cssi/SciSciGPT-SciSciNet huggingface dataset:
Immunogold electron microscopic evidence of differential regulation of GluN1, GluN2A and GluN2B, NMDA-type glutamate receptor subunits in rat hippocampal CA1 synapses during benzodiazepine withdrawal

Benzodiazepine withdrawal-anxiety is associated with enhanced AMPA receptor (AMPAR)-mediated glutamatergic transmission in rat hippocampal CA1 synapses due to enhanced synaptic insertion and phosphorylation of GluA1 homomers. Interestingly, attenuation of withdrawal-anxiety is associated with a reduction in NMDA receptor (NMDAR)-mediated currents and subunit expression, secondary to AMPA receptor potentiation. Therefore, in this study ultrastructural evidence for possible reductions in NMDAR GluN1, GluN2A and GluN2B subunits was sought at CA1 stratum radiatum synapses in proximal dendrites using postembedding immunogold labeling of tissues from rats withdrawn for 2-days from 1-week daily oral administration of the benzodiazepine, flurazepam (FZP). GluN1-immunogold density and the percentage of immunopositive synapses were significantly decreased in tissues from FZP-withdrawn rats. Similar decreases were observed for GluN2B subunits, however the relative lateral distribution of GluN2B-immunolabeling within the postsynaptic density did not change after BZ withdrawal. In contrast to the GluN2B subunit, the percentage of synapses labeled with the GluN2A subunit antibody and the density of immunogold labeling for this subunit was unchanged. The spatial localization of immunogold particles asssociated with each NMDAR subunit was consistent with a predominantly postsynaptic localization. The data therefore provide direct evidence for reduced synaptic GluN1/GluN2B receptors and preservation of GluN1/GluN2A receptors in the CA1 stratum radiatum region during BZ withdrawal. Based on collective findings in this benzodiazepine withdrawal-anxiety model, we propose a functional model illustrating the changes in glutamate receptor populations at excitatory synapses during benzodiazepine withdrawal.
Time Squared: Repeated Measures on Phylogenies

Studies of gene expression profiles in response to external perturbation generate repeated measures data that generally follow nonlinear curves. To explore the evolution of such profiles across a gene family, we introduce phylogenetic repeated measures (PR) models. These models draw strength from 2 forms of correlation in the data. Through gene duplication, the family's evolutionary relatedness induces the first form. The second is the correlation across time points within taxonic units, individual genes in this example. We borrow a Brownian diffusion process along a given phylogenetic tree to account for the relatedness and co-opt a repeated measures framework to model the latter. Through simulation studies, we demonstrate that repeated measures models outperform the previously available approaches that consider the longitudinal observations or their differences as independent and identically distributed by using deviance information criteria as Bayesian model selection tools; PR models that borrow phylogenetic information also perform better than nonphylogenetic repeated measures models when appropriate. We then analyze the evolution of gene expression in the yeast kinase family using splines to estimate nonlinear behavior across 3 perturbation experiments. Again, the PR models outperform previous approaches and afford the prediction of ancestral expression profiles. To demonstrate PR model applicability more generally, we conclude with a short examination of variation in brain development across 4 primate species.
Code generation for a systolic computer

An experiment of a mechanical code generation for a programmable systolic computer is reported. Two-dimensional systolic arrays are automatically reduced to one dimension, and code is generated for the one-dimensional processor array Warp. The technique is demonstrated with two examples: matrix multiplication and LU decomposition.
LXVII. The value of the energy relation in the testing of ferrous metals at varying ranges of stress and at intermediate and high temperatures

(1923). LXVII. The value of the energy relation in the testing of ferrous metals at varying ranges of stress and at intermediate and high temperatures. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science: Vol. 46, No. 274, pp. 609-627.
Monitoring alcohol abuse prevention legislation

Results: The patient population with opioid dependence (excluding heroin) grew 57% between 2007 and 2011, mirroring national trends. Prescription opioid patients, specifically (n=1190), differed from those with alcohol or other drugs as DOC. These individuals were younger in age (M=35, SD=11.97) than cocaine (M=37, SD=9.48) or alcohol patients (M=44, SD=11.75), but older than marijuana patients (M=31, SD=10.12), p< .001. Groups did not differ on the number of co-occurring mental health diagnoses (M=1.40).Opioidpatientshad significantly shorter lengthsof stay (M=25 days, SD=7.85) compared to alcohol patients (M=26, SD=6.40), t(1445) =−3.21,p= .001, andwere less likely to complete treatment (with a 16% atypical discharge rate) compared to the other groups, X2=133.63, p< .001. Among opioid patients, females were overrepresented in atypical discharges. Compared to those whose primary DOC was alcohol, prescription opioid patients had lower self-efficacy at treatment entry, t=−5.588, p< .001. Conclusions: Given the documented role of self-efficacy and treatment completion for favorable outcomes, these data suggest that specific evidence-based interventions are needed to improve chances for positive treatment outcomes. Financial support: Supportedbyprivate donations to theButler Center for Research, Hazelden Foundation.
Dynamin: Membrane Scission Meets Physics

Dynamin hydrolyzes GTP to constrict and sever membranes. Experimental advances bring dynamin into the realm of physics and reveal key roles for membrane tension and bending at the edge of the constriction.
The longitudinal Study of Personality Disorders: History, Design Considerations, and Initial Findings.

