cssi/SciSciGPT-SciSciNet huggingface dataset:
Association of metformin and statin medications with surrogate measures of cardiovascular disease in youth with type 1 diabetes: the SEARCH for diabetes in youth study

Purpose Youth with type 1 diabetes mellitus (T1DM) are at risk of cardiovascular disease (CVD). We evaluated if metformin or statin use was associated with surrogate measures of improved CVD. Methods We included participants from the SEARCH observational study. Participants treated with insulin plus metformin (n=42) or insulin plus statin (n=39) were matched with 84 and 78 participants, respectively, treated with insulin alone. Measures of arterial stiffness obtained were pulse wave velocity (PWV), augmentation index (AI75), and heart rate variability as standard deviation of the normal-to-normal interval (SDNN) and root mean square differences of successive NN intervals (RMSSD). Results CVD measures were not significantly different among participants on insulin plus metformin versus those on insulin alone: PWV (5.9±1.0 m/sec vs. 5.8±1.5 m/sec, P=0.730), AI75 (1.8 [-6.0 to 8.0] vs. -2.4 [-10.7 to 3.8], P=0.157), SDNN (52.4 [36.8-71.1] m/sec vs. 51.8 [40.1-74.9] m/sec, P=0.592), and RMSSD (43.2 [29.4-67.6] vs. 47.4 [28.0-76.3], P=0.952). CVD measures were not different for statin users versus nonusers: PWV (5.7±0.8 m/sec vs. 5.9 ±1.1 m/sec, P=0.184), AI75 ( -4.0 [-9.5 to 1.7] vs. -6.7 [-11.3 to 5.7], P=0.998), SDNN (54.6 [43.5-77.2] m/sec vs. 63.1 [44.2-86.6] m/sec, P=0.369), and RMSSD (49.5 [31.2-74.8] vs. 59.2 [38.3-86.3], P=0.430). Conclusion We found no associations of statin or metformin use with surrogate measures of CVD. Future prospective pediatric clinical trials could address this issue.
What Do Surveys of Program Completers Tell Us about Teacher Preparation Quality

Surveys of teacher preparation program (TPP) completers have become one widely used measure for program accountability and improvement, yet there is little evidence as to whether perceptions of pre...
Optimizing the monomer structure of polyhedral oligomeric silsesquioxane for ion transport in hybrid organic–inorganic block copolymers

Author(s): Gao, KW; Jiang, X; Hoffman, ZJ; Sethi, GK; Chakraborty, S; Villaluenga, I; Balsara, NP | Abstract: Poly(ethylene oxide)-b-polyhedral oligomeric silsesquioxane (PEO–POSS) mixed with lithium bis(trifluoromethanesulfonyl)imide salt is a nanostructured hybrid organic–inorganic block copolymer electrolyte that may enable lithium metal batteries. The synthesis and characteristics of three PEO–POSS block copolymer electrolytes which only differ by their POSS silica cage substituents (ethyl, isobutyl, and isooctyl) is reported. Changing the POSS monomer structure results in differences in both thermodynamics and ion transport. All three neat polymers exhibit lamellar morphologies. Adding salt results in the formation of a disordered window which closes and gives way to lamellae at higher salt concentrations. The width of disordered window decreases with increasing length of the POSS alkyl chain substituent from ethyl to isobutyl and is absent in the isooctyl sample. Rheological measurements demonstrate good mechanical rigidity when compared with similar all-organic block copolymers. While salt diffusion coefficient and current ratio are unaffected by substituent length, ionic conductivity increases as the length of the alkyl chain substituent decreases: the ethyl substituent is optimal for ion transport. This is surprising because conventional wisdom suggests that ion transport occurs primarily in the PEO-rich domains, that is, ion transport should be unaffected by substituent length after accounting for the minor change in conducting phase volume fraction. © 2020 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2020 © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 363–371.
The American Society of Retina Specialists Artificial Intelligence Task Force Report

Artificial intelligence (AI) is a growing area that relies on the heavy use of diagnostic imaging within the field of retina to offer exciting advancements in diagnostic capability to better unders...
Selective Area Epitaxy By Metalorganic Chemical Vapor Deposition– A Tool For Photonic And Novel Nanostructure Integration

Abstract Selective area epitaxial (SAE) growth of III-V materials and devices by metalorganic chemical vapor deposition is selectively reviewed to illustrate the concepts employed in this technology and its most relevant applications. Special focus on the use of SAE use for photonic integration, heterogeneous integration of materials relevant to photonic integration, and nanostructure integration is made. Throughout, the pioneering work led by Professor James J. Coleman is used to illustrate the value of using selective growth for various applications.
Aerosol generation with various approaches to oxygenation in healthy volunteers in the emergency department

