cssi/SciSciGPT-SciSciNet huggingface dataset:
Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits.

Autophagy, the major lysosomal pathway for the turnover of intracellular organelles is markedly impaired in neurons in Alzheimer’s disease and Alzheimer mouse models. We have previously reported that severe lysosomal and amyloid neuropathology and associated cognitive deficits in the TgCRND8 Alzheimer mouse model can be ameliorated by restoring lysosomal proteolytic capacity and autophagy flux via genetic deletion of the lysosomal protease inhibitor, cystatin B. Here we present evidence that macroautophagy is a significant pathway for lipid turnover, which is defective in TgCRND8 brain where lipids accumulate as membranous structures and lipid droplets within giant neuronal autolysosomes. Levels of multiple lipid species including several sphingolipids (ceramide, ganglioside GM3, GM2, GM1, GD3 and GD1a), cardiolipin, cholesterol and cholesteryl esters are elevated in autophagic vacuole fractions and lysosomes isolated from TgCRND8 brain. Lipids are localized in autophagosomes and autolysosomes by double immunofluorescence analyses in wild-type mice and colocalization is increased in TgCRND8 mice where abnormally abundant GM2 ganglioside-positive granules are detected in neuronal lysosomes. Cystatin B deletion in TgCRND8 significantly reduces the number of GM2-positive granules and lowers the levels of GM2 and GM3 in lysosomes, decreases lipofuscin-related autofluorescence, and eliminates giant lipid-containing autolysosomes while increasing numbers of normal-sized autolysosomes/lysosomes with reduced content of undigested components. These findings have identified macroautophagy as a previously unappreciated route for delivering membrane lipids to lysosomes for turnover, a function that has so far been considered to be mediated exclusively through the endocytic pathway, and revealed that autophagic-lysosomal dysfunction in TgCRND8 brain impedes lysosomal turnover of lipids as well as proteins. The amelioration of lipid accumulation in TgCRND8 by removing cystatin B inhibition on lysosomal proteases suggests that enhancing lysosomal proteolysis improves the overall environment of the lysosome and its clearance functions, which may be possibly relevant to a broader range of lysosomal disorders beyond Alzheimer’s disease.
Digital Heterodyne Interferometry

Measurements of optical phase differences have been obtained with resolutions of 1/500 wave rms at 100 kHz data rates using frequency shift interferometry. One implementation of this approach, called the digital heterodyne interferometer, uses Bragg cells to generate the frequency shift, and has been applied extensively to real-time, high precision measurements as well as in limited applications to optical testing. We discuss the fundamentals of this approach and review the applications.
Reconsidering how we treat severe congenital neutropenia

Comment on Rosenberg et al, page [4628][1] In this issue of Blood , an updated analysis of the Severe Chronic Neutropenia International Registry dataset by Rosenberg and colleagues reports an alarming incidence of evolution to MDS/AML in patients who are treated with recombinant G-CSF for extended
Spurious-free dynamic range of linewidth-insensitive coherent AM analogue optical links

The Letter shows that externally-modulated coherent AM optical links are limited by the third-order nonlinearity of the electrooptical modulator (EOM) and the EOM nonlinearity reduces the dynamic range by 5–19 dB from the theoretical limit. When the received optical power is less than 1 mW, these links have a better dynamic range than conventional direct detection links.
On dealing with anomalies in the transfer RNA aminoacylation reaction in partially purified systems.

Abstract Apparent differences in tRNA and aminoacyl-tRNA synthetase complements in tissues undergoing differentiation have frequently been used to support theories of translational control. The validity of at least some of these studies must now be questioned because of anomalies in the tRNA aminoacylation reaction which can lead to incomplete aminoacylation of tRNA. Incomplete acylation of a tRNA mixture could result in different relative amounts of acylated isoaccepting species if acylation rates were not identical for all species. Using common methods of analysis, this situation could lead to misestimation of relative levels of isoacceptors or an inability to detect the presence of minor species. Bonnet and Ebel [Bonnet, J., and Ebel, J. (1972) Eur. J. Biochem. 31 , 335] used a highly purified valyl-tRNA and valyl-tRNA synthetase from yeast to demonstrate the presence of four reactions that occur simultaneously in that system. Herein, I apply the findings of Bonnet and Ebel to a mammalian system in a manner which is representative of attempts to study relative tissue proportions of tRNA isoacceptors. Total complements of tRNAs and the aminoacyl-tRNA synthetases have been partially purified from rabbit liver according to the methods of Yang and Novelli [Yang, W. K., and Novelli, G. D. (1971) in Methods in Enzymology (Moldave, K., and Grossman, L., eds.), Vol. 20, p. 44, Academic Press, New York], probably the most commonly used procedures in the literature. Reaction conditions for tRNA acylation are shown to be modifiable so as to influence the extent of tRNA acylation. Procedures for optimizing the extent of tRNA acylation in such systems are demonstrated, and the unfavorable influence of Tris buffer, a factor not discussed by Bonnet and Ebel, is shown. Finally, examples of altered ratios of isoaccepting species in samples incompletely acylated due to suboptimal reaction conditions are provided.
Instability and large‐scale circulations in a two‐column model of the tropical troposphere

