cssi/SciSciGPT-SciSciNet huggingface dataset:
Hospital-Based Active Shooter Incidents: Sanctuary Under Fire

This article addresses the prevalence of hospital-based active shooter incidents and explores how the legal system, hospitals, and hospital employees have approached and responded to associated safety and health concerns. Especially in light of recent Supreme Court decisions that have interpreted the Second Amendment expansively, fundamental challenges arise specifically from the wide availability of firearms in the United States in conjunction with often-inconsistent access to mental health services. While these underlying problems demand increased attention, this article proposes opportunities to mitigate risks at all levels.
Endothelin receptor antagonism improves glucose handling, dyslipidemia, and adipose tissue inflammation in obese mice

Endothelin-1 (ET-1) is elevated in patients with obesity; however, its contribution to the pathophysiology related to obesity is not fully understood. We hypothesized that high ET-1 levels cause dyslipidemia, inflammation, and insulin resistance within the adipose tissue of obese mice. To test this hypothesis, male C57BL/6J mice were fed either normal diet (NMD) or high-fat diet (HFD) for 8 weeks followed by 2 weeks of treatment with either vehicle, atrasentan (ETA receptor antagonist, 10 mg/kg/day) or bosentan (ETA/ETB receptor antagonist, 100 mg/kg/day). Atrasentan and bosentan lowered circulating non-esterified free fatty acids and triglycerides seen in HFD mice, while atrasentan-treated mice had significantly lower liver triglycerides compared with non-treated HFD mice. ET-1 receptor blockade significantly improved insulin tolerance compared with insulin-resistant HFD mice and lowered expression of genes in epididymal white adipose tissue (eWAT) associated with insulin resistance and inflammation. Flow cytometric analyses of eWAT indicated that HFD mice had significantly higher percentages of both CD4+ and CD8+ T cells compared with NMD mice, which was attenuated by treatment with atrasentan or bosentan. Atrasentan treatment also abolished the decrease in eosinophils seen in HFD mice. Taken together, these data indicate that ETA and ETA/ETB receptor blockade improves peripheral glucose homeostasis, dyslipidemia and liver triglycerides, and also attenuates the pro-inflammatory immune profile in eWAT of mice fed HFD. These data suggest a potential use for ETA and ETA/ETB receptor blockers in the treatment of obesity-associated dyslipidemia and insulin resistance.
Visual explanations from spiking neural networks using inter-spike intervals.

By emulating biological features in brain, Spiking Neural Networks (SNNs) offer an energy-efficient alternative to conventional deep learning. To make SNNs ubiquitous, a ‘visual explanation’ technique for analysing and explaining the internal spike behavior of such temporal deep SNNs is crucial. Explaining SNNs visually will make the network more transparent giving the end-user a tool to understand how SNNs make temporal predictions and why they make a certain decision. In this paper, we propose a bio-plausible visual explanation tool for SNNs, called Spike Activation Map (SAM). SAM yields a heatmap (i.e., localization map) corresponding to each time-step of input data by highlighting neurons with short inter-spike interval activity. Interestingly, without the use of gradients and ground truth, SAM produces a temporal localization map highlighting the region of interest in an image attributed to an SNN’s prediction at each time-step. Overall, SAM outsets the beginning of a new research area ‘explainable neuromorphic computing’ that will ultimately allow end-users to establish appropriate trust in predictions from SNNs.
Medical and Social Determinants of Brain Health and Dementia in a Multicultural Community Cohort of Older Adults

Background Socioeconomic status (SES), race, ethnicity, and medical comorbidities may contribute to Alzheimer's disease and related disorders (ADRD) health disparities. Objective Analyze effects of social and medical determinants on cognition in 374 multicultural older adults participating in a community-based dementia screening program. Methods We used the Montreal Cognitive Assessment (MoCA) and AD8 as measures of cognition, and a 3-way race/ethnicity variable (White, African American, Hispanic) and SES (Hollingshead index) as predictors. Potential contributors to health disparities included: age, sex, education, total medical comorbidities, health self-ratings, and depression. We applied K-means cluster analyses to study medical and social dimension effects on cognitive outcomes. Results African Americans and Hispanics had lower SES status and cognitive performance compared with similarly aged Whites. We defined three clusters based on age and SES. Cluster #1 and #3 differed by SES but not age, while cluster #2 was younger with midlevel. Cluster #1 experienced the worse health outcomes while cluster #3 had the best health outcomes. Within each cluster, White participants had higher SES and better health outcomes, African Americans had the worst physical performance, and Hispanics had the most depressive symptoms. In cross-cluster comparisons, higher SES led to better health outcomes for all participants. Conclusion SES may contribute to disparities in access to healthcare services, while race and ethnicity may contribute to disparities in the quality and extent of services received. Our study highlights the need to critically address potential interactions between race, ethnicity, and SES which may better explain disparities in ADRD health outcomes.
Orbital cellulitis and cavernous sinus thrombosis with contralateral sinus disease in a COVID-19 positive adolescent patient

