cssi/SciSciGPT-SciSciNet huggingface dataset:
Juvenile diabetes: Impact on the child and family

Abstract The work of a child psychiatrist and a social worker with a group of adolescent juvenile diabetics is described. The conceptual framework that emerged from this experience draws on developmental and psychodynamic theory that may be applied to other chronic disease patients. The authors provide recommendations for the practical application of the model for pediatricians and describe the acceptance of the diagnosis as akin to the mourning process.
Flavors in Poultry Rations

Abstract The recent work of Kare (Kare et al., 1957; Kare and Medway, 1959; Lindenmaier and Kare, 1959) which demonstrated the taste perception of the chicken has been interpreted to imply that the flavoring of feeds might result in superior feed utilization and weight gains (Deyoe et al., 1962). The latter workers demonstrated that certain flavors were acceptable to the chicken but that neither weight gain nor efficiency of feed utilization was influenced, presumably because the flavors were included in the water rather than in the feed. In view of the continuing interest in the subject of flavoring we have decided to report on a series of experiments with various flavoring compounds added to the feed which were carried out several years ago at the University of Illinois. Experiment 1 was carried out with 17 different flavoring compounds which are itemized in Table 1. The 4-week weights and feed efficiency values …
Proton Irradiation Effects on the Performance of III-V-Based, Unipolar Barrier Infrared Detectors

An examination of the collective results from recent experiments quantifying the performance degradation rates of III-V-based, unipolar barrier infrared detectors with various designs and materials, cutoff wavelengths and operating conditions due to 63 MeV proton irradiation is presented. Empirical relationships were established between the radiation damage factors for dark current density, lateral optical collection length, and quantum efficiency and the inverse product of the detectors’ cutoff wavelength and operating temperature. Fitting the dark current density damage factor’s empirical relationship reflected these detectors’ tendency to remain diffusion-limited during irradiation, which was previously established using Arrhenius-analysis of the post-irradiation, temperature-dependent dark current measurements on each. Collectively, the results affirmed the performance degradation stemmed from a reduction of the minority carrier recombination lifetime via generation of additional defects by proton-induced displacement damage. For comparing detector’s radiation-tolerance, the results indicated that damage factors alone were not ideal, but their empirical relationships would serve as heuristics in this role.
Synthesis of porphyrins bearing 1-4 hydroxymethyl groups and other one-carbon oxygenic substituents in distinct patterns

Abstract Porphyrins that bear one-carbon oxygenic substituents (hydroxymethyl, formyl, ester) directly attached to the macrocycle afford a compact architecture of utility for diverse applications. Routes to 9 porphyrins bearing such groups in distinct architectures (A4-, trans-A2-, trans-A2B2-, trans-AB-, and trans-AB2C-porphyrins) have been explored (A=hydroxymethyl), including porphyrins bearing two one-carbon units in different oxidation states (hydroxymethyl/ester, formyl/ester). The hydroxymethyl group was introduced via TBDMS-protected dipyrromethane precursors.
Demonstration of phosphoryl group transfer indicates that the ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) exhibits adenylate kinase activity.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane-spanning adenosine 5′-triphosphate (ATP)-binding cassette (ABC) transporter. ABC transporters and other nuclear and cytoplasmic ABC proteins have ATPase activity that is coupled to their biological function. Recent studies with CFTR and two nonmembrane-bound ABC proteins, the DNA repair enzyme Rad50 and a structural maintenance of chromosome (SMC) protein, challenge the model that the function of all ABC proteins depends solely on their associated ATPase activity. Patch clamp studies indicated that in the presence of physiologically relevant concentrations of adenosine 5′-monophosphate (AMP), CFTR Cl− channel function is coupled to adenylate kinase activity (ATP+AMP ⇆ 2 ADP). Work with Rad50 and SMC showed that these enzymes catalyze both ATPase and adenylate kinase reactions. However, despite the supportive electrophysiological results with CFTR, there are no biochemical data demonstrating intrinsic adenylate kinase activity of a membrane-bound ABC transporter. We developed a biochemical assay for adenylate kinase activity, in which the radioactive γ-phosphate of a nucleotide triphosphate could transfer to a photoactivatable AMP analog. UV irradiation could then trap the 32P on the adenylate kinase. With this assay, we discovered phosphoryl group transfer that labeled CFTR, thereby demonstrating its adenylate kinase activity. Our results also suggested that the interaction of nucleotide triphosphate with CFTR at ATP-binding site 2 is required for adenylate kinase activity. These biochemical data complement earlier biophysical studies of CFTR and indicate that the ABC transporter CFTR can function as an adenylate kinase.
The role of scaffold proteins in MEK/ERK signalling