The Longitudinal Study of Personality Disorders (LSPD) began in 1990 and it is the first NIMH-funded prospective multiwave longitudinal study of all DSM-defined personality disorders (PDs). The LSPD, now in its 16th year, has focused on several major issues including: (a) the epidemiology of the PDs; (b) the stability of individual differences and mean levels of PD features over time; (c); patterns of individual growth in PD features over time; (d) the development of a neurobehavioral model that links personality and personality disorder; (e) specification of those neurobehavioral systems predicting change in borderline personality disorder; and (f) illumination of simultaneous growth processes in neurobehavioral systems and PD. The LSPD possesses a number of methodological enhancements designed to increase the validity of the longitudinal findings such as a prospective multiwave design, use of a validated structured interview and well-known self-report instrument for Axis II assessments, double measurement of all major constructs under study, use of blinded interviewers for all interview Axis II assessments, and use of a community sample. The history and context in which the LSPD was developed is reviewed, methodological issues related to the study of PDs are discussed, primary LSPD findings to date are summarized, and future directions of the LSPD are introduced.
Purification of the desoxypentose nucleic acid of Hemophilus influenzae having transforming activity.

Abstract The purification of DNA preparations of Hemophilus influenzae , types b and c, endowed with transforming activity is described. The mild procedure makes use of electrophoretic separation of the DNA from contaminating PNA and polysaccharides. The final DNA preparations, free of detectable amounts of these contaminants and of proteins, were active in transformation in concentrations of less than 0.0004 μg. and 0.01 μg. DNA/ml. for types b and c, respectively.
Adult pigs as a source of insulin‐producing tissue for xenotransplantation: Islet separation technology

: Porcine pancreata have been extensively studied as a source of insulin-producing tissue for human transplantation. Substantial technical problems hampered the development of reproducible techniques for islet separation from the adult pig pancreas. Since the introduction of the automated method for human islet transplantation, many steps have been implemented to optimize this method and to adapt it to the requirements of porcine islet isolation. This paper describes the protocols now widely used for adult porcine islet separation and summarizes some of the key variables that influence reproducibility and islet isolation outcome.
Interaction of Tetrahydrocrysene Ketone with Estrogen Receptors α and β Indicates Conformational Differences in the Receptor Subtypes

Abstract Estrogen receptors (ER) α and β bind estradiol (E 2 ) and other estrogenic ligands with different affinities. To measure the rate of E 2 association with ERα and ERβ, we employed tetrahydrocrysene ketone (THCK), a fluorescent ligand that is an agonist with ERα and an antagonist with ERβ. We report that THCK binds E 2 -liganded and unliganded ERα and ERβ, indicating a THCK binding site(s) other than the E 2 binding pocket. THCK fluorescence was greater for ligand-occupied ERβ than ERα, suggesting differences in the microenvironment of the THCK binding site(s). THCK fluorescence was also significantly greater for E 2 -, 4-hydroxytamoxifen-, and tamoxifen aziridine-liganded versus unliganded ER, allowing calculations of E 2 association rate constants ( k a ) of 7.60 ± 0.75 and 5.12 ± 0.30 × 10 5 M −1 s −1 for E 2 -ERα and E 2 -ERβ, respectively. THCK did not affect ERα binding to estrogen response element (ERE) DNA, but decreased ERβ-ERE binding. We conclude that THCK binding site(s) on ERα versus ERβ are different and important for ER function.
Prognostic biomarkers for patients with advanced renal cell carcinoma treated with VEGF-targeted tyrosine kinase inhibitors

Tyrosine kinase inhibitors with activity against vascular endothelial growth factor receptor 2 are now standard treatment for the majority of patients with advanced renal cell carcinoma. The clinical development of these agents followed by their broad clinical utilization has allowed the creation of large databases to facilitate the identification of prognostic biomarkers and development of prognostic models. While several clinical prognostic models have been created, work continues on identifying novel biomarkers which might be used in conjunction with or even in place of these clinical models. In this review, we discuss the progress thus far in improving on current prognostic models and speculate on possible developments in the near future.
Changing trends in keratoplasty.