Patients with COVID-19 have been reported to have elevated coagulation factors, which is a well-documented cause of venous thromboembolism events such as deep vein thrombosis and pulmonary embolism. Other venous thrombotic events, however, such as cavernous sinus thrombosis (CST) have been less commonly observed, specifically in combination with primary orbital cellulitis. Due to its unique anatomic location, the cavernous sinus is susceptible to thrombophlebitis processes including septic thrombosis and thrombosis most commonly from sinusitis. Many studies have shown that in the antibiotic era thromboembolic events of the cavernous sinus are less common due to infection spread from the orbit or facial region. This case report describes a 17-year-old COVID-19 positive male who presented with a left-sided primary orbital cellulitis with CST without radiographic evidence of ipsilateral sinus disease.
The Central Role of Heuristic Search in Cognitive Computation Systems

This paper focuses on the relation of heuristic search and level of intelligence in cognitive computation systems. The paper begins with a review of the fundamental properties of a cognitive computation system, which is defined generally as a control system that generates goal-directed actions in response to environmental inputs and constraints. An important property of cognitive computations is the need to process local cues in symbol structures to access and integrate distal knowledge to generate a response. To deal with uncertainties involved in this local-to-distal processing, the system needs to perform heuristic search to locate and integrate the right set of distal structures. The level of intelligence of the system depends critically on the efficiency of the heuristic search process. It is argued that, for a bounded rationality system, the level of intelligence does not depend on how much search it needs to do to accomplish a task. Rather, the level of intelligence depends on how much search it does not need to do to achieve the same level of performance. Examples were discussed to illustrate this idea. The first two examples show how machines that play games like tic-tac-toe and chess rely heavily on the efficiency of the heuristic search algorithm to achieve better performance, demonstrating the relation of heuristic search and intelligence in a bounded rationality system. The second example shows how humans adapt to different information ecologies to perform information search on the Internet and how their performance improves over time, demonstrating how heuristic search can be improved in an adaptive rationality system. The two examples demonstrate how better search control knowledge and representations of task environment can improve the efficiency of heuristic search, thereby improving the intelligence of the system.
Computations of Compressible Reactive Flows

This papers describes the results of a series of computations that show the general approach developed in the Laboratory for Computational Physics and Fluid Dynamics for solving complex combustion problems. The basis of the approach is to use use specially designed numerical models implemented on high-speed, vector and parallel-processing computers as tools for investigating the details of the behavior of complex physical systems. We have applied this approach to problems in detonations, flames, turbulence, and transition processes.
Assimilation of Observations with Models to Better Understand Severe Ionospheric Weather at Mid-Latitudes

For many decades, the mid-latitude ionosphere was regarded as well characterized even if not well modeled. As a result, the Federal Aviation Authority's Wide Area Augmentation System (WAAS) was developed to provide augmented GPS positioning information to correct for ionospheric variability. However, over the past 5 years, recurrent superstorms in the ionosphere have forced the WAAS system to go offline for many hours at a time. This report discusses present-day knowledge regarding these conditions and how they are associated with unexpectedly steep horizontal gradients in the mid-latitude ionosphere total electron content (TEC). In a general sense, the possible physical mechanisms are understood, but during a storm the distribution and evolution of the driving forces for these mechanisms are neither understood nor adequately observed, the two main driving forces being the convection electric field and the neutral wind. In this paper a simplified convection electric field pattern is presented and used to drive a physics-based ionospheric model. This demonstrates how the superstorm ionospheric condition could be generated. Data assimilation is a new approach that could exceed present-day empirical and physical model limitations. There are three main expectations for data assimilation: (1) combined with a good ionospheric background model, the data assimilation must provide realistic global specification of the ionosphere; (2) it must also provide additional information about the ionosphere that is not already evident in the observation, that is, altitude profiles of the electron density when only slant TEC integrals of the electron density are available; and (3) with full physics-based models in the assimilation procedure, data assimilation models must also provide the drivers, that is, the neutral wind and electric field patterns. This paper examines the current status of these three expectations with regard to the future for the scientist and the space weather forecaster.
The value of the endometrial biopsy: A study of 14,655 office endometrial biopsies☆

Abstract Endometrial biopsy used routinely as a screening method for the detection of endometrial carcinoma resulted in the discovery of 102 cases. Twenty-one per cent of these were asymptomatic and unsuspected. Of the 102 cases treated, only 28 had positive or atypical Papanicolaou smears. Additional contributions to the care of the gynecologic patient were significant as a result of specific findings by 14,655 endometrial biopsies performed.
The incest taboo: Loosened sexual boundaries in remarried families

Abstract Household sexual abuse is reported here as a dysfunction in some remarried families with a child who presents problems of depression, suicidal gestures, adolescent rebelliousness, or poor school achievement. Common dynamics of the family and each family member are explored and treatment issues are discussed. A child's ability to admit abuse is a function of the therapist's comfort in hearing it, ability to deal with anger, and need to exercise control. Various forms of sexual abuses and their treatment are illustrated with case histories.
The relation between the deflocculating and frothing powers of soaps