Objectives: Health care workers experience an uncertain risk of aerosol exposure during patient oxygenation To improve our understanding of these risks, we sought to measure aerosol production during various approaches to oxygenation in healthy volunteers in an emergency department Methods: This was a prospective study conducted in an empty patient room in an academic ED The room was 10 ft long x 10 ft wide x 9 ft tall (total volume 900 ft3) with positive pressure airflow (1 complete turnover of air every 10 minutes) Five oxygenation conditions were used: humidified high-flow nasal cannula (HFNC) at 3 flow rates [15, 30, and 60 liters per minute (LPM)], non-rebreather mask (NRB) at 1 flow rate (15 LPM), and closed-circuit continuous positive airway pressure (CPAP) using the ED ventilator;in all cases a simple procedural mask was used The NRB and HFNC at 30 LPM maneuvers were also repeated without the procedural mask, and CPAP was applied both with and without a filter Each subject then sequentially underwent 8 total oxygenation conditions, always in the same order Each oxygenation condition was performed with the participant on a standard ED bed Particles were measured by laser aerosol spectrometer, with the detector sampling port positioned directly over the center of the bed, 0 35 meters away and at a 45-degree angle from the subject's mouth Each approach to oxygenation was performed for 10 minutes, followed by a 20-minute room washout (= 2 complete room air turnovers) Particle counts were summated for 2 size ranges (150-300 nm and 0 5-2 0 mum) and compared before, during, and after each of the 8 oxygenation conditions Results: Eight adult subjects were enrolled (mean age 42 years, body mass index 25) All subjects completed 8 oxygenation procedures (64 total) Mean particle counts per minute across all oxygenation procedures was 379 +/- 112 (mean +/- SD) for smaller aerosols (150-300 nm) and 9 3 +/- 4 6 for larger aerosols (0 5-2 0 mum) HFNC exhibited a flow-dependent increase in particulate matter (PM) generation-at 60 LPM, HFNC had a substantial generation of small (55% increase) and large particles (70% increase) compared to 15 LPM CPAP was associated with lowered small and large particle generation (= 10-15% below baseline for both sizes of PM) A patient mask limited particle generation with the NRB, where it was associated with a reduction in small and large particulates (average 40% and 20% lower, respectively) Conclusion: Among 3 standard oxygenation procedures, higher flow rates generally were associated with greater production of both small and large aerosols A patient mask lowered aerosol counts in the NRB only Protocol development for oxygenation application should consider these factors to increase health care worker safety
Defining a pharmacological inhibitor fingerprint for oxytosis/ferroptosis

Ferroptosis was first described in 2012 as an iron- and lipid peroxidation-dependent form of regulated cell death. Since its initial description, these two characteristics have informed numerous cell culture studies where inhibitors of lipid peroxidation and/or iron chelators have been shown to prevent cell death induced by a wide range of insults. However, it is not clear whether these two characteristics are sufficient to distinguish ferroptosis from other forms of regulated cell death. Thus, the primary goal of this study was to determine whether a unique combination of features could be identified that would provide an approach to more clearly separate ferroptosis from other forms of regulated cell death. To this end, multiple pharmacological inhibitors based on a variety of studies were tested. Many of these inhibitors were previously shown to protect cells from oxytosis, a regulated cell death pathway that mechanistically overlaps with ferroptosis and is induced by some of the same chemicals as ferroptosis. These inhibitors were not only tested against both known ferroptosis and oxytosis inducers but also a number of other insults that have been suggested to induce ferroptosis. The results show that a pharmacological fingerprint for ferroptosis can be established and used to categorize toxic insults into those that overlap with oxytosis/ferroptosis and those that do not.
Mitigating childhood food insecurity during COVID-19: a qualitative study of how school districts in California's San Joaquin Valley responded to growing needs.

OBJECTIVES: To explore best practices and challenges in providing school meals during COVID-19 in a low-income, predominantly Latino, urban-rural region. DESIGN: Semi-structured interviews with school district stakeholders and focus groups with parents were conducted to explore school meal provision during COVID-19 from June to August 2020. Data were coded and themes were identified to guide analysis. Community organisations were involved in all aspects of study design, recruitment, data collection and analysis. SETTING: Six school districts in California's San Joaquin Valley. PARTICIPANTS: School district stakeholders (n 11) included food service directors, school superintendents and community partners (e.g. funders, food cooperative). Focus groups (n 6) were comprised of parents (n 29) of children participating in school meal programmes. RESULTS: COVID-19-related challenges for districts included developing safe meal distribution systems, boosting low participation, covering COVID-19-related costs and staying informed of policy changes. Barriers for families included transportation difficulties, safety concerns and a lack of fresh foods. Innovative strategies to address obstacles included pandemic-electronic benefits transfer (EBT), bus-stop delivery, community pick-up locations, batched meals and leveraging partner resources. CONCLUSIONS: A focus on fresher, more appealing meals and greater communication between school officials and parents could boost participation. Districts that leveraged external partnerships were better equipped to provide meals during pandemic conditions. In addition, policies increasing access to fresh foods and capitalising on United States Department of Agriculture waivers could boost school meal participation. Finally, partnering with community organisations and acting upon parent feedback could improve school meal systems, and in combination with pandemic-EBT, address childhood food insecurity.
The Poeta-Theologus from Mussato to Landino

AbstractFundamental to the modern conception of historical perspective was the position that nature had its own integrity and that a common human nature underlay human action in history. The first tenet was an achievement of the Scholastics, the second of Italian humanists of the fourteenth century. In order to justify the reading of ancient pagan texts an early humanist Albertino Mussato (1261–1329) had resorted to the late ancient and medieval tradition that the pagan poets had been divinely inspired to predict the coming of Christ and a number of other revealed truths. Subsequently, however, Petrarch (1304–74), Boccaccio (1310–75), and Salutati (1332–1406) argued that if poetic genius was a divine gift to individuals, poetic creation was a product of human effort. The consequent desanctification of the ancient writers allowed them to be approached as historical human beings. Nevertheless, the new enthusiasm for Plato beginning with Bruni (1370–1444) initiated a retreat from this position and a return t...
Control relevant model selection for uncertain processes