i t P e s t w n H ISTORICALLY, SAFETY AND EFFICACY HAVE BEEN the most important considerations in evaluating new therapies. With rapidly accelerating healthcare expenditures, increasing attention has been paid to the costs of new procedures. Payers consider cost/benefit ratios in addition to safety and efficacy when making coverage and payment decisions. Those decisions exert increasing control over how rapidly and widely new procedures are adopted. The article by van den Biggelaar on cost-effectiveness of deep anterior lamellar keratoplasty (DALK) versus penetrating keratoplasty (PK) in this issue of the Journal addresses this interplay between clinical and economic factors. Zirm performed the first successful penetrating keratoplasty in 1905. PK eventually became the procedure of choice for corneal blindness and has been predominant for the past half-century. Nevertheless, PK has its problems. Suprachoroidal hemorrhage is rare but devastating. Suturerelated problems are common and can lead to graft failure. Visual rehabilitation is delayed by ocular surface problems and variable refractive error. Long-term astigmatism and ametropia leave some patients unable to attain useful visual function without contact lenses or further surgical intervention. Globe rupture after minor trauma is a permanent risk. Graft failure rates of 14% to 36% at 5 to 10 years and regraft failure rates of 50% or greater can be seen, with immunologic rejection in 15% to 20% of cases contributing, along with nonimmunologic endothelial cell loss, to late graft attrition. Over the past decade, lamellar keratoplasty has begun to supplant PK. Endothelial keratoplasty (EK), by eliminating many of the ocular surface and wound integrity problems associated with PK and by offering faster visual rehabilitation, has become the procedure of choice for patients with endothelial disease. Anterior lamellar kertoplasty (ALK) techniques have evolved to the point that hey now challenge the supremacy of PK for patients with tromal disease. Advantages of DALK include retention of recipient endothelium, eliminating endothelial rejection, less steroid exposure and attendant risks of glaucoma and cataract formation, less distortion of angle anatomy and synechia formation, and an expanded donor pool. DALK results in less long-term endothelial cell loss and higher long-
Flood control failure: San Lorenzo River, California

The San Lorenzo River on the central California coast was the site of a major US Army Corps of Engineers flood control project in 1959. By excavating the channel below its natural grade and constructing levees, the capacity of the river was increased in order to contain approximately the 100 year flood. Production and transport of large volumes of sediment from the river's urbanizing watershed has filled the flood control project with sand and silt. The natural gradient has been re-established, and flood protection has been reduced to containment of perhaps the 30 year flood. In order for the City of Santa Cruz, which is situated on the flood plain, to be protected from future flooding,it must either initiate an expensive annual dredging program, or replan and rebuild the inadequately designed flood control channel. It has become clear, here and elsewhere, that the problem of flooding cannot simply be resolved by engineering. Large flood control projects provide a false sense of security and commonly produce unexpected channel changes.
Characterization of adsorption at kaolinite surfaces by heterogeneous gas—solid chromatography

Abstract Chromatographic techniques have been utilized to determine energy distribution functions for the adsorption of butane and 1-butene on dry and hydrated kaolinite. The energy distributions indicate that the primary adsorption sites occur on the opposing faces of the kaolinite cleavage plane, with little, if any, involvement of broken-bond surfaces. Differences in the butane and butene distributions can be attributed to repulsive interactions between π-electrodes of butene and negatively charged surfaces of the kaolinite cleavage plane. Studies of kaolinite hydrated with small amounts of water demonstrate that water does not form a conventional monolayer, but rather “clusters” around the high energy adsorption sites of the kaolinite surface. Furthermore, the addition of small amounts of water to kaolinite result in a surface significantly different than that of the underlying mineral.
Trafficking and potential assembly patterns of epsilon-containing GABAA receptors.

Incorporation of the e subunit into the GABAA receptor has been suggested to confer unusual, but variable, biophysical and pharmacological characteristics to both recombinant and native receptors. Due to their structural similarity with the γ subunits, e subunits have been assumed to substitute at the single position of the γ subunit in assembled receptors. However, prior work suggests that functional variability in e-containing receptors may reflect alternative sites of incorporation and of not just one, but possibly multiple e subunits in the pentameric receptor complex. Here we present data indicating that increased expression of e, in conjunction with α2 and β3 subunits, results in expression of GABAA receptors with correspondingly altered rectification, deactivation and levels of spontaneous openings, but not increased total current density. We also provide data that the e subunit, like the β3 subunit, can self-export and data from chimeric receptors suggesting that similarities between the assembly domains of the β3 and the e subunits may allow the e subunit to replace the β, as well as the γ, subunit. The substitution of an e for a β, as well as the γ subunit and formation of receptors with alternative patterns of assembly with respect to e incorporation may underlie the observed variability in both biophysical and pharmacological properties noted not only in recombinant, but also in native receptors.
Refinements in mathematics undergraduate students’ reasoning on completed infinite iterative processes

This paper reports a teaching experiment in which two students engaged in tasks that challenged them to describe a final state for a variety of infinite iterative processes. The results from the study indicate that the students used multiple reasoning strategies for addressing these tasks. Refinements in the students’ reasoning occurred as students constructed relationships between the problems they were solving and problems they had solved previously, applying some of the reasoning strategies that they used for one problem to make sense of or solve another problem. We discuss how these findings relate to the existing body of research on infinite iterative processes.
The cognitive psychology of expertise and the domain of interpreting