In order to determine directly the relation between frothing and deflocculation the essential features of the “graphite test” and other frothing tests were combined with the “carbon black test,” and a possible modification of the latter was suggested. It appears that frothing and deflocculation are concomitant, not sequent, phenomena, and that both are due to a similar mechanism. But the parallelism between the two appears so poor that no test for frothing power, whether utilizing the froth in a qualitative or quantitative way, deserves much confidence as an indication of probable deflocculating power.
Detector car history and new developments

THE rail detector car is an assemblage of specialized test equipment mounted on self-propelled railroad cars and is used for the detection of all types of defects that develop in railroad rails. The story of detector cars should start a few years before there were any such cars. Before 1926, the railroads were faced with a serious and fast-growing menace to their very life: the breaking of rails. The source of this menace was the transverse fissure, a very thin crack which would start within the rail and develop outwardly until it caused the rail to break.
DIRECT CALCIUM-STIMULATED RELEASE OF GLUCAGON FROM THE ISOLATED PERFUSED RAT PANCREAS AND THE EFFECT OF CHEMICAL SYMPATHECTOMY

"Staircase" increments of calcium (from 0.5 to 15 mEq/L) were added to the perfused rat pancreas in the absence of glucagon secretogogues. Large spikes of glucagon release resulted, particularly at the small and large calcium concentrations. Insulin secretion was undetectable. Selective destruction of peripheral adrenergic neurons by pretreatment of the rats with 6-hydroxydopamine reduced the basal glucagon secretion to about 50% and specifically suppressed the calcium-induced glucagon release at the lower calcium steps. The response to a subsequent stimulation by arginine/calcium was not inhibited. Results suggest that glucagon secretion is modulated by a stimulant effect of the pancreatic adrenergic nerves (norepinephrine?) and that calcium in part positively affects release by permitting this neural stimulation.
Biofilms of chitosan-gold nanorods as a novel composite for the laser welding of biological tissue

Gold nanorods (GNRs) exhibit intense localized plasmon resonances at optical frequencies in the near infrared (NIR), which is the window where the penetration of light into the body is maximal. Upon excitation with a NIR laser, a strong photothermal effect is produced, which can be exploited to develop minimally invasive therapies. Here we prove the use of chitosan-GNRs films as a novel NIR sensitive nanocomposite for the photothermal conversion of NIR laser light during surgical interventions of tissue welding. Chitosan is an attractive biomaterial due to its biodegradability, biocompatibility, hemostatic, antimicrobial and wound healing-promoting activity. Colloidal GNRs were embedded in chitosan based, highly stabilized, flexible and easy-to-handle films, which were stored in water until the time of surgery. The chitosan-GNRs films were first positioned on freshly explanted rabbit tendon samples. Then, by administration of single pulses ranging from 80 to 140 ms duration and 0.5 to 1.5 W power delivered by a 300-μm optic fiber coupled with a 810 nm diode laser, spots of local thermally-induced adhesion characterized by a tensile strength of ~ 10 kPa were obtained. The present results are encouraging toward the development of a novel minimally-invasive technology based on the application of bioderived nanoplasmonic materials to biomedical optics.
Picosecond spectroscopy applied to the study of chemical and biological reactions

The techniques employed by picosecond spectroscopy are reviewed. These include the generation of fixed and tuneable picosecond radiation as well as time-resolved absorption and fluorescence measurements. In addition to mode-locked lasers, other methods of making subnanosecond measurements such as phase fluorometry, beat noise detection from a cw laser, and coherent excitation are covered. Picosecond spectroscopy is now applied to a variety of chemical and biological problems. Vibrational relaxation due to both dephasing and energy transfer is one of the most active areas of this field and yields a great quantity of information on the influence of molecular structure on this phenomena. Both electron transfer and proton transfer in the excited state have been studied by a number of workers. Singlet and triplet state photochemistry are now being probed with picosecond resolution. Energy transfer and radiationless transitions were among the first phenomena probed by picosecond lasers. Recent advances in detectors, such as the streak camera, have opened new avenues of exciting research in this area. Finally, the application of picosecond spectroscopy to biological systems has created a great deal of impact. Work by several groups on photosynthetic organisms has revolutionized our understanding of energy transduction. Similar progress has been made inmore » unraveling some of the early steps in the visual process. 276 references; 28 figures; 4 tables.« less
Retinofugal projections to the hypothalamus, anterior thalamus and basal forebrain in hamsters