In process identification, it is common practice to seek the model that minimizes the variance of the data from the model. If the process parameters actually vary over a range, the authors show that choosing a model in the middle of the range is not generally best from a control perspective. The authors use M/sub p/-synthesis (Laiseca and Brosilow, 1992) to obtain models for optimal control system performance for three uncertain processes: 1) a second order process with uncertainty in time constant and damping ratio, 2) an overdamped second order plus dead time process and, 3) a non-collocated spring mass system.
Mechanism for the Pyridoxal Neutralization of Isoniazid Action on Mycobacterium tuberculosis

Abstract In Sauton's synthetic liquid medium, 10 μg of pyridoxal per ml completely protected Mycobacterium tuberculosis (H37Ra) from the effects of a minimal inhibitory concentration of isoniazid (0.01 μg/ml). 14C-labeled isoniazid was employed to study the nature of this protective effect. Uptake of the drug by cells in a Sauton environment containing 0.01 μg of 14C-isoniazid per ml was inhibited 20 to 40% by 10 μg of pyridoxal per ml during the early hours of drug exposure. A stronger inhibition of uptake resulted when labeled isoniazid and pyridoxal were increased to 0.1 μg/ml and 50 to 100 μg/ml, respectively. Further studies revealed that certain Sauton nutrients are required to achieve this effect. When l-asparagine or salts (MgSO4 and ferric ammonium citrate) or both were deleted from the menstruum, pyridoxal did not inhibit isoniazid incorporation by the tubercle bacilli. Pyridoxal also failed to inhibit uptake when (NH4)2SO4 was substituted for l-asparagine. Growth experiments in Sauton's medium modified to contain (NH4)2SO4 instead of l-asparagine were consistent with the latter finding. Pyridoxal did not prevent isoniazid growth inhibition in this medium. It is postulated that a large excess of pyridoxal in Sauton's medium protects tubercle bacilli from the effects of isoniazid through formation of an extracellular complex involving drug, vitamin, and certain medium constituents, thereby reducing the level of isoniazid available to the cells.
ID: An Incremental ID3

THIS PAPER DESCRIBES ID5, AN INCREMENTAL ALGORITHM THAT PRODUCES DECISION TREES SIMILAR TO THOSE BUILT BY QUINLAN''S ID3. THE PRINCIPAL BENEFIT OF ID5 IS THAT NEW TRAINING INSTANCES CAN BE PROCESSED BY REVISING THE DECISION TREE INSTEAD OF BUILDING A NEW TREE FROM SCRATCH. ID3, ID4, AND ID5 ARE DESCRIBED IN DETAIL, COMPARED, AND CONTRASTED. EXPERIMENTS ILLUSTRATE OBSERVED PERFORMANCE IN TERMS OF TRAINING EXPENSE AND CLASSIFI- CATION ACCURACY.
Oral antihistamine/decongestant/analgesic combinations for the common cold.

Combination cold medications, including antihistamine/decongestant/analgesic, antihistamine/decongestant, antihistamine/analgesic, and analgesic/decongestant formulations, provide modest symptom relief in adults and older children, but are not effective in young children. Only the analgesic/ decongestant formulation is associated with a statistically significant increased risk of adverse effects.
Effects of Psychosocial Interactions at a Cellular Level

Psychosocial interactions can affect physiological functions at a cellular level, resulting in increased longevity for people who have had heart attacks or who have acquired immune deficiency syndrome or cancer as well as for healthy individuals. Although social work pioneers and practitioners have always believed that social work intervention can help people feel better, recent studies show that the benefits can be measured quantitatively and qualitatively. In fact, these studies show that lack of psychosocial interaction may be a risk factor for disease progression.
Evidence for a sex pheromone in the hide beetle,Dermestes maculatus (De Geer) (Coleoptera: Dermestidae)

Adults of the hide beetle,Dermestes maculatus (De Geer), were shown to have a female-produced sex pheromone which excited males. Male response was positively correlated with increasing age, but females produced a higher level of pheromone at 6–8 days of age than at younger or older ages. Extractable female pheromone and male response varied over the photophase with peak values that occurred during the latter hours. Quantitative bioassay indicated that the 50% male response level (RD50) would be elicited by a pheromone exposure of 0.01 female equivalents (FE). Females extracted 24 hr after mating had a lower level of extractable pheromone than did virgin females of the same age.
Finite-dimensional points of continuity of Gen and Com

Abstract If A is a linear transformation on a finite-dimensional vector space V , there are two algebras that are naturally associated with A : Gen A , the algebra generated by A and the identity transformation; and Com A , the commutant of A , consisting of all linear transformations T such that AT = TA . This paper studies Gen and Com as functions and, for naturally defined topologies on their domain and range, proves that the following are equivalent conditions on A : (a) Gen is continuous at A ; (b) Com is continuous at A ; (c) A is nonderogatory (or cyclic).
Concurrent oxidation of cholesterol and corn oil sterols in autoxidizing lipid films