A two-column model of the tropical atmosphere is developed. The two columns are kept in buoyancy equilibrium by mass exchange driven by the inter-column pressure gradient, and diabatic processes are parametrized by highly simplified schemes. This model is used to investigate whether spontaneous large-scale circulations will develop in the tropical atmosphere when (he sea surface temperature and solar radiative forcing are uniform. Such circulations do indeed develop in the model, with ascent in one column and descent in the other, when one of the columns is slightly perturbed from the initial state of radiative-convective equilibrium. A key element of the circulation dynamics is that increased equivalent potential temperature in a column leads to enhanced convection and rainfall in that column, which further increases the equivalent potential temperature there. The latter effect arises because convection enhances surface heat fluxes and decreases outgoing long-wave radiation by virtue of the increase in stratiform cloudiness. These results form an attractive explanation for the observed patchiness of deep convection over warm tropical oceans and suggest that further modelling and observational work be directed towards understanding the budget of equivalent potential temperature in the tropical atmosphere and its relationship to rainfall.
The dynamics of the housing market: A stock adjustment model of housing consumption

The importance of transactions costs and conversion costs in the market for residential housing suggests that the observed housing consumption of an individual household will generally differ from its “equilibrium” level of demand (i.e., the housing consumption freely chosen in a frictionless world, given prices, incomes, and tastes). This paper develops an explicit model of this process and provides estimates of alternative stock adjustment models for two samples of renter households. Desired or “equilibrium” housing demand models are estimated from samples of recent mover households; these demand parameters are then used to estimate the rate of adjustment to household equilibrium. The empirical analysis is replicated for two samples and for two time intervals. The results strongly indicate that there are significant lags in adjustment, even for low income renter households. Failure to account for this dynamic structure may give misleading conclusions about the operation of the housing market in the short run and the effects of public policies.
Secondary hyperaldosteronism stimulates acidification in rat distal colon.

Recent studies from this laboratory have determined that colonic K+ absorption is altered by the PCO2 and by secondary hyperaldosteronism. Partial inhibition by vanadate and mucosal ouabain suggested the operation of an H+/K+ exchange pump. To determine the mechanism of acidification in rat distal colon, we measured in vitro acidification using the pH-stat technique by voltage-clamped segments of colonic epithelium in controls and in the presence of secondary hyperaldosteronism, induced by a sodium-deficient diet. Chronic stimulation with aldosterone resulted in increased mucosal acidification in vitro for at least 2 h. This effect could not be accounted for by lactate production and was not altered by elimination of the aldosterone-induced increase in voltage and short-circuit current with 10 μM amiloride. Studies with inhibitors and ion substitution revealed that mucosal acidification resulted from both Na-dependent and Na-independent mechanisms. Na-dependent acidification was inhibited by ATPase inhibitors and was mediated in part by a luminal Na+/H+ exchanger in the presence of secondary hyperaldosteronism. Na-independent acidification was mediated by a pathway dependent on luminal K+ that was inhibited by vanadate and mucosal ouabain, consistent with the operation of an H+/K+ exchange pump.
Decreased lung metastasis and tumor growth in parenterally fed mice

The influence of alternate forms of nutritional support on primary tumor growth rate, tumor DNA synthesis rate, and number of lung metastases was examined in Swiss mice bearing subcutaneously implanted Lewis lung carcinoma (LLC). From Day 14 through 22 postimplant, mice were fed by continuous intravenous infusion of dextrose/amino acid (TPN), were offered the same solution from a feeding bottle (PO), were offered a casein-based, solid diet (CASEIN), or were infused with an electrolyte (ELECT) solution while energy and nitrogen were provided from the casein diet. Tumor weight and doubling time were decreased in the PO group compared to CASEIN; however, host weight decreased by 22% in the PO group. Tumor weight and DNA synthesis were decreased in the TPN group compared to CASEIN, and host weight increased by 4.6%. The decreased rate of tumor growth in the PO group was not reflected in a decrease in DNA synthesis, perhaps a result of the circadian pattern of DNA synthesis as previously reported for LLC. The number of metastatic lung nodules was significantly decreased in both the TPN and ELECT groups compared to PO and CASEIN, suggesting that intravenous fluid load rather than nutrient intake was the causative factor. In this host-tumor system, parenteral feeding was associated with a decrease in primary tumor weight and DNA synthesis rate, maintenance of host weight, and a decrease in pulmonary metastatic disease compared to mice fed a conventional diet.
Mechanisms of abnormal platelet aggregation in systemic lupus erythematosus