Signal transduction networks allow cells to recognize and respond to changes in the extracellular environment. All eukaryotic cells have MAPK (mitogen-activated protein kinase) pathways that participate in diverse cellular functions, including differentiation, survival, transformation and movement. Five distinct groups of MAPKs have been characterized in mammals, the most extensively studied of which is the Ras/Raf/MEK [MAPK/ERK (extracellular-signal-regulated kinase) kinase]/ERK cascade. Numerous stimuli, including growth factors and phorbol esters, activate MEK/ERK signalling. How disparate extracellular signals are translated by MEK/ERK into different cellular functions remains obscure. Originally identified in yeast, scaffold proteins are now recognized to contribute to the specificity of MEK/ERK pathways in mammalian cells. These scaffolds include KSR (kinase suppressor of Ras), β-arrestin, MEK partner-1, Sef and IQGAP1. Scaffolds organize multiprotein signalling complexes. This targets MEK/ERK to specific substrates and facilitates communication with other pathways, thereby mediating diverse functions. The adaptor proteins regulate the kinetics, amplitude and localization of MEK/ERK signalling, providing an efficient mechanism that enables an individual extracellular stimulus to promote a specific biological response. Abbreviations: EGF, epidermal growth factor; ERK, extracellular-signal-regulated kinase; IMP, impedes mitogenic signal propagation; JNK, c-Jun N-terminal kinase; KSR, kinase suppressor of Ras; MAPK, mitogen-activated protein kinase; MEK, MAPKK, MAPK/ERK kinase; MEKK, MAPKKK, MAPK kinase kinase; MP1, MEK partner-1; NGF, nerve growth factor; SOS, son of sevenless
High temperature interaction behavior at liquid metal-ceramic interfaces

Liquid metal/ceramic interaction experiments were undertaken at elevated temperatures with the purpose of developing reusable crucibles for melting reactive metals. The metals used in this work included zirconium (Zr), Zr-8 wt.% stainless steel, and stainless steel containing 15 wt.% Zr. The ceramic substrates include yttria, Zr carbide, and hafnium (Hf) carbide. The metal-ceramic samples were placed on top of a tungsten (W) dish. These experiments were conducted with the temperature increasing at a controlled rate until reaching set points above 2000 °C; the systems were held at the peak temperature for about five min and then cooled. The atmosphere in the furnace was argon (Ar). An outside video recording system was used to monitor the changes on heating up and cooling down. All samples underwent a post-test metallurgical examination. Pure Zr was found to react with yttria, resulting in oxygen (O) evolution at the liquid metal-ceramic interface. In addition, dissolved O was observed in the as-cooled Zr metal. Yttrium (Y) was also present in the Zr metal, but it had segregated to the grain boundaries on cooling. Despite the normal expectations for reactive wetting, no transition interface was developed, but the Zr metal was tightly bound to yttria ceramic. Similar reactions occurred between the yttria and the Zr-stainless steel alloys. Two other ceramic samples were Zr carbide and Hf carbide; both carbide substrates were wetted readily by the molten Zr, which flowed easily to the sides of the substrates. The molten Zr caused a very limited dissolution of the Zr carbide, and it reacted more strongly with the Hf carbide. These reactive wetting results are relevant to the design of interfaces and the development of reactive filler metals for the fabrication of high temperature components through metal-ceramic joining. Parameters that have a marked impact on this interface reaction include the thermodynamic stability of the substrate, the properties of the modified interface, the temperature-dependent solubility limits of the liquids and solid phases, and the high-temperature stoichiometry of the ceramic.
Magnetic domain walls in constrained geometries

Magnetic domain walls have been studied in micrometer-sized ${\mathrm{Fe}}_{20}{\mathrm{Ni}}_{80}$ elements containing geometrical constrictions by spin-polarized scanning electron microscopy and numerical simulations. By controlling the constriction dimensions, the wall width can be tailored and the wall type modified. In particular, the width of a ${180}^{\ifmmode^\circ\else\textdegree\fi{}}$ N\'eel wall can be strongly reduced or increased by the constriction geometry compared with the wall in unconstrained systems.
Forced oscillations and suppression of oscillations in nonlinear sampled-data systems

In this paper, a procedure is developed to investigate and predict the properties of certain types of forced oscillations in a class of nonlinear sampled-data control systems. Use is made of the discrete describing function, and the results are checked on the IBM 7094 digital computer. A sinusoidal input signal with variable amplitude and phase is applied to a relay-type sampled-data control system. It is shown that the input signal has the effect of changing the shape of the critical regions of the negative-inverse of the discrete describing function. The amplitude, phase, and frequency of the forced oscillation can be computed from the intersection between the critical region and frequency loci of the linear portion of the system. Proper selections of amplitude, phases and frequency of the forcing sinusoidal signal permit the elimination and suppression of certain types of sustained oscillations in the system.
MRI of transgene expression: correlation to therapeutic gene expression.