A new, simple method based on assay of cholesterol is presented for study of the time course and extent of air oxidation of cholesterol. Using such a method, the air oxidation of 0.5–3.5% solutions of corn oil sterols and cholesterol in films of either corn oil or corn oil fatty acids has been followed by the author for periods of up to 3 months at room temperature and 2 weeks at 60°C. in the dark. Under these conditions it was shown that a) solid cholesterol is relatively stable to air oxidation; b) in lipid films cholesterol is readily subject to oxidative attack which appears to be closely linked to the stability of the lipid film itself to autoxidation; c) more than 90% conversion of cholesterol to oxidation products has been observed in such systems; d) the principal corn oil sterols are oxidized at the same rate as cholesterol, and esterification of the corn oil sterols did not affect the rate at which they were oxidized; and e) the rate of concurrent oxidation of cholesterol in corn oil and corn oil fatty acid films in independent of the concentration of cholesterol at low concentrations, 0.5–3.5%. The disappearance rate is dependent on the stability of the lipid film itself as shown by peroxide value.
Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans.

Amyloid beta (Aβ) peptides, and in particular Aβ42, are found in senile plaques associated with Alzheimer's disease. A compartmental model of Aβ production, exchange and irreversible loss was recently developed to explain the kinetics of isotope-labeling of Aβ peptides collected in cerebrospinal fluid (CSF) following infusion of stable isotope-labeled leucine in humans. The compartmental model allowed calculation of the rates of production, irreversible loss (or turnover) and short-term exchange of Aβ peptides. Exchange of Aβ42 was particularly pronounced in amyloid plaque-bearing participants. In the current work, we describe in much greater detail the characteristics of the compartmental model to two distinct audiences: physician-scientists and biokineticists. For physician-scientists, we describe through examples the types of questions the model can and cannot answer, as well as correct some misunderstandings of previous kinetic analyses applied to this type of isotope labeling data. For biokineticists, we perform a system identifiability analysis and a sensitivity analysis of the kinetic model to explore the global and local properties of the model. Combined, these analyses motivate simplifications from a more comprehensive physiological model to the final model that was previously presented. The analyses clearly demonstrate that the current dataset and compartmental model allow determination with confidence a single ‘turnover’ parameter, a single ‘exchange’ parameter and a single ‘delay’ parameter. When combined with CSF concentration data for the Aβ peptides, production rates may also be obtained.
Nanoindentation of lithium niobate: hardness anisotropy and pop-in phenomenon

Lithium niobate is a non-centrosymmetric crystal. Due to its non-centrosymmetric nature, the properties such as hardness and fracture toughness are likely to be different on opposite faces of the same wafer. In many wafer production processes such as wiresawing, lapping, and polishing, opposite faces of the wafer are processed simultaneously. Thus, it is important to understand the nature of anisotropy on the opposite faces of the same wafer. As a first step, hardness anisotropy of three common orientations of lithium niobate wafers is studied using nanoindentation technique. The hardness values on opposite faces for the same direction are found to be different for most cases. Lithium niobate exhibits a significant indentation size effect. Lithium niobate also exhibits pop-in phenomenon similar to the pop-in behavior of other materials. The pop-in phenomenon in lithium niobate is dictated by crystallographic orientation.
Personality Characteristics of American Gun-Owners

The purposes of the present study were to explore the reasons behind gun ownership and to gather evidence concerning popular stereotypes of gun-owners. Male gun-owners (n = 37) and a matched sample of nongun-owners (n = 23) reported demographic information, reasons for gun ownership, knowledge about guns, and experience with firearms. Ss also completed several personality inventories. Results indicated that gun-owners differed greatly from nongun-owners in their knowledge and interest in firearms. It appeared that early socialization to guns was a primary factor in firearm ownership. While gun-owners stated that recreation and defense were the primary reasons for owning guns, they also had personalities which were characterized by lower sociability and higher need for power than the nongun-owners. The gun-owners on the average did not exhibit atypical personality characteristics when compared with the nongun-owners or with national norms on the California Psychological Inventory. However, the small sample and the high educational level of gun-owners in this study indicate caution when generalizing these findings.
Soil moisture: A central and unifying theme in physical geography:

Soil moisture is a critical component of the earth system and plays an integrative role among the various subfields of physical geography. This paper highlights not just how soil moisture affects a...
Influence of Alloyed Sn on Adsorption and Reaction of NO on Pt(100) Surfaces

Adsorption and reaction of NO on the (5 × 20)-Pt(100) surface and two Sn/Pt(100) surface alloys have been studied using temperature programmed desorption (TPD) and high-resolution electron energy loss spectroscopy (HREELS). On the (5 × 20)-Pt(100) surface, in the absence of Sn, NO is primarily reversibly adsorbed, and most of the chemisorbed NO desorbs molecularly from the surface during TPD. Approximately 25% of the adsorbed NO monolayer decomposes at temperatures higher than 400 K, and this leads to N2 and O2 desorption from the surface. Alloying Sn into the surface layer of Pt(100) forms two ordered surface alloys having c(2 × 2) and (3√2 × √2)R45°Sn/Pt(100) surface structures with θSn = 0.5 and 0.67 ML, respectively. Alloying reduced the saturation coverage of NO in the chemisorbed monolayer from that on Pt(100) at 100 K, and it also reduced the adsorption energy of molecularly bound NO by more than a factor of 2. Alloyed Sn, which removes all pure-Pt 2-fold bridge and 4-fold hollow sites, completely ...
HYDRAULIC TRANSPORT OF FINE AND COARSE SEDIMENT MIXTURES IN PIPELINES