Platelet aggregation was measured in 14 patients with systemic lupus erythematosus (SLE) and 13 normal controls. Ten SLE patients (group I) showed decreased responsiveness to collagen, while aggregation was normal in 4 (group II). Group I patients also responded poorly to epinephrine. Platelets from SLE patients did not differ from controls in the production of malondialdehyde in response to N-ethylmaleimide, suggesting intact prostaglandin synthetic pathways. However, a significant decrease (P less than 0.005) in platelet levels of the dense granule constituent, serotonin, was noted in group I SLE patients. Treatment of SLE platelet-rich plasma with deoxyribonuclease (DNase) resulted in enhancement of collagen-induced aggregation in 4 group I SLE patients, but not in 1 group II or 8 normal individuals. These results suggest that defective aggregation in SLE platelets may be partially related to a storage pool deficiency state. However, the ability to restore aggregation to collagen by digestion of platelet-rich plasma with DNase indicates that the defect is reversible and that it is perhaps mediated by plasma or platelet-associated DNA.
Control of Feed Intake and the Fat Depots

Abstract Energy balance appears to be regulated in many mammals so that growth rate is nearly constant in young animals, and body energy content is nearly constant in mature animals in many environmental and physiological conditions. The results of many experiments indicate that the fat depots, which are the major energy reserve, are maintained at about the same level and may be the basis of energy balance regulation. The control of meal size and frequency requires a hunger-satiety system which involves a composite signal from various receptors for metabolites, gastric function, etc. Factors for the latter system probably vary in the importance in their role with species, diet and environment. The hunger-satiety system and energy balance regulation are interrelated in the control of feeding. In the hypothalamus exists areas which generate a positive input for feeding (e.g., lateral areas) and a negative (or satiety) input for feeding (e.g., ventromedial areas) and which may function as a memory system for energy balance regulation. Many conditions (e.g., caloric dilution, heat stress, disease) can limit feeding and influence energy balance regulation. Most mammals have appropriate sensory cues which can stimulate feeding of often selective feedstuffs. In this review various aspects of the above components of the energy balance regulator are discussed and a scheme is presented to illustrate the many interrelationships.
BPR: Creating the Conditions for Success

Abstract The business process improvement (BPI) literature is replete with advice on how to improve business processes, but what is lacking is a holistic approach that encompasses the most important facets for long-term success—methods to facilitate people, an organizational structure conducive to empowerment, and a systematic method for solving problems. The study offers an in-depth examination of the BPI methodology used by Caterpillar. The case details what Caterpillar has done to make BPI work and offers tips to help other organizations overcome obstacles to BPI success. A theoretical model is developed that offers a conceptual view of holistic BPI.
Diffusion tensor imaging detects axonal injury and demyelination in the spinal cord and cranial nerves of a murine model of globoid cell leukodystrophy.

Globoid cell leukodystrophy is an inherited neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactosylceramidase. In both human patients and the authentic murine Twitcher model, pathological findings include demyelination as well as axonal damage in both the central and peripheral nervous system. Diffusion tensor imaging (DTI) has emerged as a powerful noninvasive technique that is sensitive to these white matter disease processes. Increases in radial diffusivity (λ⊥) and decreases in axial diffusivity (λ||) correlate with histopathological evidence of demyelination and axonal damage, respectively. Compared to age-matched, normal littermates, DTI of optic nerve and trigeminal nerve in end-stage Twitcher mice displayed a statistically significant increase in λ⊥ and decrease in λ|| consistent with previously characterized demyelination and axonal damage in these regions. In the Twitcher spinal cord, a statistically significant decrease in λ|| was identified in both the dorsal and ventrolateral white matter relative to normal controls. These results were consistent with immunofluorescent evidence of axonal damage in these areas as detected by staining for nonphosphorylated neurofilaments (SMI32). Increase in λ⊥ in Twitcher spinal cord white matter relative to normal controls reached statistical significance in the dorsal columns and approached statistical significance in the ventrolateral region. Reduced levels of myelin basic protein were detected by immunofluorescent staining in both these white matter regions in the Twitcher spinal cord. Fractional anisotropy, a nonspecific but sensitive indicator of white matter disease, was significantly reduced in optic nerve, trigeminal nerve, and throughout the spinal cord white matter of Twitcher mice relative to normal controls. This first reported application of spinal cord DTI in the setting of GLD holds potential as a noninvasive, quantitative assay of therapeutic efficacy in future treatment studies.
Biogeochemical classification of South Florida's estuarine and coastal waters.

Abstract South Florida’s watersheds have endured a century of urban and agricultural development and disruption of their hydrology. Spatial characterization of South Florida’s estuarine and coastal waters is important to Everglades’ restoration programs. We applied Factor Analysis and Hierarchical Clustering of water quality data in tandem to characterize and spatially subdivide South Florida’s coastal and estuarine waters. Segmentation rendered forty-four biogeochemically distinct water bodies whose spatial distribution is closely linked to geomorphology, circulation, benthic community pattern, and to water management. This segmentation has been adopted with minor changes by federal and state environmental agencies to derive numeric nutrient criteria.
An electron microscopic examination of VF2