This article surveys findings from cognitive science research on expertise, with a focus on applications to the domain of simultaneous interpreting, including methods of knowledge elicitation that might be useful in the empirical investigation of proficiency at simultaneous interpreting. Defining features of expertise include its developmental progression, the nature of expert memory organization, and the nature of expert reasoning. I explore ways in which a number of defining criteria might apply to the domain of interpreting. With regard to knowledge elicitation, I explore three knowledge elicitation methods that sample the palette of available methods, specifically, a type of structured interview, a type of task analysis, and a more contrived or laboratory task.
Public/Private Partnerships to Renew the Industrial Landscape

America’s urban areas have experienced a decline over the past two decades. Urban flight has resulted in brownfields, deteriorating infrastructure, environmental pressure on remaining industries, and general economic decline. Federal agencies and community groups have recognized the need for technical solutions to the issues hindering urban redevelopment but lack the scientific and engineering expertise. Argonne National Laboratory has a significant level of technical expertise to apply to the resolution of issues facing these urban communities and industries. Argonne has made a concentrated, coordinated effort to resolve those issues by participating in the Industries of the Future program. An Urban Technology Program was created at Argonne to provide a link between the urban issues and the solutions afforded by the laboratory’s technical resources. Argonne is bringing together a variety of technical expertise to propose, develop, and execute—in partnership with public and private partners—strategies for...
Dynamics of positional enrichment : Theoretical development and application to carbon labeling in Zymomonas mobilis

Positional enrichment analysis has become an important technique for assessing detailed flux distributions and the fates of specific atoms in metabolic pathway systems. The typical approach to positional enrichment analysis is performed by supplying specifically labeled substrate to a cell system, letting the system reach steady state, and measuring where label had arrived and accumulated. The data are then evaluated mathematically with the help of a linear stoichiometric flux distribution model. While this procedure has proven to yield new and valuable insights, it does not address the transient dynamics between providing label and its ultimate steady-state distribution, which is often of great interest to the experimentalist (pulse labeling experiments). We show here that an extension of a recent mathematical method for dynamic labeling analysis is able to shed light on these transitions, thereby revealing insights not obtained with traditional positional enrichment analyses. The method traces the dynamics of one or more carbons through fully regulated metabolic pathways, which, in principle, may be arbitrarily complex. After a brief review of the earlier method and description of the theoretical extension, we illustrate the method with an analysis of the pentose phosphate pathway in Zymomonas mobilis, which has been used for traditional positional enrichment analyses in the past. We show how different labeling schemes result in distinctly different transients, which nevertheless eventually lead to a steady-state labeling profile that coincides exactly with the corresponding profile from traditional analysis. Thus, over the domain of commonality, the proposed method leads to results equivalent to those from state-of-the-art existing methods. However, these steady-state results constitute only a small portion of the insights obtainable with the proposed method. Our method can also be used as an "inverse" technique for elucidating the topology and regulation of pathway systems, if appropriate time series data are available. While such dynamic data are still rather rare, they are now being generated with increasing frequency and we believe it is desirable, and indeed necessary, to accompany this trend with an adequate, rigorous method of analysis.
Conditions for constant growth rate by LPE from a cooling, static solution

It is important to be able to grow crystalline layers at a constant rate in order to have good control over thickness, morphology, and composition. If LPE layers are grown from thin solutions over a relatively small temperature range an essentially constant growth rate can be achieved. The necessary conditions for constant growth rate are: (i) that t/gt⪅0.1, where t is the growth period, and τ the relaxation time associated with an Arrhenius liquidus curve and a steady cooling rate b; τ is given by τ = mC0b, where m is the slope of the liquidus line at the initial temperature and C0 is the intial concentration of the solution, and (ii) that t/τ⪆a2. The parameter a is in the range 3 x 10−2 to 10−1 where a is defined by the equation a=l(DmC0b)12, in which l is the effective linear extent of the solution and D the diffusion coefficient of growth units in it.
Increasing Certification Through Unit-Based Education

Certification has been identified by multiple organizations as an important component and means of elevating the level of nursing care provided to patients and demonstrating to the public that the nursing staff has subspecialty knowledge. Certification may lead to improved patient satisfaction and outcomes as well as increased nurse satisfaction and retention. Despite the known potential benefits associated with certification, institutions struggle to improve certification rates. One possible method to overcome system barriers to certification is the implementation of a unit-based study course to prepare nurses for the Certified Breast Care Nurse (CBCN) examination. Data collected by an author-developed tool as one institution created and executed a unit-based study course suggest that such an approach increased certification rates and improved disease-specific knowledge and confidence among the staff, despite no official data existing on the tool's reliability and validity. Implementation of similar programs may be successful in improving certification at other institutions seeking to raise certification rates.
PERIPHERAL METABOLISM OF THYROXINE IN THYROIDECTOMIZED RATS TREATED WITH CORTISONE.