In Part a of the study, the retinal inputs to the hypothalamus, anterior thalamus and basal forebrain of Syrian hamsters were studied using intraocular injections of horseradish peroxidase conjugated to cholera toxin (CT-HRP). In the hypothalamus, the heaviest retinal input was to the suprachiasmatic nucleus (SCN), however, many labeled fibers coursed through the SCN to reach more caudal, periventricular and lateral sites including the anterior and lateral hypothalamus, the paraventricular nucleus (PVN), the subparaventricular zone, the ventromedial nucleus and the pars compacta of the dorsomedial nucleus. Some of these fibers continued dorsally into the zona incerta (ZI). Other fibers emerged from the lateral optic chiasm and traveled either rostro-medially to end in the preoptic area (POA) or further laterally to reach the supraoptic nucleus. A subset of fibers extended laterally from the chiasm to form a well-defined tract which provided input to the pyriform cortex. The extrageniculate retinal input to the thalamus was to the anterior thalamic area (AT) via the stria terminalis. In Part b, injections of rhodamine-labeled latex microspheres were made in three brain areas that contained labeled fibers after intraocular injections of CT-HRP. Injections in the AT, PVN/ZI area and POA consistently produced a small number of labeled retinal ganglion cells, whereas control injections did not. Taken together, these results indicate that many regions of the brain involved in the control of reproductive and regulatory functions receive photic informations via direct retinal inputs. These retinal inputs may play a role in the photoperiodic modulation of physiology and behavior.
Geographies of global Internet censorship

More than one-quarter of the planet’s population uses the Internet today, although access to it is highly uneven throughout the world. While it is widely celebrated for its emancipatory potential, many governments view the Internet with alarm and have attempted to limit access or to control its contents. This project seeks to provide a comprehensive, theoretically informed analysis of the geographies of Internet censorship. It begins by clarifying the reasons, types, extent of, and opposition to, government limitations of Internet access and contents. Invoking an index of censorship by Reporters Without Borders, it maps the severity of censorship worldwide and assesses the numbers of people affected, and using the Freedom House index, it correlates political liberty with penetration rates. Second, it explores Internet censorship at several levels of severity to explicate the multiple means through which censorship is implemented and resisted. The third part offers a moral critique of Internet censorship via a Habermasian interpretation of cyberspace as the closest real-world approximation of an ideal speech situation. The summary notes the paradox of growing e-government and continued fears of an expanded domain of public discourse.
Substitution of tetramethylbenzidine for benzidine in cyanide analyses

Benzidine (B, p-diaminodiphenyl) has been used in analytical laboratories for many years in assays for plasma hemoglobin [l], inorganic cyanide, and thiocyanate ]2,3]. The chemistry involved in the two assays for the inorganic anions is the same, but quite different from the hemoglobin assay. In the classical assay for plasma hemoglobin, the hemoglobin functions as a pseudoperoxidase and B, in the presence of hydrogen peroxide, is converted to a quinoid chromophore, B blue, and eventually to other quinoid forms [I]. In the assay for cyanide and thiocyanate, both are converted to cyanogen bromide by excess elemental bromine. Arsenous acid is used to destroy the excess bromine. Cyanogen bromide is then reacted with pyridine to generate glutaconic aldehyde which in turn reacts with B to form a Schiff base chromophore [4]. Because B is an established carcinogen, there is increasing reluctance to permit its use for these analytical applications and severe restrictions have been placed on its production [S]. A non-carcinogenic derivative of B, 3,3’,5,5’-tetramethylben~dine (TMB), has been successfully substituted in the plasma hemoglobin assay without loss of sensitivity, precision, or accuracy [6]. Here we show that the same is true for the assay of cyanide and thiocyanate. This new technique has been applied to measurements of cyanide released in vitro from sodium nitroprusside (SNP) during incubations with human red blood cells, platelets, and plasma.
Theoretical and experimental analysis of tethered buoy instability in gravity waves

Abstract The motion of a tethered spherical buoy subjected to incident regular waves was measured in a wave tank. Transverse instability was observed when the period of the wave generated was close to one-half of the natural period of the buoy. The transverse instability confirmed as Mathieu type was predominant at the surface but diminished with increase in the depth of submergence. The stable and unstable zones were determined on the Mathieu's instability diagram. Experimental results were in agreement with the predicted zone of instability for a two degree of freedom oscillation problem of Mathieu type which has a periodically varying spring constant.
Absolute Measurements of Electron Excitation Cross Sections in C3

Spectral emissions from C3+ are of importance in solar, planetary and astrophysical plasmas. In these plasmas the population of excited states is often dominated by electron impact excitation. Accurate cross sections for this process are required to determine parameters such as electron and ion densities. The 2s 2S–2p 2P transition in C3+ is of particular interest as it allows direct comparisons among the results of several different experimental and theoretical groups. Employing the electron energy-loss technique we have measured cross sections to several eV above threshold, a region where there is still significant disagreement among previous results.
A STRATEGY FOR THE IDENTIFICATION OF PROTEINS LOCALIZED TO SUBCELLULAR SPACES : APPLICATION TO E. COLI PERIPLASMIC PROTEINS