Magnetic resonance imaging (MRI) can provide highresolution 3D maps of structural and functional information, yet its use of mapping in vivo gene expression has only recently been explored. A potential application for this technology is to noninvasively image transgene expression. The current study explores the latter using a nonregulatable internalizing engineered transferrin receptor (ETR) whose expression can be probed for with a superparamagnetic Tf-CLIO probe. Using an HSV-based amplicon vector system for transgene delivery, we demonstrate that: 1) ETR is a sensitive MR marker gene; 2) several transgenes can be efficiently expressed from a single amplicon; 3) expression of each transgene results in functional gene product; and 4) ETR gene expression correlates with expression of therapeutic genes when the latter are contained within the same amplicon. These data, taken together, suggest that MRI of ETR expression can serve as a surrogate for measuring therapeutic transgene expression.
A low-cost technique to cryo-protect and freeze rodent brains, precisely aligned to stereotaxic coordinates for whole-brain cryosectioning

A major challenge in the histological sectioning of brain tissue is achieving accurate alignment in the standard coronal, horizontal, or sagittal planes. Correct alignment is desirable for ease of subsequent analysis and is a prerequisite for computational registration and algorithm-based quantification of experimental data. We have developed a simple and low-cost technique for whole-brain cryosectioning of rodent brains that reliably results in a precise alignment of stereotactic coordinates. The system utilises a 3-D printed model of a mouse brain to create a tailored cavity that is used to align and support the brain during freezing. The alignment of the frozen block is achieved in relation to the fixed edge of the mold. The system also allows for two brains to be frozen and sectioned simultaneously. System components, procedural steps, and examples of the end results are presented.
Mass-storage management for distributed image/video archives

The realization of image/video database requires a specific design for both database structures and mass storage management. This issue has addressed the project of the digital image/video database system that has been designed at IBM SEMEA Scientific & Technical Solution Center. Proper database structures have been defined to catalog image/video coding technique with the related parameters, and the description of image/video contents. User workstations and servers are distributed along a local area network. Image/video files are not managed directly by the DBMS server. Because of their wide size, they are stored outside the database on network devices. The database contains the pointers to the image/video files and the description of the storage devices. The system can use different kinds of storage media, organized in a hierarchical structure. Three levels of functions are available to manage the storage resources. The functions of the lower level provide media management. They allow it to catalog devices and to modify device status and device network location. The medium level manages image/video files on a physical basis. It manages file migration between high capacity media and low access time media. The functions of the upper level work on image/video file on a logical basis, as they archive, move and copy image/video data selected by user defined queries. These functions are used to support the implementation of a storage management strategy. The database information about characteristics of both storage devices and coding techniques are used by the third level functions to fit delivery/visualization requirements and to reduce archiving costs.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
The activity of the lithium—sodium countertransport system in erythrocytes in depression and mania

Abstract The activity of the lithium-sodium countertransport system in erythrocytes was estimated in 16 control subjects and 28 patients suffering from affective disorders (11 bipolar, 17 unipolar) during depression, mania and remission. In all the patients studied, mean estimates of countertransport were significantly lower during an episode than after remission, with low values occuring more frequently in mania than in depression in bipolar patients. The mean values in patients with affective disorders but who were in remission remained lower than those of control subjects. Lowest values occured more frequently in patients with bipolar than in those with unipolar illness. The possible physiological significance of reductions in the activity of the lithium-sodium countertransport mechanism in red cells was discussed.
SHORT-TERM SAFETY AND EFFICACY OF AN APPETITE SUPPRESSANT IN CHILDHOOD OBESITY • 410