This paper presents results from a comprehensive laboratory study of the effects of a fine grained sediment (clay) carrier fluid on the hydraulic gradient of sand-sized sediments (600–2,000 microns) in a 103-mm diameter pipeline. Three sand sizes were evaluated in the pipeline: (1) medium sand (670 microns), coarse sand (1,260 microns), and very coarse sand (2,040 microns). Initial experiments were conducted with water as the carrier fluid. Sand concentrations of 0.05, 0.10, 0.20, and 0.30 by volume (Cv) were evaluated. For each sand concentration, the effect of phosphate clay concentrations on the hydraulic gradient was evaluated. The clay carrier fluids exhibited both Newtonian and non-Newtonian fluid properties. Study results indicate that the hydraulic gradient reduction effect resulting from phosphate clay added to sand and water slurries increases with sand concentration, decreases with particle size, and is maximum within the flow range representing maximum solids stratification with bed contact (2...
Improved synthesis of isostearic acid using zeolite catalysts

“Isostearic acids” (IA) are branched-chain fatty acids that are nontoxic and biodegradable in nature. They are predominantly used in cosmetics because of their superior moisturizing properties as they are odorless, provide smooth spreading and a non-tacky feeling when applied onto skin. They can also be used in applications which require excellent thermo-stability and low flow temperature properties. The existing older technology produces IA at low yields, which limits their commercial adoption; thus, new technologies for preparing IA are needed.
Off-season spawning and factors influencing toxicity test development with topsmelt Atherinops Affinis

Three separate groups of adult topsmelt (Atherinops a/finis) were spawned in rotation in laboratory culture over a two-year period to provide larvae for toxicity tests. Size and viability of embryos and larvae produced during the normal summer spawning period (May-August) were compared to those produced during the off season (October-April). Mean embryo viability was relatively high throughout the study (82%), whereas size of larvae varied. Larval size was significantly larger during the summer spawning period than in winter. A 7-d growth and survival toxicity test protocol was developed for topsmelt larvae. Variability of the protocol was assessed over a 12-month period using copper chloride as a reference toxicant. Precision of 12 toxicity tests using copper was high; the intralaboratory C.V. for copper LC50s was 19%. The 7-d larval protocol also gave comparable results in two interlaboratory toxicity tests using copper and complex effluent. This study demonstrates that topsmelt may be spawned throughout the year to provide larvae for toxicity tests and that topsmelt larvae have comparable sensitivity to other larval fishes commonly used in toxicity testing.
Arterial stiffness and gait speed in older adults with and without peripheral arterial disease.

BACKGROUND Central arterial stiffness is increasingly recognized as an important predictor of cardiovascular events and mortality in older adults; however, few studies have evaluated the association of arterial stiffness with mobility decline, a common consequence of vascular disease. METHODS We analyzed the association of pulse wave velocity (PWV), a measure of aortic stiffness, with longitudinal gait speed over 7 years in 2,172 participants in the Health, Aging and Body Composition (ABC) Study (mean age ± s.d. 73.6 ± 2.9 years, 48% men, 39% black). RESULTS In mixed-effects models adjusted for demographics, each s.d. (396 cm/s) higher PWV was associated with 0.015 (s.e. 0.004) m/s slower gait at baseline and throughout the study period in the full cohort (P < 0.001); this relationship was largely explained by hypertension and other vascular risk factors. Among participants with peripheral arterial disease (PAD) (n = 261; 12.7%), each s.d. higher PWV was independently associated with 0.028 (s.e. 0.010) m/s slower gait speed at baseline and throughout the study period (P < 0.01). CONCLUSIONS These findings suggest that aortic stiffness may be especially detrimental to mobility in older adults with already compromised arterial function.
Novel Immunomodulatory Approaches for the Management of Multiple Sclerosis

We provide a focused review of novel immunomodulatory approaches for the treatment of multiple sclerosis, the most common acquired inflammatory demyelinating disease of humans. The requirement for such a review was stimulated by the emerging application of novel oral medications and the need for the practicing physician to place these within the treatment paradigm. We provide a conceptual diagram of our current view of the pathogenesis of demyelination and remyelination in this disorder. In addition, we include a working template on how to use a tier 1 and tier 2 approach to medications as the disease worsens in the individual. We emphasize the approach of treatment based on "individualized medicine," tailored to the specific needs of each patient. In the future, we envision new drugs to enhance remyelination and protect neurons and axons from death in order to promote central nervous system regeneration and repair.
Effect of Test Temperature and Strain Rate on the Yield Stress of Monocrystalline 6H‐SiC