A strategy for the identification of proteins localized to subcellular spaces is illustrated. Proteins in the periplasmic space of E. coli were enriched by the procedure of Neu and Hoppel, and the complicated protein mixture was partially fractionated by using strong anion exchange chromatography [1]. An aliquot from each fraction was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with high sensivity silver staining for protein detection. An additional aliquot of the mixture was digested with the enzyme trypsin and then analyzed by using microcolumn liquid chromatography electrospray ionization tandem mass spectrometry (LC/MS/MS), employing an instrument control program to automatically acquire tandem mass spectra. The tandem mass spectra were then used to search the E. coli sequence database. Approximately 159 bands appeared on the gels for the enriched proteins. A total of 80 proteins were identified by LC/MS/MS from the chromatographic fractions.
The Fermi-Pasta-Ulam problem: Paradox turns discovery

Abstract This pedagogical review is written as a personal retrospective which seeks to place the celebrated Fermi, Pasta, and Ulam paradox into historical perspective. After stating the Fermi-Pasta-Ulam results, we treat the questions it raises as a pedagogical “skeleton” upon which to drape (and motivate) the evolving story of nonlinear dynamics/chaos. This review is thus but another retelling of that story by one intimately involved in its unfolding. This is done without apology for two reasons. First, if my colleagues have taught me anything, it is that an audience of experts will seldom pay greater attention than when, with some modicum of grace and polish, they are told things they know perfectly well already. Second, if generations of students have taught me anything, it is that few things fascinate them more than a scientific mystery — and the Fermi-Pasta-Ulam paradox is a cracker-jack mystery. And so readers, especially graduate students curious about nonlinear dynamics/chaos, are now invited to sit back, loosen their belts (and minds), and prepare for fact that sometimes reads like fantasy.
Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows.

Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows. Adult males received dietary exposures of BDE-209 at a low dose (∼3 ng/g bw-day) and high dose (∼300 ng/g bw-day) for 28 days followed by a 14-day depuration to evaluate recovery. Compared to controls, fish exposed to the low dose for 28 days experienced a 53% and 46% decline in circulating total thyroxine (TT4) and 3,5,3′-triiodothyronine (TT3), respectively, while TT4 and TT3 deficits at the high dose were 59% and 62%. Brain deiodinase activity (T4-ORD) was reduced by ∼65% at both doses. BDE-209 elevated the relative mRNA expression of genes encoding deiodinases, nuclear thyroid receptors, and membrane transporters in t...
UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids

Attachment of the small protein ubiquitin (Ub) to substrates is a reversible covalent modification that regulates the stability, activity and localization of target proteins. Assembly of ubiquitin chains requires three enzyme activities: a Ub-activating (E1) enzyme, a Ub-conjugating (E2) enzyme and a Ub ligase (E3). E2 enzymes are responsible both for E3 selection and substrate modification and for much of the diversity of Ub cellular signalling. The E2 UbcH7 shows broad specificity for HECT-type E3, but often fails to function with RING E3s despite its ability to form specific complexes. Rachel Klevit and colleagues demonstrate that UbcH7 exhibits robust activity with a family of E3 ligases that are RING/HECT hybrids: they bind to E2s through a RING domain but transfer Ub through a HECT-like mechanism. They propose that the intrinsic chemical reactivity of an E2 is a powerful predictor in determining with which class of E3 it will function. Although the functional interaction between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s) is essential in ubiquitin (Ub) signalling, the criteria that define an active E2–E3 pair are not well established. The human E2 UBCH7 (also known as UBE2L3) shows broad specificity for HECT-type E3s1, but often fails to function with RING E3s in vitro despite forming specific complexes2,3,4. Structural comparisons of inactive UBCH7–RING complexes with active UBCH5–RING complexes reveal no defining differences3,4, highlighting a gap in our understanding of Ub transfer. Here we show that, unlike many E2s that transfer Ub with RINGs, UBCH7 lacks intrinsic, E3-independent reactivity with lysine, explaining its preference for HECTs. Despite lacking lysine reactivity, UBCH7 exhibits activity with the RING-in-between-RING (RBR) family of E3s that includes parkin (also known as PARK2) and human homologue of ariadne (HHARI; also known as ARIH1)5,6. Found in all eukaryotes7, RBRs regulate processes such as translation8 and immune signalling9. RBRs contain a canonical C3HC4-type RING, followed by two conserved Cys/His-rich Zn2+-binding domains, in-between-RING (IBR) and RING2 domains, which together define this E3 family7. We show that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer Ub through an obligate thioester-linked Ub (denoted ∼Ub), requiring a conserved cysteine residue in RING2. Our results define the functional cadre of E3s for UBCH7, an E2 involved in cell proliferation10 and immune function11, and indicate a novel mechanism for an entire class of E3s.
6th Dysferlin Conference, 3–6 April 2013, Arlington, Virginia, USA