SummaryThe present study supports the conclusion that cortisone, administered to thyroidectomized, thyroxine-maintained rats does not alter their ability to deiodinate peripheral thyroxine. This is based on the observation that in two separate experiments there was no demonstrable cortisone effect on the level of serum protein-bound protein iodine. In addition, there was no significant difference between control and cortisone-treated animals in regard to either their urinary or fecal 123I excretion as well as no difference in total excretion of radioactivity.
Modeling of Transient Electrical Torques in Solid Iron Rotor Turbogenerators

It has previously been shown that it is necessary to employ a synchronous machine representation with unequal mutual reactances in the direct axis in order to calculate accurately the transient field current. This paper shows that if the stator current is calculated accurately by a synchronous machine model then the instantaneous electromagnetic torque is also accurately predicted. It is further shown that this may be accomplished by a model with two rotor windings in each axis and without representation of unequal mutual reactances. Results are presented to demonstrate the degree of accuracy possible with this model.
Massive carotenoid accumulation in Dunaliella bardawil induced by ultraviolet-A radiation

Abstract The effect of supplementing visible light (i.e., wavelengths in the range 400–700 nm) with ultraviolet-A radiation (320–400 nm) during the growth of Dunaliella bardawil has been investigated. This study focuses on the accumulation of carotenoids. Previous investigations have found that large increases in carotenoids are induced by high-intensity photosynthetically active radiation (PAR) and by various environmental stresses (e.g., high salinity, nutrient deficiencies or low temperature), which significantly reduce growth rates. This study has found that UV-A radiation causes massive increases in carotenoid levels without slowing the growth of D. bardawil in culture. By supplementing various levels of PAR with UV-A radiation (38 μmol m −2 s −1 ) during growth, carotenoid:chlorophyll ratios increase by 80–310%. Per unit protein, UV-A produces a 0–35% decrease in chlorophyll coupled with a doubling of total carotenoids. These large increases in carotenoids are induced by UV-A at all salinities (0.5 to 3.0 M), and at all visible photosynthetic photon flux densities (30–1500 μmol m −2 s −1 ) tested. Induced carotenoid levels are proportional to the intensity of UV-A when growth PAR is held constant. Blue light (200 μmol m −2 s −1 ) is no more effective than white light in carotenoid induction, indicating that this is not a shared blue-light/near-UV effect. UV-B (290–320 nm) is also ineffective in inducing carotenoid increases during growth.
Pfaff's method (II): diverse applications

Abstract In 1797, Pfaff summed a 3F2 hypergeometric series. His result was ignored until Saalschutz rediscovered it in 1890. This paper is devoted to a detailed account of the wide applicability of Pfaff's method.
An expert advisory system for the ISO 9001 quality system

Abstract The ISO 9000 quality management system has been widely accepted and adapted as a national standard by most industrial countries. Despite its high popularity and the urgent demand from customers to implement ISO 9000, some major concerns for those organizations that are seeking registration to ISO 9000 include the expensive cost and the lengthy time to implement. The purpose of this paper is to describe an expert advisory system for ISO 9001 implementation by using an expert system shell called Visual Rules Studio. This expert advisory system integrated the ISO 9001 quality system guidelines and an evaluation approach based on the Malcolm Baldrige National Quality Award (MBNQA) criteria into a knowledge-based expert system. By identifying the critical ISO elements and comparing the company's current quality performance with ISO standards, this advisory system provides assessment results and implementation suggestions to the organization. The advisory system has been validated by a group of quality professionals. The following contains a description of the system and a discussion of the validation results. Limitations of the system and recommendations for future research are also discussed.
Evolution of Earth's Noble Gases: Consequences of Assuming Hydrodynamic Loss Driven by Giant Impact

A simple analytic model of hydrodynamic escape is applied to atmospheric loss from Earth under conditions that are unproven but could plausibly have existed following deposition of thermal energy by a giant Moon-forming impact. Primordial xenon in the primary (pre-impact) atmosphere is readily fractionated to its contemporary nonradiogenic isotopic composition by appropriate selection of parameters in the equations governing the escape process. Subsequent mixing of the fractionated residuals of lighter primordial noble gases surviving in the post-escape atmosphere with solar-composition gases outgassed from the deep planetary interior yields close matches to the present-day abundances and isotopic compositions of atmospheric krypton and argon. Replication of present-day neon composition requires an additional later episode of hydrodynamic H2escape, now powered by extreme-ultraviolet (EUV) solar radiation just intense enough for entrainment and loss of Ne but not of heavier species. Requirements for EUV flux intensity and planetary water inventory are substantially reduced compared to an earlier model of EUV-driven Xe loss from Earth. A noteworthy result of this approach is the close agreement of the noble gas elemental composition characterizing the pre-impact terrestrial atmosphere with that derived for Venus's primary atmosphere from a parallel evolutionary model involving only solar EUV radiation as an energy source. No claim is made that the modeling parameters used here adequately describe the complex and rapidly evolving physical nature of the post-impact terrestrial atmosphere, or that these solutions are unique. But they do suggest a basic unity in primordial noble gas distributions on the two planets, and point to separate mechanisms that could account for divergent evolution to their presently radically different compositional states.
Development and participant assessment of a practical quality improvement educational initiative for surgical residents.