Child-onset obesity is a serious individual and public health problem. Existing therapy using diet, exercise, and behavior modification (DEBM) has had limited success, particularly for low-income families with limited resources and access. Adult studies show appetite suppressant medication (ASM) is safe and effective, but there are no adequate studies in children. We performed a randomized, double-blind, placebo-controlled, crossover study with good statistical power, to see if ASM (phentermine 15 mg orally once every morning before breakfast) with DEBM is safe and effective in children ages 7-12 with body mass index (BMI) > 95th percentile for age and sex. 35 patients have completed the study. Each received weekly extensive DEBM beginning at least 2 weeks before ASM/placebo and continuing throughout the study. Group 1 was treated with ASM for 2 months then placebo for 2 months, Group 2 was treated with placebo then crossed over to ASM. The BMI change was-1.24 kg/M2 for Group 1 and -0.23 for Group 2 (P < 0.0008, t-test) during the first 2 months before crossover. After crossover, the change in BMI was +0.91 for Group 1 and -0.69 for Group 2 (P < 0.0004). BMI changes were also significant controlling for age, sex, and height (i.e., after conversion to z-scores). Extensive monitoring of mood, cognition, and school performance using the Teacher and Parent Child Behavior Checklist, Profile of Mood States, and Continuous Performance Test, pre-, during, and after ASM showed no adverse effects. Height velocity was unaffected, and troublesome side-effects were minimal. This study shows that ASM is safe and effective short-term, and appears to be more potent than DEBM. Successful completion of this short-term study clears the way for long-term trials similar to those completed in adults showing safety and efficacy for up to 4 years of continuous use.
DOI-based reconstruction algorithms for a compact breast PET scanner

Purpose: The authors discuss the design and evaluate the performance of combined event estimation and image reconstruction algorithms designed for a proposed high-resolution rectangular breast PETscanner (PETX). The PETX scanner will be capable of measuring the depth of interaction by utilizing detector modules composed of depth-of-interaction microcrystal element (dMiCE) crystal pairs. This design allows a unique combination of event estimation and fast projection methods. Methods: The authors implemented a Monte Carlo simulator to model the PETX system using only true coincident events. The performance of the dMiCE crystal pairs was determined experimentally over a range of depths of interaction. This distribution was used to simulate the noisy dMiCE detector signals and to estimate the line of response for each decay. Three different statistical methods were implemented to determine photon event positioning. Images were reconstructed from these line of response estimators with the exact planogram frequency distance rebinning algorithm, which is an exact analytical reconstruction algorithm for planar systems. Reconstructed images were analyzed with contrast, noise, and spatial resolution metrics. Results: The authors’ simulations demonstrate the ability for the PETX system to produce quantitatively accurate images from true coincident events with a contrast recovery coefficient of greater than 0.8 for 5 mm spheres at the axial center of the scanner and a spatial resolution (FWHM) of 3 mm throughout most of the imaging field of view. Conclusions: The authors’ proposed positioning and reconstruction algorithms for the PETX system show the potential for creating high-quality, high-resolution, and quantitatively accurate images within a clinically feasible reconstruction time.
Role of HuD and other RNA‐binding proteins in neural development and plasticity

Transcription factors have traditionally been viewed as the main determinants of gene expression. Yet, in recent years it has become apparent that RNA-binding proteins also play a critical role in determining the levels of expression of a large number of genes. Once mRNAs are transcribed, RNA-binding proteins can control all subsequent steps in their function, from alternative splicing and translation to mRNA transport and stability. In the nervous system, a large number of genes are regulated post-transcriptionally via the interaction of their mRNAs with specific RNA-binding proteins. This type of regulation is particularly important in the control of the temporal and spatial pattern of gene expression during neural development. This review will discuss the function of the embryonic lethal abnormal vision (ELAV)/Hu family of nervous system-specific RNA-binding proteins, with a special emphasis on HuD, a member of this family that controls GAP-43 mRNA stability and expression. In addition, we will present recent findings on other neural RNA-binding proteins: the ribonucleoprotein K homology (KH)-domain proteins, Fragile X mental retardation protein (FMRP), quakinguiable protein (QKI), and Nova-1. Together with the ELAV/Hu family, these proteins are essential for proper neural development and in some cases for plasticity in the mature brain. The biological significance of these proteins is evident not only by their evolutionary conservation but also by the magnitude of problems arising from autoimmune reactions against them or from mutations affecting their expression or function.
Stress-induced effects, which inhibit host defenses, alter leukocyte trafficking.

Acute cold restraint stress (ACRS) has been reported to suppress host defenses against Listeria monocytogenes, and this suppression was mediated by beta1-adrenoceptors (β1-ARs). Although ACRS appears to inhibit mainly early innate immune defenses, interference with leukocyte chemotaxis and the involvement of β1-AR (or β2-AR) signaling had not been assessed. Thus, the link between sympathetic nerve stimulation, release of neurotransmitters, and changes in blood leukocyte profiles, including oxidative changes, following ACRS was evaluated. The numbers of leukocyte subsets in the blood were differentially affected by β1-ARs and β2-ARs following ACRS; CD3+ (CD4 and CD8) T-cells were shown to be decreased following ACRS, and the T cell lymphopenia was mediated mainly through a β2-AR mechanism, while the decrease in CD19+ B-cells was influenced through both β1- and β2-ARs, as assessed by pharmacological and genetic manipulations. In contrast to the ACRS-induced loss of circulating lymphocytes, the number of circulating neutrophils was increased (i.e., neutrophilia), and this neutrophilia was mediated through β1-ARs. The increase in circulating neutrophils was not due to an increase in serum chemokines promoting neutrophil emigration from the bone marrow; rather it was due to neutrophil release from the bone marrow through activation of a β1-AR pathway. There was no loss of glutathione in any of the leukocyte subsets suggesting that there was minimal oxidative stress; however, there was early production of nitric oxide and generation of some protein radicals. Premature egress of neutrophils from bone marrow is suggested to be due to norepinephrine induction of nitric oxide, which affects the early release of neutrophils from bone marrow and lessens host defenses.
Stability of adolescent body mass index during three years of follow-up.