Abstract The 2013 Dysferlin Conference, sponsored and organized by the Jain Foundation, was held from April 3–6, 2013 in Arlington, VA. Participants included 34 researcher speakers, 5 dysferlinopathy patients and all 8 members of the Jain Foundation team. Dysferlinopathy is a rare disease that typically robs patients of mobility during their second or third decade of life. The goals of these Dysferlin Conferences are to bring experts in the field together so that they will collaborate with one another, to quicken the pace of understanding the biology of the disease and to build effective platforms to ameliorate disease. This is important because the function of dysferlin and how to compensate for its absence is still not well understood, in spite of the fact that the dysferlin gene was identified more than a decade ago. The objective of this conference, therefore, was to share and discuss the newest unpublished research defining the role of dysferlin in skeletal muscle, why its absence causes muscular dystrophy and possible therapies for dysferlin-deficient muscular dystrophy patients.
A ferroan region of the lunar highlands as recorded in meteorites MAC88104 and MAC88105

MAC88104 and 88105, paired meteorites of noritic anorthosite composition, are examined. Results indicate that these meteorites contain a variety of materials including impact-melt breccias, igneous and metamorphosed bressia clasts, glass clasts and veins, mineral clasts, and extralunar meteoritic debris. Compositions of the bulk meteorite and its components suggest that it came from a region of the moon's crust that was highly aluminous, low in incompatible trace elements, and ferroan in character.
Contribution of the crystalline lens to the spherical aberration of the eye

The influence of the corneal shape on the quality of the retinal image has been studied. We have distinguished between the role of the cornea and that of the crystalline lens; the wave surface behind the cornea was determined. First, the corneal topology was measured by photographic keratometry. Then, for the same subject, the spherical aberration of the eye was determined by the Foucault knife-edge test. The shapes of the anterior and posterior surfaces of the crystalline lens have been determined from experimental data.
Contralateral femoral vein removal of a circumferentially ruptured balloon-catheter following pulmonary artery angioplasty.

While attempting to remove a circumferentially ruptured balloon following branch pulmonary artery angioplasty, the shaft of the catheter broke, leaving the distal portion of the balloon and catheter in the femoral vein but still on the exchange wire. We describe a method to retrieve the broken balloon catheter via the contralateral femoral vein.© 1993 Wlley-Liss, Inc
Dynamics of GPIIb/IIIa-mediated platelet-platelet interactions in platelet adhesion/thrombus formation on collagen in vitro as revealed by videomicroscopy

The conventional description of platelet interactions with collagen-coated surfaces in vitro, based on serial static measurements, is that platelets first adhere and spread to form a monolayer and then recruit additional layers of platelets. To obtain dynamic information, we studied gravity-driven platelet deposition in vitro on purified type 1 collagen by video phase-contrast microscopy at 22°C. With untreated human and wild-type mouse platelets, soon after the initial adhesion of a small number of “vanguard” platelets, “follower” platelets attached to the spread-out vanguard platelets. Follower platelets then adhered to and spread onto nearby collagen or over the vanguard platelets. Thus, thrombi formed as a concerted process rather than as sequential processes. Treatment of human platelets with monoclonal antibody (mAb) 7E3 (anti–GPIIb/IIIa (αIIbβ3) + αVβ3) or tirofiban (anti–GPIIb/IIIa) did not prevent platelet adhesion but nearly eliminated the deposition of follower platelets onto vanguard platelets and platelet thrombi. Similar results were obtained with Glanzmann thrombasthenia platelets. Wild-type mouse platelets in the presence of mAb 1B5 (anti–GPIIb/IIIa) and platelets from β3-null mice behaved like human platelets in the presence of 7E3 or tirofiban. Deposition patterns of untreated human and wild-type mouse platelets were consistent with random distributions under a Poisson model, but those obtained with 7E3- and tirofiban-treated human platelets, 1B5-treated mouse platelets, or β3-null platelets demonstrated a more uniform deposition than predicted. Thus, in this model system, absence or blockade of GPIIb/IIIa receptors interferes with thrombus formation and alters the pattern of platelet deposition.
Purification and properties of reconstitutively active and inactive adenosinetriphosphatase from Escherichia coli.

Abstract The Mg2+- and Ca2+-stimulated ATPase (EC 3.6.1.3; ATP phosphohydrolase) (bacterial coupling factor) was purified from two strains of E. coli by two different procedures: (a) method of Nelson, Kanner, and Gutnick [Proc. Nat. Acad. Sci. USA (1974) 71, 2720-2724] and (b) a modified procedure described in this paper. The ATPase purified from E. coli K12 (λ) by the first procedure had 4 subunits (α, β, γ, and e). It did not bind to a deficient membrane, nor did it reconstitute ATP-driven transhydrogenase activity. Our modified procedure (b) yielded 5 subunits (α, β, γ, δ, and e). This ATPase could bind to a deficient membrane and reconstitute ATP-driven transhydrogenase. This finding suggests that the δ subunit is required for the reaction with the membrane. The molecular weight of the 4-subunit ATPase was significantly lower than that of the 5-subunit ATPase, as judged by equilibrium centrifugation. The specific ATPase activities of both preparations were about the same. These two procedures were also applied to E. coli ML308-225.
Imitation in Large Complex Organizations: A Case of Design for Six Sigma in the Automobile Industry