Abstract Samples of blue and black VF 2 , the latter prepared by heating blue VF 2 with VF 3 in a sealed crucible, were examined in the electron microscope. A nonintegral superstructure pattern was observed. Evidence presented supports the hypothesis that this superstructure results from the epitaxial growth of a phase, possibly an oxide, on the surface of the black VF 2 , and upon that of both the blue and black forms of VF 2 in a twinned mode upon electron beam irradiation. The capability of the microscope to facilitate explanation of these unexpected results is discussed.
Coal liquefaction catalysts. The growth of cobalt sulfide particles during use at 450°C

Abstract Co-Mo-Al 2 O 3 catalysts lose activity during use, and while carbon deposition may account for much of the initial activity loss, other factors are responsible for longer term activity decrease. Large crystals of cobalt sulfide, presumably Co 9 S 8 , form during catalyst use in an H-Coal operation. Back-scatter electron micrographs permit an estimation of the rate of formation of these cobalt particles. X-ray diffraction studies confirm, and augment, the formation rate data for these crystalline cobalt sulfide particles. High resolution TEM data confirm that these particles are predominantly cobalt sulfide and do not contain appreciable molbydenum. The cobalt sulfide particles increase, in size or number, for the first fifteen days of the 30 day run and then appear to reach a steady-state that catalyst addition-withdrawal helps maintain. The cobalt sulfide crystal growth appears to parallel the decline in catalyst activity.
Inessential Features, Ineliminable Features, and Modal Logics for Model Theoretic Syntax

While monadic second-order logic (MSO) has played a prominent role in model theoretic syntax, modal logics have been used in this context since its inception. When comparing propositional dynamic logic (PDL) to MSO over trees, Kracht (1997) noted that there are tree languages that can be defined in MSO that can only be defined in PDL by adding new features whose distribution is predictable. He named such features "inessential features". We show that Kracht's observation can be extended to other modal logics of trees in two ways. First, we demonstrate that for each stronger logic, there exists a tree language that can only be defined in a weaker logic with inessential features. Second, we show that any tree language that can be defined in a stronger logic, but not in some weaker logic, can be defined with inessential features. Additionally, we consider Kracht's definition of inessential features more closely. It turns out that there are features whose distribution can be predicted, but who fail to be inessential in Kracht's sense. We will look at ways to modify his definition.
An experimental and theoretical study of the D-region—I. Mid-latitude D-region electron density profiles from the radio wave interaction experiment

In Part I a summary of quiet D-region electron density measurements made by tlie wave interaction technique at The Pennsylvania State University for the period October 1969 through January 1971 is presented. The results include the mean features of noontime electron density profiles as well as the diurnal and seasonal variations. Detailed discussion on the methods of data analysis, including a critical evaluation of errors, is also presented. The results presented in the part form a partial basis for developing the semi-empirical D-region model presented in Part II.
Media Use and Gender Differences in Negative Psychological Responses to a Shooting on a University Campus.

Prior research in responses to crisis and emergency messages has indicated that while the acquisition of information is critical in reducing anxiety and stress, informational needs and associated emotional reactions on the part of men and women may be quite different. This survey study revealed that responses following a campus shooting in 2008 were consistent with this research, as women expressed greater anxiety and desire for information. A ruminative coping style is offered as a possible explanation, and the results are discussed in terms of implications for emergency management.
Markers informative for ancestry demonstrate consistent megabase-length linkage disequilibrium in the African American population

Admixture mapping is a potentially powerful tool for mapping complex genetic diseases. For application of this method, admixed individuals must have genomes composed of large segments derived intact from each founding population. Such segments are thought to be present in African Americans (AA) and should be demonstrable by examination of linkage disequilibrium (LD). Previous studies using a variety of polymorphic markers have variably reported long-range LD or rapid decay of LD. To further define the extent and characteristics of LD caused by admixture in the AA population, the current study utilized a set of 52 diallelic markers that were selected for large standard variances between putative representatives of the founder populations. LD was examined in over 250 marker-pairs, including linked markers from four different chromosomal regions and an equal number of matched unlinked comparisons. In the representative founder populations, strong LD was not observed for markers separated by more than 10 kb. In contrast, results indicated significant LD (P 0.3) in AA over large genomic segments exceeding 10 centiMorgans (cM) and 15 megabases (Mb). Only marginally significant LD was present between unlinked markers in this population, suggesting that choosing appropriate levels of significance for admixture mapping can minimize false positive results. The ability to detect LD for extended chromosomal segments in AA decayed not only as a function of the distance between markers, but also as a function of the standard variance of the markers. This examination of several genomic segments provides strong evidence that appropriate selection of informative markers is a crucial prerequisite for the application of admixture mapping to the AA population.
First Report of White Leaf Streak of Rice Caused by Mycovellosiella oryzae in Texas.