Background As patient-safety and quality efforts spread throughout health care, the need for physician involvement is critical, yet structured training programs during surgical residency are still uncommon. Our objective was to develop an extended quality-improvement curriculum for surgical residents that included formal didactics and structured practical experience. Methods Surgical trainees completed an 8-hour didactic program in quality-improvement methodology at the start of PGY3. Small teams developed practical quality-improvement projects based on needs identified during clinical experience. With the assistance of the hospital's process-improvement team and surgical faculty, residents worked through their selected projects during the following year. Residents were anonymously surveyed after their participation to assess the experience. Results During the first 3 years of the program, 17 residents participated, with 100% survey completion. Seven quality-improvement projects were developed, with 57% completing all DMAIC (Define, Measure, Analyze, Improve, Control) phases. Initial projects involved issues of clinical efficiency and later projects increasingly focused on clinical care questions. Residents found the experience educationally important (65%) and believed they were well equipped to lead similar initiatives in the future (70%). Based on feedback, the timeline was expanded from 12 to 24 months and changed to start in PGY2. Conclusions Developing an extended curriculum using both didactic sessions and applied projects to teach residents the theory and implementation of quality improvement is possible and effective. It addresses the ACGME competencies of practice-based improvement and learning and systems-based practice. Our iterative experience during the past 3 years can serve as a guide for other programs.
Truth in Communication

In October, 1964, the Journal of Business Communication published an article by Professor Bernard Sarachek, of Rutgers University, entitled “An Honest Appraisal of Honesty in Communication” (pp. 11–17). The thesis of this article follows: Simply stated, the successful communicator is one who knows exactly how much of his information and intentions to communicate to others. He knows the extent to which he must distort or color his information in order to induce others to accept the attitudes he desires. For the successful communicator, ethical communication and effective communication need not be treated as synonymous terms, (pp. 11–12)
Low-complexity hierarchical lapped transform for lossy-to-lossless image coding in JPEG XR / HD Photo

JPEG XR is a draft international standard undergoing standardization within the JPEG committee, based on a Microsoft technology known as HD Photo. One of the key innovations in the draft JPEG XR standard is its integer-reversible hierarchical lapped transform. The transform can provide both bit-exact lossless and lossy compression in the same signal flow path. The transform requires only a small memory footprint while providing the compression benefits of a larger block transform. The hierarchical nature of the transform naturally provides three levels of multi-resolution signal representation. Its small dynamic range expansion, use of only integer arithmetic and its amenability to parallelized implementation lead to reduced computational complexity. This paper provides an overview of the key ideas behind the transform design in JPEG XR, and describes how the transform is constructed from simple building blocks.
Nutrient Restriction and Radiation Therapy for Cancer Treatment: When Less Is More

Calorie restriction (CR), or a diet modification aiming to reduce the total intake of calories by 20%-40%, has been shown to increase longevity across multiple species. Recently, there has been growing interest in investigating the potential role of CR as a treatment intervention for age-related diseases, such as cancer, because an increasing body of literature has demonstrated a metabolic component to both carcinogenesis and tumor progression. In fact, many of the molecular pathways that are altered with CR are also known to be altered in cancer. Therefore, manipulation of these pathways using CR can render cancer cells, and most notably breast cancer cells, more susceptible to standard cytotoxic treatment with radiation and chemotherapy. In this review article we demonstrate the laboratory and clinical evidence that exists for CR and show compelling evidence through the molecular pathways CR induces about how it may be used as a treatment in tandem with radiation therapy to improve our rates of disease control.
Use of satellite data to assess the impacts of irrigation withdrawals on Upper Klamath Lake, Oregon

Abstract. Competition for scarce water resources in the Upper Klamath River Basin, Oregon has generated conflict among its stakeholders, as demonstrated by recent regulations on withdrawals from Upper Klamath Lake. Information on agricultural water usage can help assess the hydrologic impacts of irrigation and support operational decisions. This paper presents an experimental satellite-based evapotranspiration estimation system that is combined with the Variable Inflitration Capacity (VIC) hydrological model to estimate irrigation consumption, which is then used to assess the effects of irrigated agriculture on lake storage volumes and water levels. The hydrological model is calibrated with streamflow observations and used to estimate unmeasured lake inflows and guide water budget calculations. When combined with the VIC model, the satellite-based evapotranspiration estimation system shows that irrigation caused a decline of 0.3 m in average annual water levels and 0.5 m in mean October water levels, and an increase of 0.5 m in annual water level ranges at the lake from 2001 to 2005. The results demonstrate the potential of satellite data for agricultural water resource management at the regional scale.
Ins2 Deficiency Augments Spontaneous HLA-A*0201–Restricted T Cell Responses to Insulin