Objective A 4-year longitudinal study was conducted to determine the prevalence of overweight, detect shifts in body mass index (BMI) distribution, and determine which adolescents were at risk for pathologic weight gain. Study design BMI was analyzed in 1746 adolescents in years 1 (2001-2002) through 4 (2004-2005) of a school-based study. Changes in BMI-Z according to baseline BMI category were examined with general linear modeling. Results In year 1, the prevalence of at risk for overweight (BMI = 85th-95th percentile) and overweight (BMI ≥ 95th percentile) was 19.1% and 18.1%, respectively. Between years 1 and 4, the cohort exhibited no increase in the prevalence of at risk for overweight (19.1% versus 17.2%) or overweight (18.2% versus 18.8%; P > .5). The mean BMI Z-score (BMI-Z) for the cohort was identical in years 1 and 4 (0.66 ± 1.0 Z-score units). Although the overall cohort exhibited stability in BMI-Z, individuals at the lowest categories of BMI-Z (year 1 BMI Z-score P P for difference Conclusion The study cohort exhibited stability in adiposity during 3 years of follow-up. However, lean adolescents, particularly girls, experienced significant increases in BMI-Z, beyond that expected for age- and sex-related growth.
A Multicenter, First-in-Pediatrics, Phase 1, Pharmacokinetic and Pharmacodynamic Study of Ridaforolimus in Patients with Refractory Solid Tumors

Purpose: Ridaforolimus (MK-8669, AP23573) is a potent and selective mammalian target of rapamycin (mTOR) inhibitor. Preclinically, ridaforolimus displays antiproliferative activity against a variety of human tumors in vitro and tumor xenograft models in vivo , with additive or synergistic activity when combined with other anticancer agents. Antitumor activity has been confirmed in adults. This phase I study determined the safety, pharmacological, biologic, and toxicity profiles of ridaforolimus in pediatric patients with refractory malignancies. Experimental Design: Eligible children ages 1 to 18 years with advanced solid tumors were enrolled in a 3 + 3 dose escalation design, to determine the safety, tolerability, and maximum tolerated dose (MTD)/dose-limiting toxicity (DLT) of ridaforolimus. Toxicities, pharmacokinetics, and pharmacodynamics were characterized. Results: Fifteen patients were treated. No DLT was observed at any dose level tested; therefore, an MTD was not identified. Most adverse events were mild to moderate; the most common grades 3 and 4 adverse events were hematologic, including thrombocytopenia and anemia. Nonhematologic adverse events were mostly electrolyte disturbances. The observed pharmacokinetic profile of ridaforolimus in children was consistent with that previously showed in adults. Pharmacodynamic confirms that the dose range tested has pharmacological/pharmacodynamic activity. Forty percent of patients achieved stable disease including four of six with central nervous system tumors and two of eight with sarcomas. Conclusions: This first-in-pediatrics study shows that the second-generation mTOR inhibitor ridaforolimus is well tolerated in heavily pretreated children with refractory solid tumors. No DLTs were observed over the dose range tested. Ridaforolimus may represent a therapeutic option for use in pediatric malignancies. Clin Cancer Res; 19(13); 3649–58. ©2013 AACR .
Wavelength Conversion of Optically Labeled 112-Gb/s Polarization-Multiplexed RZ-QPSK Packets

Wavelength conversion (WC) based on four-wave mixing for polarization-multiplexed (PolMux) signals in an optical switching network with digital coherent detection is experimentally demonstrated for the first time. By employing a dual-pump scheme, polarization-insensitive and channel-preserving WC of optically labeled packets has been realized. The optical packet includes one payload with PolMUX return-to-zero quadrature phase-shift keying signal at 112 Gb/s and one optical label with 2.5-Gb/s on-off keying signal. The bit-error-rate performances for both payload and label are evaluated after WC in this optical network. The converted payload has less than a 2-dB optical signal-to-noise ratio penalty, while there is no obvious penalty for the converted label.
The Relationship of Oxygen Transport and Cardiac Index for the Prevention of Sickle Cell Crises