Rice (Oryza sativa L.) plants in experimental plots in Beaumont, TX developed symptoms on leaf blades similar to white leaf streak caused by Mycovellosiela oryzae (Deighton & Shaw) Deighton (synonym Ramularia oryzae Deighton & Shaw) (1,3,4) during the late summer of 2009. Symptoms were observed on several rice cultivars and breeding lines including Cocodrie, Cypress, and Lemont. Lesions usually appeared on lower leaves and were approximately 2 to 7 mm long and linear with whitish or grayish centers surrounded by a narrow brown-or-dark brown margin. Symptoms were similar to narrow brown leaf spot caused by Cercospora janseana (Racib.) O. Const. (synonym C. oryzae Miyake) (3,4), but the centers of lesions were slightly wider (up to 2 mm). Symptoms were visible on the upper and lower leaf surfaces. Some lesions on heavily infected leaves were long (10 to 15 × 0.5 to 2 mm) whitish streaks parallel to the midrib. Leaves with typical symptoms were collected and incubated in a petri dish lined with moistened fil...
Book Writing: Not for the Faint Hearted

Writing a book is a tough process, but the insight and advice provided here offer help on how to get started, select a topic, develop a strong outline, conduct the research, stay on schedule, and get the book finished and published.
CRT-128 Safety of Rotational Atherectomy in High Risk PCI with Hemodynamic Support

Rotational atherectomy (RA) can aid in high risk Percutaneous Coronary Intervention (PCI) with hemodynamic support. There is concern that use of RA could result in increased procedural complications. We report our institution’s experience with RA in high risk PCI with hemodynamic support. 398
A physiological study of byssinosis in colonial America.

We assessed the acute effects of inhalation of flax dust, produced during processing of flax fibers under conditions similar to those in colonial America. Exposure to this dust, for about 5 hours, caused minor symptoms of chest tightness in five healthy persons, accompanied by decreases of maximum expiratory flow rates, indicating acute small airway obstruction. Measurements of flow rates on partial expiratory flow-volume (PEFV) curves were more sensitive than flow rates on MEFV curves and FEV1.0 in assessing constrictor effects of flax dust, even though flow rates on flow-volume curves are more variable under control conditions than the FEV1.0. Thus, acute symptoms of byssinosis may have been prevalent among early settlers in America who processed flax in their barns. Since these barns were used for many other purposes as well, children and other farm workers were probably also at risk. Ramazzini's observations on the flax and hemp workers of Northern Italy were, for obvious reasons, not accompanied by objective evidence concerning the effects of flax and hemp dust on the lungs. Since 17th-century working conditions are being recreated in historical restoration projects, and modern function tests are available, such objective evidence can now be obtained. With the revival of primitive crafts in our times, this is of some practical importance. The primitive methods used for fiber processing in Ramazzini's time are demonstrated every day at Philipsburg Manor, North Tarrytown, New York. Philipsburg Manor is a restoration project, dedicated to a historical interpretation of life among early Dutch settlers in the Hudson Valley. A recent field study on this site provided an opportunity to assess the acute effects of flax dust on the lungs of people who process flax fibers with primitive methods and on the lungs of others who are exposed to flax dust in the same environment.
Probing the size and density of silicon nanocrystals in nanocrystal memory device applications

Structural characterization via transmission electron microscopy and atomic force microscopy of arrays of small Si nanocrystals embedded in SiO2, important to many device applications, is usually difficult and fails to correctly resolve nanocrystal size and density. We demonstrate that scanning tunneling microscopy (STM) imaging enables a much more accurate measurement of the ensemble size distribution and array density for small Si nanocrystals in SiO2, estimated to be 2-3 nm and 4 x 10^(12) - 3 x 10^(13) cm^(-2), respectively, in this study. The reflection high energy electron diffraction pattern further verifies the existence of nanocrystallites in SiO2. The present STM results enable nanocrystal charging characteristics to be more clearly understood: we find the nanocrystal charging measurements to be consistent with single charge storage on individual Si nanocrystals. Both electron tunneling and hole tunneling processes are suggested to explain the asymmetric charging/ discharging processes as a function of bias.
A holistic approach to the critically ill and Maslow's hierarchy

Safety—in Maslow's hierarchy, this stage is described as security, stability, and freedom from fear. Therefore, once physiological stability is achieved, we must address psychological safety. In the ICU, this may be accomplished by preventing hallucinations/ delusions/delirium. Therefore, we propose activation of patient's consciousness via discontinuation of sedation, concomitantly with directing patients' consciousness toward perception of reality, and engaging them in early physical rehabilitation to mobilize the body and the brain. Psychological safety can be achieved only once a patient gains an accurate perception of reality. Love/belonging—ICU personnel and family need to provide the patient with moral support and reassurance, as well as maintain an adequate perception of reality from the prior stage. Self-esteem—in Maslow's hierarchy, this stage represents independence and achievement of a task that results in positive selfesteem.In the ICU, the“task”of thepatientisphysicalandneuropsychological recovery, moving toward functional independence. ICU personnel and family need to promote respect and positive selfesteem to facilitate recovery, and to prevent formation of negative self-assessment. Self-actualization—in the ICU, this stage involves preparation of the patient by ICU personnel and family members for life after the ICU, with recognition that the patient received a second chance to live, after life-threatening illness. The focus should be on building a new life and new opportunities. Self-actualization, in this context, involves finding oneself in that new life. In this adaptation of Maslow's hierarchy, ICU personnel, family members, and the patient play an active part in each of the stages after physiological stabilization. Application of Maslow's hierarchy in the ICU can facilitate recovery of the interconnection between the body and mind of the patient. The return of patients to their premorbid level of functioning is feasible only when both the body and mind are restored and can work together.
Recent Advances in Pharmacotherapy