The critical resolved shear stress for activating the (0001) (2110) slip system of monocrystalline 6H-SiC has been determined as a function of test temperature and strain rate via constant-displacement compression tests. Tests were conducted at temperatures between 550 and 1300°C at strain rates of 1.3×10 -4 , 6.3×10 -5 and 3.1×10 -5 s -1 . The current study shows that 6H-SiC crystals can be plastically deformed via relatively modest resolved shear stresses on the basal plane at temperatures as low as 550 °C. For temperatures below 1300 °C for the fast and intermediate strain rates, and for temperatures below 1100 °C for the slow strain rate, the stress exponent n, and the activation enthalpy H were estimated to be (3.0±0.7) and (2.1±0.7) eV, respectively. At higher temperatures at the slowest strain rate, the activation enthalpy was determined to be (4.5±1.2) eV. Subsequent to the deformation tests, transmission electron microscopy (TEM) was used to rationalize some of the results.
Observations of Cloud Condensation Nuclei, Sodium-Containing Particles, Ice Nuclei and the Light-Scattering Coefficient Near Barrow, Alaska

Abstract Measurements of the concentrations of cloud condensation nuclei (CCN), sodium-containing particles (SCP) and ice nuclei (IN), and the aerosol light-scattering coefficient were made near Barrow, Alaska, from 8–28 March 1970. The average concentrations of CCN (at 1% supersaturation) and SCP (in the size range 0.06 to 1.0 μm) were 90 and 0.2 cm−2, respectively, The average concentration of IN at −20°C, measured with an NCAR counter without correcting for internal losses, was 0.15 l−1. The light-scattering coefficient was generally on the order of 5 × 10−5 m−1. Although the SCP concentrations were less than 1% of the CCN concentrations at 1% supersaturation, extrapolation of the CCN spectra down to supersaturations which exist in fogs and stratus indicate that in these situations the SCP probably comprise the majority of the activated CCN. The SCP were probably airborne sea-salt particles; their concentrations increased when open leads, which exposed sea water, were present near the measuring site. U...
Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth.

Hepatocellular carcinoma (HCC) is characterized by a propensity for multifocality, growth by local spread, and dysregulation of multiple signaling pathways. These features may be determined by the tumoral microenvironment. The potential of tumor cells to modulate HCC growth and behavior by secreted proteins has been extensively studied. In contrast the potential for genetic modulation is poorly understood. We investigated the role and involvement of tumor derived nanovesicles capable of altering gene expression, and characterized their ability to modulate cell signaling and biological effects in other cells. We show that HCC cells can produce nanovesicles, exosomes, that differ in both RNA and protein content from their cells of origin. These can be taken up and internalized by other cells, and can transmit a functional transgene. The microRNA content of these exosomes was examined, and a subset that is highly enriched within exosomes was identified. A combinatorial approach to identify potential targets identified transforming growth factor β activated kinase-1 (TAK1) as the most likely candidate pathway that could be modulated by these miRNA. Loss of TAK1 has been implicated in hepatocarcinogenesis and is a biologically plausible target for inter-cellular modulation. We showed that HCC cell derived exosomes can modulate TAK1 expression and associated signaling and enhance transformed cell growth in recipient cells. Conclusion: Exosome mediated miRNA transfer is an important mechanism of inter-cellular communication in HCC cells. These observations identify a unique inter-cellular mechanism that could potentially contribute to local spread, intrahepatic metastases or multifocal growth in HCC.
Structure-function relationships of Ca spark activity in normal and failing cardiac myocytes as revealed by flash photography

We describe the two-dimensional imaging of excitation-induced Ca gradients in isolated myocytes under physiological conditions, using a novel method of flash photography of fluo-3 fluorescence. This method is useful for showing the spatial distribution and reproducibility of rapidly triggered Ca release events, and their relationship to underlying structures. In normal rat myocytes, Ca sparks were evident 6ms after stimulation emerging from around t-tubules, as judged by co-localization with di-8-ANEPPS staining. Gaps in the spark pattern coincided with gaps in di-8-ANEPPS staining. Vacuolar fluo-3 uptake, previously identified as lysosomal, was prominent in some of the gaps, suggesting possible areas of t-tubule turnover. In normal dog myocytes, the beat-to-beat variance of Ca sparks was very low, t-tubular voids were small, and Ca gradients resolved rapidly. In myocytes from dogs with failure induced by rapid pacing, a reduced Ca transient was observed associated with increased areas that were void of sparks and t-tubules, and a greater beat-to-beat spark variance. These abnormalities resulted in a non-uniform spatial distribution of sparks, leading to Ca gradients across the cell that persisted for longer times after stimulation. Such Ca gradients could cause heterogeneous contraction and contribute to contractile failure.
Nanopore Sequencing using a Hidden Markov Model for Base-Calling

Nanopore-based DNA sequencing has many features which recommend it over current state of the art sequencing by synthesis methods; increased read length, reduced sample requirements, and increased speed to name a few. However, the accuracy of base-calling using the electrolytic current has thus far been relatively limited, from both solid-state and biological nanopores. Though part of this is due to the low signal-to-noise ratio, another significant contribution is the base resolution of the nanopore - it does not interrogate a single base at a time, rather the current is influenced by multiple bases at the same time.We suggest using this multi-base interrogation as an advantage rather than a disadvantage - each base in the DNA strand is read multiple times in this circumstance, allowing for improved accuracy. We have implemented a method to decode the electrical signature of 3bp resolution nanopore electrical measurements into a DNA sequence using a hidden Markov model. We produced simulated ionic current for all 64 possible triplets using atomic-resolution Brownian dynamics (BD).Using simulated current signatures, we have been able to demonstrate 98.3% base-calling accuracy for λ DNA, a substantially increased value compared to using only a single-base method (47.1%). When applied to 50kb fragments of the human genome, we found a similar median accuracy level (98.2%). Furthermore, we determined that there is a correlation between the local complexity of the sequence, as measured by Shannon's entropy, and the error rate; lower complexity sequence is more error-prone. Longer sequenced fragments have lower error rate - the more information input into the Markov model, the more effective the algorithm is at decoding the DNA sequence; this is in marked contrast to the dephasing problems endemic to current sequencing by synthesis methods.
The role of plant residues in the retention of cadmium in ecosystems

