests should be used when LD is weak or absent. However, in practice, it may be difficult to follow such a guideline, because the extent of LD is often unknown. Even with a highly dense genetic-marker map, in which some markers should be located near the disease-predisposing mutation, strong LD is not inevitable. Besides the genetic distance, LD is also affected by many factors, such as the allelic heterogeneity at the disease locus, the initial LD, the allelic frequencies at both disease locus and marker locus, and the age of the mutation. Therefore, it is of interest to develop methods that are adaptive to the extent of LD. In this report, we propose a disequilibrium maximum-binomial-likelihood (DMLB) test that incorporates LD in the maximum-binomial-likelihood (MLB) test. Examination of the corresponding score statistics shows that this method adaptively combines two sources of information: (a) the identity-by-descent (IBD) sharing score, which is informative for linkage regardless of the existence of LD, and (b) the contrast between allele-specific IBD sharing score, which is informative for linkage only in the presence of LD. For ASP data, the proposed test has higher power than either the TDT or the mean test when the extent of LD ranges from moderate to strong. Only when LD is very weak or absent is the DMLB slightly less powerful than the mean test; in such cases, the TDT has essentially no power to detect linkage. Therefore, the DMLB test is an interesting approach to linkage detection when the extent of LD is unknown.
The C5 Convertase Is Not Required for Activation of the Terminal Complement Pathway in Murine Experimental Cerebral Malaria

Cerebral malaria (CM) is the most severe manifestation of clinical malaria syndromes and has a high fatality rate especially in the developing world. Recent studies demonstrated that C5−/− mice are resistant to experimental CM (ECM) and that protection was due to the inability to form the membrane attack complex. Unexpectedly, we observed that C4−/− and factor B−/− mice were fully susceptible to disease, indicating that activation of the classical or alternative pathways is not required for ECM. C3−/− mice were also susceptible to ECM, indicating that the canonical C5 convertases are not required for ECM development and progression. Abrogation of ECM by treatment with anti-C9 antibody and detection of C5a in serum of C3−/− mice confirmed that C5 activation occurs in ECM independent of C5 convertases. Our data indicate that activation of C5 in ECM likely occurs via coagulation enzymes of the extrinsic protease pathway. Background: The terminal complement pathway contributes to cerebral malaria (CM) pathogenesis. Results: The terminal pathway is activated in CM through a unique mechanism independent of the C5 convertases. Conclusion: We propose that enzymes of the coagulation system activate C5 in CM. Significance: Inhibition of complement at the level of C5 represents a unique therapeutic target in CM.
Mutations in the measles virus C protein that up regulate viral RNA synthesis.

Abstract The measles virus RNA-dependent RNA polymerase consists of two virus-encoded subunits, the phosphoprotein (P) and the large (L) protein. The P mRNA also codes for a C protein in the +1 reading frame relative to P. The activities of the measles P and C proteins from the vaccine strain, EdB, a wild-type CM strain, and an SSPE P4 strain were investigated using a CAT reporter minigenome assay. CAT is synthesized following replication and transcription of a DI-CAT minigenome supported by individual P, L, and N plasmids expressed in a mammalian expression system. As measured by CAT activity, CMP1 and P4P1 stimulate transcription and replication four- to six- and six- to eightfold, respectively, better than EdP. There are 10 and 16 amino acid changes in the P protein and three and four changes in C in CMP1 and P4P1, respectively, relative to EdP. By constructing chimeric P genes we showed that mutations throughout P4P1 were required for enhanced polymerase activity, while only mutations in the 5′-terminal portion, encompassing the C ORF, of the CMP1 gene mediated stimulation. Abrogation of C expression from the Ed and CM P genes resulted in an increase in RNA synthesis of twofold for CMP1S and four- to fivefold for EdPS. With the addition of C protein expressed from a separate plasmid that contains only the C ORF, EdC reduces viral RNA synthesis more strongly than CMC. These data suggest that EdC and CMC proteins give a differential inhibition that accounts for most of the differences in RNA synthesis by EdP and CMP1.
Beta 1 isoform-specific regulation of a triiodothyronine-induced gene during cerebellar development.

Although tissue-specific expression of the alpha 1 and beta 1 thyroid hormone receptors (TR-alpha 1 and TR-beta 1) suggests isoform-specific function, transfection studies to date have failed to show consistent differences in their ability to regulate gene expression. We here provide evidence that TR-beta 1 but not TR-alpha 1 regulates the expression of the gene coding for PCP-2 in cerebellar Purkinje cells during neonatal rat development and that such regulation appears to be both T3 dependent and T3 independent. Examination of neonatal rats revealed that the levels of three mRNAs expressed in cerebellar Purkinje cells (myoinositol-1,4,5-triphosphate receptor, calbindin, and PCP-2) rise from neonatal day 1 to day 15. This rise is preceded by the previously documented surge in brain T3 and TR-beta 1. Methimazole-induced hypothyroidism sharply reduces, but does not abolish, the rise in these mRNAs. Concomitant T3 administration normalizes the process. In order to establish more directly the role of TR-beta...
The SIRTF Science Operations System

The Space Infrared Telescope Facility (SIRTF) will be launched in early 2003, and will perform an extended series of science observations at wavelengths ranging from 3.6 to 160 microns for five years or more. The California Institute of Technology has been selected as the home for the SIRTF Science Center (SSC). The SSC is completing the final stages of prelaunch development and testing of the Science Operations System (SOS), which will support science operations of the Observatory. The SOS supports a variety of functions including observing proposal submission by the scientific community, long range planning and short term scheduling of the Observatory, instrument performance monitoring during nominal operations, and production of a variety of scientific archival products. This paper describes the role and function of the SSC, the architecture of the SOS, and discusses the major SOS subsystems. Examples of products generated by the SOS are included
Nonpeptide angiotensin II receptor antagonists: in vivo inhibition of [125I-Sar1,Ile8]angiotensin II binding by losartan, EXP597 and L-159,282 in rats.

Effects of losartan, L-159,282 and EXP597 on the in vivo binding of [125I-Sar1, Ile8]angiotensin II to kidney cortex and adrenal were examined in rats. Losartan, an AT1 receptor antagonist, completely blocked [125I-Sar1, Ile8]angiotensin II binding to the kidney cortex which contains only AT1 binding sites with an ID50 of 0.06 mg/kg. Losartan partially inhibited [125I-Sar1, Ile8]angiotensin II binding to the adrenal which contains equal amounts of AT1 and AT2 binding sites. Blockade by the AT1 receptor antagonist L-159,282 sufficiently increased the plasma levels of angiotensin II to block the AT2 receptor. EXP597 inhibited [125I-Sar1, Ile8]angiotensin II binding to the kidney cortex and adrenal almost totally with ID50S of 0.05 and 0.06 mg/kg, respectively. This result suggests that EXP597 exhibits almost equal binding affinity for AT1 and AT2 binding sites in vivo in rats.
Lymphocyte calcium signaling from membrane to nucleus

Ca(2+) signals control a variety of lymphocyte responses, ranging from short-term cytoskeletal modifications to long-term changes in gene expression. The identification of molecules and channels that modulate Ca(2+) entry into T and B lymphocytes has both provided details of the molecular events leading to immune responses and raised controversy. Here we review studies of the pathways that allow Ca(2+) entry, the function of Ca(2+) in the regulation of cell polarity and motility and the principles by which Ca(2+)-dependent transcription regulates lymphocyte function.