Many unique and clinically important medications were approved by the Food and Drug Administration from December 2007 through May 2008 for various conditions encountered in an internal medicine setting. These new treatments dramatically vary in their targeted body system and include agents for the cardiovascular system (nebivolol), central nervous system (desvenlafaxine), gastrointestinal tract (certolizumab, methylnaltrexone, and alvimopan), immunological function (etravirine), and metabolic function (sapropterin). This article discusses medications by their respective body system. Each review is comprised of an overview of the Food and Drug Administration–approved indication and the drug’s role in treatment of that disease state. Current dosing guidance, clinical efficacy and clinically relevant adverse drug reactions, drug interactions, contraindications, and precautions are also presented. This review is designed to focus on the new molecular entities and biological approvals clinicians may potentiall...
Protonophore antagonism of botulinum toxin in mouse muscle

Botulinum neurotoxins (BoNT) are thought to enter cells through endocytotic vesicles where acidification is required for release of these toxins into the cytoplasm. Two ionophores, nigericin and monensin, that increase membrane permeability to H+ and K+ or H+, Na+ and K+, respectively, block vesicle acidification by acting as H+ shunts to neutralize pH gradients. Nanomolar concentrations of nigericin or monensin delayed development of blockade in BoNT-A or BoNT-B treated muscles two-to threefold over onset times in unprotected muscles. However, higher concentrations of the ionophores directly blocked synapses. Thus, nigericin and monensin could delay onset of BoNT paralysis only over a narrow range of concentrations.
Situational and Individual Determinants of Teachers' Reported Use of Behavior Alteration Techniques

Tying together principles applicable to compliance-gaining from both interpersonal and instructional communication theory and research, this investigation focused on situational and individual difference determinants of teachers’ strategy selection in the classroom. Specifically, this study required teachers to focus on student misbehavior scenarios that reflected the situational determinants of misbehavior type (active/passive) and intensity (moderate/severe). Results indicated that teachers’ compliance-gaining message selection was influenced substantially by misbehavior type, and to a lesser extent, misbehavior intensity. Assessments of teachers’ and students’ gender confirmed stereotypic differences for male and female teachers’ reported technique use, but no student gender effect was obtained. These findings are compared with those obtained with prospective teachers (Plax, Kearney, & Tucker, 1986). Results are discussed in terms of cognitive scheme development for classroom management.
The Medicine of Coming to Center: Use of the Native American Centering Technique—Ayeli—to Promote Wellness and Healing in Group Work

This article provides group counselors a description of Ayeli, a culturally-based centering technique rooted in Native American traditions. Ayeli is a process that allows participants an opportunity to experience and reflect on four crucial elements relevant to wellness from a Native American perspective: belonging, mastery, independence, and generosity. Clients are encouraged to explore visually, introspectively, and interpersonally how they would like to find greater balance and harmony in their lives along these four dimensions essential for wellness. Ayeli is described as relational, helping group members to find the source of harmony with self, family, community, environment, and the spiritual world.
Role of embryo transfer in fellowship training

Our objective was to survey training in ET techniques among fellows, its perceived importance, and potential barriers to ET training during fellowship. Although ET training remains an important issue for most fellows and recent graduates, 44% of respondents did not receive this training during their fellowship.
Environmental justice, sustainability and vulnerability

Justice is a core yet often ignored principle of sustainability. However, sustainability for some at the expense of others undermines the principles and practice of sustainability as a force for positive change. In this commentary, I argue that sustainability research and practice can benefit from a closer reading of environmental justice scholarship. At the same time, environmental justice can draw on sustainability principles of systems thinking, anticipatory action and environmental stewardship to strengthen its methods and approaches while broadening its constituency. Vulnerability science can bridge environmental justice and sustainability and can also benefit from the convergence of ideas, principles and practices of these fields.
Two-Dimensional Image Processing By One-Dimensional Filtering Of Projection Data

Two-Dimensional (2-D) inputs can be reduced to a set of 1-D functions by projection coding. Two-dimensional (2-D) operations can be implemented by the appropriate processing of these 1-D distributions. This paper discusses two possible projection coding methods and describes the operations and hardware necessary to measure the 1-D functions, process them, and reconstruct the desired 2-D distribution.
Commentary: a plausible model.