Abstract Both fresh and partially decomposed residues of plant material from an old field, a deciduous hardwood forest and from under pine trees exhibited a high affinity for Cd ++ . The samples were dried and the degree of adsorption of Cd ++ was assayed using 109 Cd. Using the theory of multiple equilibria (Klotz, 1953) the total number of Cadmium-binding sites ( n ) and the intrinsic association constant (K) were determined. Changes in the magnitude of n with litter decomposition appeared to be associated to some degree with changes in ‘cellulose’ and ‘lignin’ content. The total quantity of exchange sites corresponded to from 0·32 to 0·091 moles Cd/m 2 , depending upon source of litter and degree of decomposition. It is suggested that such material could have a role in smoothing out ambient surges in Cd ++ pollution.
Synthesis of poly(adenosine diphosphate ribose) in synchronized Chinese hamster cells.

Abstract Chinese hamster ovary cells were synchronized by mitotic selection and used to study the relation of poly(adenosine diphosphate ribose) synthesis to DNA synthesis and the different phases of the cell cycle. DNA synthesis was measured in cells rendered permeable to exogenously supplied nucleotides. Poly(ADPR) synthesis was also measured in permeable cells in the presence of both minimum and maximum DNA damage. The maximum DNA damage was produced by treating the cells with saturating concentrations of DNase. As anticipated, the DNA synthesis complex showed its maximum activity during S phase and showed 4–5-fold less activity during the other phases of the cell cycle. The basal level of poly(ADPR) synthesis was elevated during G1, fell to its lowest level during S phase, then increased during G2 and rose to its highest level during G1. The DNase responsive activity of poly(ADPR) synthesis was relatively constant thru the cell cycle but showed a peak at the end of S phase; then the activity decreased during the subsequent G2-M period.
Flooding or systematic exposure in the treatment of extreme social withdrawal in children

Abstract Several children provided social stimuli for treating the extreme social withdrawal of two young boys, one treated by flooding, the other by systematic exposure. To assess the effectiveness of the treatment procedures, within-subject designs were used, consisting of multiple baselines across settings. The results showed that when flooding was introduced in the first setting for the first child, a dramatic increase in interaction from 0 to 60% resulted, with an accompanying decrease in self-talk from 70 to 20%. These behavioral changes did not occur in the second setting until flooding was introduced, when interaction increased form 10 to 40% and self-talk decreased from 85 to 20%. Similar results were obtained with systematic exposure in the second child. Follow-ups of 5 months in the first child and 9 months in the second indicated that the therapeutic gains were maintained. Thus, in treating anxiety-related problems in children in their natural environment either flooding or systematic exposure can be effective.
Systemic reaction to papain in a nonoccupational setting

A patient experienced a severe systemic allergic reaction after ingesting meat tenderizer. Evaluation revealed that the reaction was mediated by IgE antibody to papain, an ingredient of the tenderizer. Papain hypersensitivity has been reported among pharmacists and factory workers exposed to the agent, but few nonoccupational cases have been described. The present case may be the first in which the sensitization appears to have occurred via the gastrointestinal route. Papain-containing products are commonly used throughout our society and papain hypersensitivity may represent an unrecognized cause of allergic symptoms.
High reliability of high power and high brightness diode lasers

We report on continued progress in the development of high power and high brightness single emitter laser diodes from 790 nm to 980 nm for reliable use in industrial and pumping applications. High performance has been demonstrated in nLIGHT’s diode laser technology in this spectral range with corresponding peak electrical-to-optical power conversion efficiency of ~65%. These pumps have been incorporated into nLIGHT’s fiber-coupled pump module, elementTM. We report the latest updates on performance and reliability of chips and fiber-coupled modules. This paper also includes a new chip design with significantly narrower slow-axis divergence which enables further improved reliable power and brightness. Preliminary reliability assessment data for these devices will be presented here as well.
Membrane symmetries and anomalies

Abstract The symmetries of the bosonic membrane are analysed in several gauges. We discuss two Lorentz-covariant gauges, and a new light-cone gauge that reduces the membrane hamiltonian to a quadratic form which is diagonalized by harmonic oscillators. We then discuss in detail the Lorentz-covariant quantization and the algebra of constraints that corresponds to the diffeomorphisms in three dimensions (Diff V3). We introduce an operator product expansion which allows the careful computation of commutators. We find that the subalgebras corresponding to diffeomorphisms of the two-dimensional genus-g membrane surface (Diff Σg) and the area-preserving diffeomorphisms (AP Diff Σg) do not have any anomalies, but the full algebra DiffV3 has operator anomalies which render the quantization inconsistent. We thus conclude that purely bosonic membranes are quantum mechanically inconsistent in any number of dimensions d.
Connexin 26 variants and auditory neuropathy/dys-synchrony among children in schools for the deaf.