Type 1 diabetes results from the autoimmune destruction of insulin-producing beta cells by T cells specific for beta cell Ags, including insulin. In humans, the non-MHC locus conferring the strongest disease susceptibility is the insulin gene, and alleles yielding lower thymic insulin expression are predisposing. We sought to incorporate this characteristic into an HLA-transgenic model of the disease and to determine the influence of reduced thymic insulin expression on CD8+ T cell responses to preproinsulin. We examined NOD.Ins2(-/-) mice, which do not express insulin in the thymus and show accelerated disease, to determine whether they exhibit quantitative or qualitative differences in CD8+ T cell responses to preproinsulin. We also generated NOD.Ins2(-/-) mice expressing type 1 diabetes-associated HLA-A*0201 (designated NOD.beta2m(-/-).HHD.Ins2(-/-)) in an effort to obtain an improved humanized disease model. We found that CD8+ T cell reactivity to certain insulin peptides was more readily detected in NOD.Ins2(-/-) mice than in NOD mice. Furthermore, the proportion of insulin-reactive CD8+ T cells infiltrating the islets of NOD.Ins2(-/-) mice was increased. NOD.beta2m(-/-).HHD.Ins2(-/-) mice exhibited rapid onset of disease and had an increased proportion of HLA-A*0201-restricted insulin-reactive T cells, including those targeting the clinically relevant epitope Ins B10-18. Our results suggest that insulin alleles that predispose to type 1 diabetes in humans do so, at least in part, by facilitating CD8+ T cell responses to the protein. We propose the NOD.beta2m(-/-).HHD.Ins2(-/-) strain as an improved humanized disease model, in particular for studies seeking to develop therapeutic strategies targeting insulin-specific T cells.
Effect of ultraviolet light on dissolved nitrogen transformations in coastal lagoon water

The effect of ultraviolet radiation on the production of inorganic nitrogen, urea, and amino acids from aquatic dissolved organic matter (DOM) was investigated for waters from Hog Island Bay, a coastal lagoon in Virginia. Waters representing distinct sources of DOM to the lagoon were subjected to UV light mimicking the natural solar spectrum. Dissolved organic nitrogen concentrations did not change measurably during the 36-h incubation, while calculated dissolved organic carbon concentrations dropped by up to 17%, resulting in decreases in estimated C/N for some samples. Nitrate and urea levels were not consistently altered in the light, while ammonium photoproduction rates of up to 0.032 mmol N L 21 h 21 were observed. Changes in dissolved free amino acids were measured in a groundwater sample obtained from a shoreline seep, and this sample exhibited photoproduction of glycine and alanine at rates of 0.8‐1.1 nmol N L 21 h 21 . The rates of ammonium and amino acid formation, when scaled up to estimate photoproduction in the lagoon system, appeared to be minor relative to other sources to and fluxes within the system.
Changing course of diabetic nephropathy in the Pima Indians

Pima Indians from the Gila River Indian Community in Arizona have a high incidence rate of type 2 diabetes, and kidney disease attributable to diabetes is a major cause of morbidity and mortality in this population. Since 1965, each member of the population at least 5 years of age is invited to participate in a research examination every other year. During the past 43 years, the overall incidence of diabetes in the Pima Indians has not changed, but the incidence of diabetes among those less than 15 years of age has increased nearly 6-fold, as an increasing prevalence and degree of obesity in the youth have shifted the onset of diabetes to younger ages. The rising frequency of diabetes in the youth has led, in turn, to the emergence in mid-life of the major complications of diabetes, including kidney disease. On the other hand, the introduction and widespread use of medicines to control blood pressure, reduce hyperglycemia, and block the renin-angiotensin system (RAS) have lead to improvements in the average blood pressure and glycosylated hemoglobin levels in the diabetic population. These countervailing forces have influenced the course of diabetic nephropathy in a generally favorable direction in the past few years, as evidenced by the decline in the overall incidence of end-stage kidney disease since 1990. A continued increase in the incidence of type 2 diabetes in youth, however, threatens to reverse this trend.
Targeting the vascular endothelial growth factor pathway in the treatment of multiple myeloma.

Multiple myeloma is a clonal plasma cell malignancy within the bone marrow associated with bone loss, renal disease and immunodeficiency. Despite new insights into the pathogenesis of multiple myeloma and novel targeted therapies, the median survival remains 3–5 years. It is now well established that the intimate relation between the tumor cells and components of the microenvironment plays a key role in multiple myeloma pathogenesis. Specifically, tumor cells impact the bone marrow and thereby cause immune suppression and lytic bone lesions; conversely, components of the bone marrow provide signals that influence the behavior of multiple myeloma cells, including tumor cell growth, survival, migration and drug resistance. Important contributing effectors are tumor cell–stroma cell and cell–extracellular matrix contacts, the bone marrow vasculature, and a variety of cytokines and growth factors in the bone marrow milieu.
Motivating Factors in Futile Clinical Interventions