One widely expressed K+ channel, often called the “BK” channel for its “big” single channel conductance, is regulated by intracellular Ca2+ and voltage: at constant voltage, the open probability (Po) increases with [Ca2+]. At constant [Ca2+], Po increases with depolarization. BK channels participate in many physiological processes, including repolarization of the action potential (Adams et al. 1982), frequency tuning in the inner ear (Hudspeth and Lewis 1988), and regulation of neurotransmitter release (Robitaille et al. 1993). The mechanism of BK channel gating is addressed by a recent paper in this journal (Rothberg and Magleby 1999) and by two papers in this issue (Horrigan et al. 1999; Horrigan and Aldrich 1999). The Magleby and Aldrich labs took very different approaches, but fortunately arrive at compatible conclusions. Rothberg and Magleby 1999 examined in detail the gating of single BK channels under a limited range of conditions: +30 mV, primarily at saturating [Ca2+]. Horrigan et al. 1999 and Horrigan and Aldrich 1999 examined macroscopic ionic and gating currents (respectively), over a wide voltage range but in the effective absence of [Ca2+]. Both find features of BK channel gating that favor allosteric models, resembling in some ways the classical MWC model (Monod et al. 1965) for activation of allosteric enzymes.
Effect of Solid Solution Impurities on Dislocation Nucleation During Nanoindentation

Dislocation nucleation in solid solutions of face-centered-cubic metallic materials was studied using nanoindentation. The effects of solute impurities in the copper–nickel system on the formation of dislocations in a previously dislocation-free region were demonstrated to be minimal. The shear stress required to nucleate dislocations in copper is approximately 1.6 GPa, while in nickel a 3.9 GPa shear stress is required. Changes in shear stress for nucleation track closely with changes in elastic modulus showing the nucleation stress is approximately 1/30 to 1/20 of the shear modulus. The expected solid-solution strengthening is identified within the same experimental method, demonstrating unambiguously the fact that solid-solution impurities in this system will impact the propagation of dislocations during plastic deformation but not alter the homogeneous nucleation of dislocations in these materials.
Evaluating the profitability of site-specific farming

Site-specific farming (SSF) practices are being adopted at an accelerating rate, but evidence of their profitability has been mixed or missing. This contribution evaluates the profitability of SSF practices by synthesizing quantitative and qualitative research results within the context of the economics of information technology. The profitability results from nine published field research studies on variable rate (VR) fertilizer application are reviewed using partial budgets adjusted to include minimum costs and grid cell areas for each study. Profitability results correlated closely with the gross revenue earning potential of the crop, so VR fertilizer application was unprofitable on wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.), sometimes profitable on corn (Zea mays L.), and profitable on sugarbeet (Beta vulgaris subsp. L. vulgaris). Although the formal published literature has ignored the profitability of yield mapping, production economics and farmer interviews suggest that yield mapping is profitable when it reveals yield patterns that can be managed at acceptable cost and when the information has compensating off-field value. Manageable yield variability includes not only VR input management, but also whole-field improvements such as field drainage, land leveling, windbreaks, and fencing. Off-field value can come from cheaper on-farm experimentation and greater negotiating power with landlords. Farmers and agribusinesses committed to field crop production for the long term should develop SSF capabilities. But because SSF practices are site-specific, their profitability potential too is site-specific. This site specificity extends beyond the farm field to the crop rotation, and the capabilities and opportunities available to the farm or agribusiness manager.
All peptide-MHC complexes are not created equal.

Spacial organization of membrane components can facilitate productive interactions between T cells and APCs. New data suggest that specific peptides are clustered within APC tetraspan microdomains that are more efficient in evoking T cell responses.
The clinical significance of amenorrhea as a diagnostic criterion for anorexia nervosa.

Objective: Amenorrhea is a DSM-IV criterion for the diagnosis of anorexia nervosa (AN). Several studies have reported few differences between patients who meet the full DSM-IV criteria for AN and those who meet all but the amenorrhea criterion. Although this suggests that the absence of menses does not provide critical diagnostic information, many of these studies are limited by small sample sizes. This study aims to examine the clinical utility of amenorrhea as a criterion for the diagnosis of AN. Method: A chart review was conducted of 240 consecutive patients admitted for inpatient treatment at the NY State Psychiatric Institute from 1993 to 2006. Menstrual data were collected from the Eating Disorder Examination conducted upon admission. Independent samples t-tests were performed to evaluate differences in clinical variables, including age, lifetime lowest body mass index (BMI), admission and discharge BMI, previous number of hospitalizations, duration of illness, Beck Depression Inventory total score, Beck Anxiety Inventory total score, and Eating Disorder Examination subscale scores. Results: The amenorrheic and menstruating groups differed significantly only on lowest lifetime BMI and admission BMI, with individuals with amenorrhea having lower BMIs on both measures. Conclusion: These results indicate that amenorrhea does not distinguish between groups on a number of important measures of clinical severity. It may be that amenorrhea reflects weight and nutritional status, rather than providing useful diagnostic information. Future studies are needed to examine the potential prognostic value of menstrual status. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008
CCR 20th Anniversary Commentary: Radioactive Drones for B-cell Lymphoma