Genetic and auditory studies of 731 children with severe-to-profound hearing loss in US schools for the deaf and 46 additional children receiving clinical services for hearing loss ranging from moderate to profound demonstrated that mutations in the connexin 26 (GJB2) and connexin 30 (GJB6) genes explain at least 12% of those with nonsyndromic sensorineural deafness. Otoacoustic emissions (OAEs) testing to detect functional outer hair cells indicated that 76 of the children had emissions and therefore may have (as yet unconfirmed) auditory neuropathy/dys-synchrony (AN/AD). Five of these children with OAEs were GJB2 homozygotes or compound heterozygotes with the genotypes 35delG/35delG, W77X/W77X, 35delG/360delGAG, 35delG/V95M, and V84M/M34T. In particular, unilateral AN/AD was confirmed in a child with moderate hearing loss and the 35delG/V95M genotype. Detecting OAEs in individuals with GJB2 mutations suggests that lack of functional gap junctions as a result of GJB2 mutations does not necessarily destroy all outer hair cell function. © 2005 Wiley-Liss, Inc.
Chemical modification of α2-macroglobulin to generate derivatives that bind transforming growth factor-β with increased affinity

α2-Macroglobulin (α2M) binds a number of cytokines, including transforming growth factor-β1 (TGF-β1) and TGF-β2. The affinity of these interactions depends on the α2M conformation. In this investigation, we treated human α2M with cis-dichlorodiammineplatinum (II) (cis-Pt), a crosslinking reagent that partially `locks' the α2M conformation, and then with methylamine to generate a preparation (α2M-P/M) consisting of stable α2M conformational intermediates. α2M-P/M bound TGF-β1 and TGF-β2 with higher affinity than any other form of α2M studied to date. The equilibrium dissociation constants were 14 and 2 nM for TGF-β1 and TGF-β2, respectively. α2M-P/M, at 100 nM, neutralized the activity of TGF-β1 by about 75% in an endothelial cell proliferation assay. The equivalent concentration of native α2M or methylamine-modified α2M had no effect. These studies demonstrate that the potential of α2M as a cytokine carrier and neutralizer may not be fully realized in either the native or completely activated conformations.
Induction of gastric mucosal cell proliferation by the fungicide captan: role of tyrosine kinases.

Captan (1,2,3,6-tetrahydro-N-trichloromethylthiophthalmide), a widely used fungicide, has been shown to induce carcinoma in the gastrointestinal tract of rodents. However, little is known about the captan induction of early biochemical changes in the gastrointestinal tract. The present investigation examines the changes in gastric mucosal proliferative activity in 2-month-old Fischer 344 rats following a daily injection (s.c.) of captan (100 mgkg body wt.) in DMSO while being infused (osmotic minipump) with the same compound (7.14 mg captankg body wt.h) for 2 weeks. The control rats received the vehicle the same way. The change in proliferative activity was related to tyrosine kinase (Tyr-k) activity and tyrosinespecific phosphorylation of protein(s) in gastric mucosal membranes since these intracellular events are thought to play an important role in proliferation, differentiation and transformation of cells. After 2 weeks of captan administration gastric mucosal DNA synthesis and thymidine kinase activity (indicators of proliferative activity) were increased by 330% (P < 0.025) and 98% (P < 0.025), respectively, when compared with the corresponding controls. Gastric mucosal DNA content was also increased by 90% (P < 0.025) after administration of captan. These increases were associated with about 3-fold rise in Tyr-k activity and 2-fold increase in tyrosine phosphorylation of 6 mucosal membrane proteins with Mr of 105, 90, 60, 55, 48 and 37 kDa. We conclude that captan stimulates gastric mucosal cell proliferation, and activation of Tyr-k and tyrosine phosphorylation of certain membrane proteins may be important in the regulation of this process.
A water‐sensitive thermomechanical transition in a polyimide

The effect of water vapor on a polyimide has been investigated in the temperature region of −190 to 325°C using an automated torsion pendulum. A damping peak, T developes at −122°C (1 Hz) in the thermomechanical spectra of the polymer which is due to water–polymer interactions. The peak intensifies as the humidity of the conditioning atmosphere, at both 30° and at 325°C, increases and attains a limiting value at about 3000 ppmv H2O. The process is reversible. It is concluded that the number of sites in the polymer for interaction with water is low and limited (<0.3 molecule H2O per polymer repeat unit) and, assuming direct proportionality between the intensity of the loss peak and the amount of water adsorbed, that the adsorption of water vapor follows the Langmuir isotherm.
Slow growth of microcracks in hydroxyapatite during aging

Hydroxyapatite (Ca10(PO4)6(OH)2 or HA) is a brittle material that is subject to environmentally assisted slow crack growth. While most slow crack growth studies are carried out after aging, this study examines the slow growth of radial cracks induced by Vickers indentation in dense HA (94 % of theoretical density) during aging in ambient air, where the observed crack growth is consistent with a process in which residual stress drives crack growth. For indentation loads of 0.98, 1.96, 2.94, and 4.91 N, the average radial crack length increased exponentially with time for indentation loads of 0.98, 1.96, 2.94, and 4.91 N, with crack lengths saturating within 1 h following indentation. However, no radial crack growth was observed for 9.81 N loads. The load dependence of radial crack growth is proposed to be linked to the partitioning of residual strain energy by the lateral crack growth, which has not been reported in the literature.