With modern medical technology, it is now possible to sustain life for prolonged periods in critically ill patients, even when there is no reasonable hope of improvement or achieving the goals of therapy. Such futile and medically inappropriate interventions may violate both the ethical and medical precepts generally accepted by patients, families, and physicians. In this study, we sought to determine who was primarily responsible for such interventions, the nature of their motivation, and the role of a timely bioethical consultation. In a retrospective review, we identified 100 patients of 331 bioethical consultations who had futile or medically inappropriate therapy. The average age of patients was 73.5 6 32 years (mean 6 2 SD) with 57% being male. Fifty-seven percent of the patients were admitted to the hospital with a degenerative disorder, 21% with an inflammatory disorder, and 16% with a neoplastic disorder. The family was responsible for futile treatment in 62% of cases, the physician in 37% of cases, and a conservator in one case. Unreasonable expectation for improvement was the most common underlying factor. Family dissent was involved in 7 of 62 cases motivated by family, but never when physicians were primarily responsible. Liability issues motivated physicians in 12 of 37 cases where they were responsible but in only 1 of 62 cases when the family was (x 2 5 degrees of freedom 5 26.7, p < 0.001). When the bioethics consultation resulted in cessation of the therapy, patients died in a median of 2 days as opposed to 16 days if therapy continued (p < 0.001). (CHEST 2001; 119:1944 ‐1947)
Novel mouse hemostasis model for real-time determination of bleeding time and hemostatic plug composition.

Summary Introduction Hemostasis is a rapid response by the body to stop bleeding at sites of vessel injury. Both platelets and fibrin are important for the formation of a hemostatic plug. Mice have been used to uncover the molecular mechanisms that regulate the activation of platelets and coagulation under physiologic conditions. However, measurements of hemostasis in mice are quite variable, and current methods do not quantify platelet adhesion or fibrin formation at the site of injury. Methods We describe a novel hemostasis model that uses intravital fluorescence microscopy to quantify platelet adhesion, fibrin formation and time to hemostatic plug formation in real time. Repeated vessel injuries of ~ 50–100 μm in diameter were induced with laser ablation technology in the saphenous vein of mice. Results Hemostasis in this model was strongly impaired in mice deficient in glycoprotein Ibα or talin-1, which are important regulators of platelet adhesiveness. In contrast, the time to hemostatic plug formation was only minimally affected in mice deficient in the extrinsic tissue factor (TFlow) or the intrinsic factor IX coagulation pathways, even though platelet adhesion was significantly reduced. A partial reduction in platelet adhesiveness obtained with clopidogrel led to instability within the hemostatic plug, especially when combined with impaired coagulation in TFlow mice. Conclusions In summary, we present a novel, highly sensitive method to quantify hemostatic plug formation in mice. On the basis of its sensitivity to platelet adhesion defects and its real-time imaging capability, we propose this model as an ideal tool with which to study the efficacy and safety of antiplatelet agents.
Computational experience with the batch means method

This article discusses implementation issues for the LBATCH and ABATCH batch means procedures of Fishman and Yarberry (1997). Theses procedures dynamically increase the batch size and the number of contiguous batches based on the outcome of a hypothesis test for independence among the batch means. We show that both procedures require O(n) time and O(log,n) space, where n is the desired sample size. Although like complexities are known for static fixed batch size algorithms, the dynamic setting of the LBATCH and ABATCH rules offers an important additional advantage not present in the static approach. As the analysis evolves with increasing sample path length, it allows a user to assess how well the estimated variance of the sample mean stabilizes. This assessment is essential to gauge the quality of the confidence interval for the sample mean. The LABATCH implementation (described in Fishman 1996 and Fishman and Yarberry 1997) of the LBATCH and ABATCH rules is the only computer package that automatically generates the data for this assessment.
Effect of various acids at different concentrations on the pinacol rearrangement

The acid catalyzed pinacol–pinacolone rearrangement has been well studied for a long time 1 and has served as a standard topic in most undergraduate organic textbooks. With benzopinacol as the diol, tetraphenylethylene oxide was also produced 2 in addition to the expected benzopinacolone. Several non-dehydrative pinacol rearrangements with various Lewis acids have also been reported. 3 More recently, similar rearrangements were observed in the presence of aminium salts. 4 A theoretical study of the mechanism that involves both stepwise and concerted reaction paths has been described by Nakamura and Osamura. 5 Although, the classical pinacol to pinacolone rearrangement is well documented, we were intrigued by some reports 1j that under certain acidic conditions, 2,3-dimethyl-1,3-butadiene becomes the major product in the reaction. This suggests a shift in the mechanistic pathway (Scheme 1) leading to the preferred formation of 2. In order to understand the competing reaction pathways, we evaluated the effect of changing the concentration of various acids as well as the effect of added conjugate base. Our results indicate that although the 1,2-migration is the preferred pathway, the alternative route also competes leading to products 2 and 3 (Scheme 1). The change in the ratio of rearrangement to elimination products described in this work is in agreement with the results obtained in the pinacol–pinacolone rearrangement of 2,3-di-(3-pyridyl)-2,3-butanediol in sulfuric acid and the effect of added water. 6