As companies seek to become lean enterprises, they can take several alternative paths. One extreme is to mechanistically copy tools that work in another company's context to give the appearance of “doing lean” (mechanistic); another is to work to learn and adapt the principles to the local environment developing a culture of organizational learning (organic). Companies that have had some degree of success with lean in manufacturing often decide to move upstream to the engineering design phase. One set of tools for doing this is Design for Six Sigma (DFSS). This article recounts a detailed case study in which executives managing a mechanistic organizational culture, General Motors, decided to copy DFSS, which was purported to be a key success factor in Hyundai's greatly improved product quality. By converting the problem into one of mechanically copying specific tools, General Motors failed to incorporate DFSS into a learning culture, and the process led to mechanistic individual learning of rote procedure...
Chlorinated maleinized guayule rubber as an adhesion promoter for polypropylene

Chlorinated maleinized guayule rubbers (CMGR) were synthesized and applied as coatings onto polypropylene panels. CMGR orientation was critical to adhesion and was verified by contact angle measurements. Reducing the quantity of tetrahydrofuran (THF) decreased adhesion from 57 N/cm2 with pure THF to 23 N/cm2 with four percent THF in water. Percent maleinization above a critical concentration of 15 by weight decreased adhesion. However, 10% maleinization was required for dispersion stability in water while 5–10% concentration provided maximum adhesion. A five percent maleic CMGR dispersion at 240 g/L THF concentration was stable for less than 24 hr while a 10% maleic anhydride concentration has shown long-term stability.
A numerical algorithm for optimal feedback gains in high dimensional linear quadratic regulator problems

A hybrid method for computing the feedback gains in linear quadratic regulator problems is proposed. The method, which combines use of a Chandrasekhar type system with an iteration of the Newton–Kleinman form with variable acceleration parameter Smith schemes, is formulated to efficiently compute directly the feedback gains rather than solutions of an associated Riccati equation. The hybrid method is particularly appropirate when used with large dimensional systems such as those arising in approximating infinite-dimensional (distributed parameter) control systems (e.g., those governed by delay-differential and partial differential equations). Computational advantages of the proposed algorithm over the standard eigenvector (Potter, Laub–Schur) based techniques are discussed, and numerical evidence of the efficacy of these ideas is presented.
Insights into the dynamics of HIV-1 protease: a kinetic network model constructed from atomistic simulations.

The conformational dynamics in the flaps of HIV-1 protease plays a crucial role in the mechanism of substrate binding. We develop a kinetic network model, constructed from detailed atomistic simulations, to determine the kinetic mechanisms of the conformational transitions in HIV-1 PR. To overcome the time scale limitation of conventional molecular dynamics (MD) simulations, our method combines replica exchange MD with transition path theory (TPT) to study the diversity and temperature dependence of the pathways connecting functionally important states of the protease. At low temperatures the large-scale flap opening is dominated by a small number of paths; at elevated temperatures the transition occurs through many structurally heterogeneous routes. The expanded conformation in the crystal structure 1TW7 is found to closely mimic a key intermediate in the flap-opening pathways at low temperature. We investigated the different transition mechanisms between the semi-open and closed forms. The calculated re...
Isolation and partial characterization of basolateral membranes from rat proximal colonic epithelial cells.

Abstract The isolation of basolateral membranes from rat proximal colonic epithelial cells is described. Cells were harvested using a technique combining chelation of divalent cations with mechanical dissociation. After homogenization, differential centrifugation yielded a ‘crude’ membrane fraction which was further purified using sucrose density centrifugation. The final membrane fraction was enriched 10–14-fold over homogenate in ouabain-sensitive sodium-potassium dependent adenosine triphosphatase and ouabain-sensitive potassium-dependent phosphatase specific activities. SDS-polyacrylamide gel electrophoresis of this membrane revealed at least 18 protein bands with molecular weights of 14 600–200 000. Phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, free cholesterol and fatty acids were the major lipid components of this membrane. The predominant fatty acids were palmitic (16:0), oleic (18:1), stearic (18:0) and linoleic (18:2) acid. Membranes and their liposomes were studied, using the lipid soluble fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH), by steady-state fluorescence polarization. The fluorescence anisotropy was greater in the intact membranes compared to their liposomes, indicating greater fluidity in the liposomes. Compositional studies suggested that the high fluidity of this membrane was due to its low ratios of protein/lipid (w/w), cholesterol/phospholipid (mol/mol), and sphingomyelin/phosphatidylcholine (mol/mol).
How can stores sustain their businesses? From shopping behaviors and motivations to environment preferences.