The formation of deoxyhemoglobin S (deoxy-Hb S) polymers is the key triggering event for the complex pathophysiologic manifestations of sickle cell anemia (SCA). This polymer formation is associated with a marked right-shifted oxyhemoglobin dissociation curve (decreased affinity, increased P50), which results in a decrease in arterial oxygen saturation (SaO2. There is a delay period ("delay time") from the formation of deoxy-Hb S to polymerization that is markedly sensitive (to the power of 30-40) to the concentration and solubility changes of deoxy-Hb S. Deoxy-Hb S polymer formation leads to sickle cell vaso-occlusion, a unique characteristic of SCA. This theoretical study, which views SCA as a disease of oxygen transport, provides a novel framework to suggest that a small to modest increase in cardiac index (by decreasing the P50 and thus increasing the SaO2) could change the distribution of the delay times (sec) such that the balance between occlusion and opening of microcirculatory vessels is shifted favoring the opening of these vessels, therefore disfavoring vaso-occlusion. Our approach integrates a mathematical model of oxygen transport in SCA with: (1) the expression relating the solubility of deoxy-Hb S to SaO2, and (2) the kinetic expression relating the delay time to the solubility of deoxy-Hb S.
Current Dipole Images and Reference Potentials

The paper reviews the application of image theory to the problem of a current dipole in a homogeneous conducting medium where the boundary is a plane or circular cylinder, and shows how the technique applies to the case of a radial dipole in a spherical volume. The use of images for arbitrary shaped volumes is then considered. A rough criterion is developed and the approximation checked for the case of a "horizontal" dipole in a sphere. Finally the question of zero potentials is reviewed in the context of the previous work and in general.
Targeting DOT1L and HOX gene expression in MLL-rearranged leukemia and beyond

Leukemias harboring mixed-lineage leukemia gene (MLL1) abnormalities are associated with poor clinical outcomes, and new therapeutic approaches are desperately needed. Rearrangement of the MLL1 gene generates chimeric proteins that fuse the NH3 terminus of MLL1 to the COOH terminus of its translocation partners. These MLL1 fusion oncoproteins drive the expression of homeobox genes such as HOXA cluster genes and myeloid ecotropic viral integration site 1 homolog (MEIS1), which are known to induce leukemic transformation of hematopoietic progenitors. Genomewide histone methylation studies have revealed that the abnormal expression of MLL1 fusion target genes is associated with high levels of H3K79 methylation at these gene loci. The only known enzyme that catalyzes methylation of H3K79 is disruptor of telomeric-silencing 1-like (DOT1L). Loss-of-function mouse models, as well as small molecular inhibitors of DOT1L, illustrate that leukemias driven by MLL1 translocations are dependent on DOT1L enzymatic activity for proliferation and for the maintenance of HOXA gene expression. Furthermore, DOT1L also appears to be important for HOXA gene expression in other settings including leukemias with select genetic abnormalities. These discoveries have established a foundation for disease-specific therapies that target chromatin modifications in highly malignant leukemias harboring specific genetic abnormalities. This review focuses on the molecular mechanisms underlying MLL1 translocation-driven leukemogenesis and the latest progress on DOT1L-targeted epigenetic therapies for MLL1-rearranged and other leukemias.
Classical roots for a modern materials-energy analysis

Abstract Starting from a physiological analogy with the nutrition of living bodies, classical theorists from Hobbes to Senior and J.S. Mill developed a nascent materials-flow analysis of production which recognized an underlying physical interdependence in economic activities. Neoclassical theory, by contrast, took its tools and methods from analytical mechanics. It not only ignored material and energy flows from and to the environment, its basic physical assumptions (marginal productivity) are inconsistent with the principles governing material and energy transformations. The development of an ecological economics requires a radical reformulation of economic theory. This paper suggests that a synthesis of the classical production model with the insights of an ecological and systems approach offers an important direction for the future integration of a physical, informational and organizational approach to economic activity.
Review of published studies of kidney, liver, and gastrointestinal birth defects in fetal alcohol spectrum disorders.