In a study published in the March 1, 1996, issue of Clinical Cancer Research , Knox and colleagues (1) demonstrated the safety and efficacy of Yttirium-90 ( 90 Y)-anti-CD20 monoclonal antibody therapy, as well as the benefit of preinfusion of unlabeled antibody on radiolabeled antibody biodistribution. Subsequent clinical trials with this radiolabeled antibody led to regulatory approval of this treatment for B-cell lymphoma. Clin Cancer Res; 21(3); 493–4. ©2015 AACR . See related article by Knox et al., Clin Cancer Res 1996;2(3) Mar 1996; 457–70
Representation, Salience, and Responsiveness to Latino Student Performance

This article is interested in the implications political representation and issue salience have for political attentiveness to group-specific (Latino) policy failures. Using data from Texas school districts, this article examines the role descriptive political representation plays in the likelihood of recognizing and responding to policy outcomes that disproportionately negatively affect Latino students. The empirical results suggest that deficiencies in Latino student education are significantly more likely to be recognized if Latinos are present on the school board. This suggests that political representation plays a crucial role in the political assessment process, particularly when the policy is not universally salient.
Characterization of Nonspecific Protein−DNA Interactions by 1H Paramagnetic Relaxation Enhancement

Nonspecific protein-DNA interactions play an important role in a variety of contexts related to DNA packaging, nucleoprotein complex formation, and gene regulation. Biophysical characterization of nonspecific protein-DNA interactions at the atomic level poses significant challenges owing to the dynamic nature of such complexes. Although NMR spectroscopy represents a powerful tool for the analysis of dynamic systems, conventional NMR techniques have provided little information on nonspecific protein-DNA interactions. We show that intermolecular (1)H paramagnetic relaxation enhancement (PRE) arising from Mn(2+) chelated to an EDTA-group covalently attached to a thymine base (dT-EDTA-Mn(2+)) in DNA provides a unique approach for probing the global dynamics and equilibrium distribution of nonspecific protein-DNA interactions. For nonspecific DNA binding, similar intermolecular (1)H-PRE profiles are observed on the (1)H resonances of the bound protein when dT-EDTA-Mn(2+) is located at either end of a DNA oligonucleotide duplex. We demonstrate the applicability of this approach to HMG-box proteins and contrast the results obtained for nonspecific DNA binding of the A-box of HMGB-1 (HMGB-1A) with sequence-specific DNA binding of the related SRY protein. Intermolecular (1)H-PRE data demonstrate unambiguously that HMGB-1A binds to multiple sites in multiple orientations even on a DNA fragment as short as 14 base pairs. Combining the (1)H-PRE data with the crystal structure of the HMGB-1 A-box/cisplatin-modified DNA complex allows one to obtain a semiquantitative estimate of the equilibrium populations at the various sites.
Effect of Bowel Resection on Lower Esophageal High Pressure Zone and Reflux Status in Rhesus Monkeys

Giles et al. [5] in 1969 and Caste11 and Harris [2] in 1970 have shown that gastrin has a tonic effect on the lower esophageal high pressure zone (HPZ). The physiologic significance, if any, of the influence of hormones on the gastroesophageal junction remains the subject of much controversy. Massive bowel resection increases gastric acid secretion, presumably by a humoral mechanism. Recently serum gastrin has been shown to be significantly elevated under these circumstances in both dog [16] and man [ 141. We investigated the effect of altering the humoral milieu by 50% small bowel resection on the HPZ pressure and functional integrity of the lower esophagus. The animal model used was the subhuman primate Macaca mulatta.
Expanded view of universities would be more realistic

Tertiary education is poised for greater changes during the next decade than John Hennessey's vision implies (Nature 463, 26–32; 2010). The rising demand for university education in the developing world could affect universities in developed countries. Western universities, for example, could help fill huge gaps in faculties in China, India and countries in southeast Asia, Africa and South America. Greater international cooperation and more study programmes abroad are likely to feature. Distance learning could become more popular, particularly in remote areas. Open-course material, such as that pioneered by the Massachusetts Institute of Technology, might warrant further development. And modified programmes for professional degrees, such as a one-year Master of Business Administration, could become more widespread.
Fabrication of internally tapered capillaries for capillary electrochromatography electrospray ionization mass spectrometry.

In this study, we report a novel procedure for fabricating internally tapered capillary columns suitable for the coupling of capillary electrochromatography (CEC) to electrospray mass spectrometry (ESI-MS). The internal tapers were prepared by slowly heating the capillary end in a methane/O2 flame. Due to continuous self-shrinking of the inner channel of the capillary, the inside diameter of the opening was reduced to 7−10 μm. The procedure is easy to handle, with no requirement for expensive equipment as well as elimination of problematic grinding of the tip. Several advantages of these new internal tapers, as compared to using externally tapered columns, are described. First, the problems of poor durability and tip breakage associated with external tapering were successfully overcome with the internal taper. A comparison of the online CEC/ESI-MS between external versus internal tapers showed that the latter provides enhanced electrospray stability, resulting in significantly lower short-term noise and v...