The purpose of this study was to (1) discover consumer purchasing behaviors while shopping as a tourist and shopping at home, and (2) investigate tourist shopping preferences for an ideal shopping environment. A sample of 1,235 respondents participated in this study. Survey participants were asked to evaluate what store attributes they desired and what sources of information they used while selecting a store to shop in during their trips. Results indicate that consumers utilized various shopping channels while shopping in various environments. Also, different types of consumers exhibited clear preferences toward their ideal shopping environment. The results of this study are helpful for future service providers, tourism businesses, and tourism retailers to plan product development, provide better services, and equip a wider range of service skills.
Orientational relaxation of water trapped inside C60 fullerenes

Abstract The synthesis of an endohedral C60 fullerene containing a single trapped H2O molecule was recently achieved [K. Kurotobi and Y. Murata, Science 333 (2011) 613–616]. In this Letter, a computational study is conducted to determine the dynamic properties of the trapped water for a range of temperatures between 50 and 300 K. MD and ab initio MD (AIMD) simulations show that, in the absence of hydrogen bonds, the orientational relaxation of H2O inside the fullerene cage is fast and nearly temperature independent. These properties could be exploited in the design of future nanotechnologies.
Leadership Definitions and Theorists: Do Practitioners and Professors Agree?

Leadership definitions are foundational to leadership theories. The survey assessed awareness and support level for definitions and theoretical positions among practitioners and professors. Eleven ...
A COLLABORATIVE NEGOTIATION TOOL

The system, implemented in Malone, Lei, et al's Object Lens (88; 89), is designed to support the negotiation that is part of any collaborative endeavor. Although it will not be discussed here (see Adelson, in The Social Creation of Knowledge. Ed: E. Barrett; MIT Press), the system is intended to be used with a collaborative authoring system which accommodates needs for privacy and supports project planning/scheduling. By accommodating users' needs for negotiation and privacy the two systems together offer the kind of psychological support that bolsters successful collaboration.
The octarepeat domain of the prion protein binds Cu(II) with three distinct coordination modes at pH 7.4.

The prion protein (PrP) binds Cu2+ in its N-terminal octarepeat domain. This unusual domain is comprised of four or more tandem repeats of the fundamental sequence PHGGGWGQ. Previous work from our laboratories demonstrates that at full copper occupancy, each HGGGW segment binds a single Cu2+. However, several recent studies suggest that low copper occupancy favors different coordination modes, possibly involving imidazoles from histidines in adjacent octapeptide segments. This is investigated here using a combination of X-band EPR, S-band EPR, and ESEEM, along with a library of modified peptides designed to favor different coordination interactions. At pH 7.4, three distinct coordination modes are identified. Each mode is fully characterized to reveal a series of copper-dependent octarepeat domain structures. Multiple His coordination is clearly identified at low copper stoichiometry. In addition, EPR detected copper−copper interactions at full occupancy suggest that the octarepeat domain partially collap...
It may take more than a shot: alternatives to immunotherapy for Alzheimer's disease.

In 1999, the field of Alzheimer's disease (AD) therapeutics was turned on its head by reports that active immunization against amyloid β (Aβ) could reduce accumulation of Aβ plaques in brains of transgenic mice engineered to model AD pathology. These studies were rapidly followed by preclinical studies from multiple laboratories demonstrating efficacy of passive immunization with Aβ specific antibodies and in some cases, amelioration of cognitive deficits seen in AD mouse models. Such findings launched intensive and continuing efforts to develop Aβ immunotherapy as a safe and effective treatment for AD. In this issue of Biological Psychiatry, Sarazin et al. (1) summarize the current status of immunotherapy for Alzheimer's disease. They highlight the challenging side effects observed in the original active Aβ immunization trial and provide a summary of the disappointing results achieved in recent phase III trials of passive Aβ immunotherapy. Concerns that these trials failed because intervention occurred too late in the disease course have spurred new trial designs targeting asymptomatic familial AD carriers. As the authors point out, all such studies are entirely predicated on the amyloid hypothesis. Notwithstanding the applicability of this hypothesis, and therefore therapy, to nonfamilial cases of AD, this review points out a number of challenges related to designing preventative immunotherapy trials for sporadic AD and the classification of at-risk subjects. Because of these challenges, from a cynical point of view, the most informative outcome of immunotherapy trials in familial AD would be failure.
Vaginal Bleeding and Abdominal Pain

A 12-yr-old white female presented to her private pediatrician with complaints of her stomach hurting “a lot” and irregular menses. The patient experienced menarche at 10 yrs 10 mos and had menses every 3 mos. Upon review of systems, the mother noted that the child was fatigued most of the time with little energy. No prior medical problems, hospitalizations, surgeries, or allergies were noted. Family history was noncontributory. The patient lived with mom, dad, and a 15-yr-old brother. Physical examination revealed a 12 8/12-yr-old white female with a height of 147 centimeters (15th percentile) and a weight of 49.5 kilograms (60th percentile). Her blood pressure was 98/60. General exam revealed full facies. Neurological exam revealed a questionable delay in relaxation phase of the patellar reflex. Head and neck exam was normal, with a normal thyroid palpable. Breast exam consistent with Tanner stage 1. Abdominal exam revealed a protuberant abdomen with no masses palpable. Pelvic exam showed pubic hair consistent with Tanner stage 4, normal labia majora and minora, and estrogenized full crescentic hymen. Internal exam was deferred.