OBJECTIVE: Review of published studies of birth defects of the renal, liver, and gastrointestinal organ systems in subjects with fetal alcohol spectrum disorders (FASD). METHOD: We searched PubMed (http://www.pubmed.gov) using the following terms: fetal alcohol syndrome and: gastrointestinal tract, kidney, liver, and congenital abnormalities for all years and English only citations. RESULTS: We located 12 studies of FASD and defects of or functional impairments for the liver, 12 of renal abnormalities, and only two with gastrointestinal defects. We did not identify specific patterns of malformations or functional deficits for any of the three organ systems. The existing literature suggests a series of nonspecific outcomes in FASD. CONCLUSIONS: Fetal alcohol spectrum disorder includes a diagnostic category of alcohol-related birth defects which is clinically difficult to apply. This study adds to the existing literature on birth defects in FASD which is still very limited. The categorical diagnosis of alcohol-related birth defects requires additional research to determine if a specific pattern of organ specific abnormalities or functional deficits emerges in subjects with FASD. Birth Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc.
Neural Circuitry Responsible for Sleep and Wakefulness

Research over the past 50 years has determined that specific neurons in the brain are responsible for generating waking, non-REM sleep, and REM sleep. Some of the neurons responsible for keeping us awake are also involved in regulating energy metabolism. One such arousal neuronal population contains the neuropeptide hypocretin, also known as orexin. The HCRT neurons are located in the hypothalamus, an area that also contains other neurons regulating energy metabolism. The hypocretin neurons are most active during waking and silent during sleep, and their activity has been shown to regulate brown adipose tissue (BAT) thermogenesis. The hypocretin neurons are also activated by low glucose levels and shut off when the glucose levels increase. Thus, the activity of the hypocretin neurons is linked to energy metabolism. Based on this relationship, it is easy to see how inadequate sleep or even frequent arousals during sleep, as occurs in obstructive sleep apnea, will affect energy metabolism and adiposity.
Hand bone mineral density is associated with both total hip and lumbar spine bone mineral density in post-menopausal women with RA

Objective. RA is associated with localized bone loss in the hands, as well as generalized osteoporosis. We evaluated the relationship between hand digital X-ray radiogrammetry BMD (DXR-BMD) and total hip and lumbar spine BMD. Methods. We conducted a cross-sectional study of 138 post-menopausal women with RA. The DXR-BMD was calculated based on digitized hand radiographs. Measurements of the total hip and lumbar spine BMD were performed by a DXA-BMD (BMDa) scan. Patient and physician questionnaires and laboratory samples supplied information on relevant covariates. Separate multivariate linear regression models were constructed to determine the cross-sectional relationship between hand DXR-BMD (independent variable) and total hip or lumbar spine BMD (dependent variables). Results. The cohort comprised women with a median age of 61 years and RA disease duration of 13 years. Seventy-six per cent were either RF and/or anti-cyclic citrullinated peptide (anti-CCP) positive and most had moderate disease activity [median disease activity score-28 joint count (DAS28) 3.7]. Hand DXR-BMD was significantly associated with total hip BMD (b ¼ 0.61; P < 0.0001) and lumbar spine BMD (b ¼ 0.62; P < 0.0008) in adjusted models. Conclusions. This study suggests that hand DXR-BMD is associated with both the total hip and lumbar spine BMD among post-menopausal women with RA. The relationship between bone loss in the hands and generalized osteoporosis should be further explored in longitudinal studies of patients with RA.
Language-modeling kernel based approach for information retrieval

In this presentation, we propose a novel integrated information retrieval approach that provides a unified solution for two challenging problems in the field of information retrieval. The first problem is how to build an optimal vector space corresponding to users' different information needs when applying the vector space model. The second one is how to smoothly incorporate the advantages of machine learning techniques into the language modeling approach. To solve these problems, we designed the language-modeling kernel function, which has all the modeling powers provided by language modeling techniques. In addition, for each information need, this kernel function automatically determines an optimal vector space, for which a discriminative learning machine, such as the support vector machine, can be applied to find an optimal decision boundary between relevant and nonrelevant documents. Large-scale experiments on standard test-beds show that our approach makes significant improvements over other state-of-the-art information retrieval methods. © 2007 Wiley Periodicals, Inc.
Medical and information technologies converge

Information technology offers medical science tools to collect, process, store, and communicate clinical data. Healthcare institutions have adapted standards-based data communication technologies that allow easy implementation of communications infrastructure. As clinical and information technologies have converged, two trends have emerged: the widespread use of commercial off-the-shelf hardware and software and the use of standards-based communication technologies. Technical support for these complex systems requires an integrated, "end-to-end" view and staff who are knowledgeable of both clinical and computer technologies. In this article, examples of new computerized medical devices are discussed as well as the support and support staff implications of the ever-growing influence of IT on clinical systems.
Slow magic: psychoanalysis and "the disenchantment of the world".

Freud's work can be situated in terms of the debate between Enlightenment and anti-Enlightenment thought. The attempts of both sides to claim Freud for their position have merit, but they miss the crucial point: namely, that the tension between its Enlightenment and anti-Enlightenment tendencies is what gives Freud's thinking much of its vitality and depth. The task that faces the interpreter is therefore to elucidate that tension and assess the alignment of forces between the two strands in his thought. An examination of the concept of magic in Freud's theory provides an opportunity to pursue this interpretive task. Although the Enlightenment position he often seems to embrace advocates the complete elimination of magic, many “magical” elements remain in his theory and clinical practice. Nor should this situation be deplored, for the ambition to completely exorcise “enchantment” from human experience is one of the misguided excesses of the Enlightenment. The question of an appropriate fate for magic in p...
Measuring Primary Care for Children of Latino Farmworkers: Reliability and Validity of the Parent's Perceptions of Primary Care Measure (P3C)

This study evaluates the feasibility, reliability, and validity of the Parent’s Perceptions of Primary Care measure (P3C) in an underserved population: children of Latino farm workers. Bilingual research assistants verbally administered the P3C, as well as a measure of child health-related quality of life (HRQL: the PedsQL™ 4.0) and demographic questions to 297 Latino farm worker parents of young children, in San Diego and Imperial Counties. The P3C was found to be feasible, as measured by a very low percent of missing/do not know values. Internal consistency reliability for the Total Scale and most subscales was strong. The P3C’s validity was demonstrated through factor analysis of the subscales, by showing that scores were lower for children without a regular physician and for children experiencing foregone health care, and by demonstrating that P3C scores were related to HRQL. The P3C can be useful to various stakeholders in measuring primary care for vulnerable populations.
In search of near-optimal optimization phase orderings

Phase ordering is a long standing challenge for traditional optimizing compilers. Varying the order of applying optimization phases to a program can produce different code, with potentially significant performance variation amongst them. A key insight to addressing the phase ordering problem is that many different optimization sequences produce the same code. In an earlier study, we used this observation to restate the phase ordering problem to concentrate on finding all distinct function instances that can be produced due to different phase orderings, instead of attempting to generate code for all possible optimization sequences. Using a novel search algorithm we were able to show that it is possible to exhaustively enumerate the set of all possible function instances that can be produced by different phase orderings in our compiler for most of the functions in our benchmark suite [1]. Finding the optimal function instance within this set for almost any dynamic measure of performance still appears impractical since that would involve execution/simulation of all generated function instances. To find the dynamically optimal function instance we exploit the observation that the enumeration space for a function typically contains a very small number of distinct control flow paths. We simulate only one function instance from each group of function instances having the identical control flow, and use that information to estimate the dynamic performance of the remaining functions in that group. We further show that the estimated dynamic frequency counts obtained by using our method correlate extremely well to simulated processor cycle counts. Thus, by using our measure of dynamic frequencies to identify a small number of the best performing function instances we can often find the optimal phase ordering for a function within a reasonable amount of time. Finally, we perform a case study to evaluate how adept our genetic algorithm is for finding optimal phase orderings within our compiler, and demonstrate how the algorithm can be improved.
Logics containing K 4. Part II 1

There are two main lacunae in recent work on modal logic: a lack of general results and a lack of negative results. This or that logic is shown to have such and such a desirable property, but very little is known about the scope or bounds of the property. Thus there are numerous particular results on completeness, decidability, finite model property, compactness, etc., but very few general or negative results. In these papers I hope to help fill these lacunae. This first part contains a very general completeness result. Let I n be the axiom that says there are at most n incomparable points related to a given point. Then the result is that any logic containing K4 and I n is complete. The first three sections provide background material for the rest of the papers. The fourth section shows that certain models contain no infinite ascending chains, and the fifth section shows how certain elements can be dropped from the canonical model. The sixth section brings the previous results together to establish completeness, and the seventh and last section establishes compactness, though of a weak kind. All of the results apply to the corresponding intermediate logics.
Systematic genome-wide screens of gene function

By using genome information to create tools for perturbing gene function, it is now possible to undertake systematic genome-wide functional screens that examine the contribution of every gene to a biological process. The directed nature of these experiments contrasts with traditional methods, in which random mutations are induced and the resulting mutants are screened for various phenotypes. The first genome-wide functional screens in Caenorhabditis elegans and Drosophila melanogaster have recently been published, and screens in human cells will soon follow. These high-throughput techniques promise the rapid annotation of genomes with high-quality information about the biological function of each gene.
High-Level Power Estimation and Low-Power Design Space Exploration for FPGAs

In this paper, we present a simultaneous resource allocation and binding algorithm for FPGA power minimization. To fully validate our methodology and result, our work targets a real FPGA architecture - Altera Stratix FPGA, which includes generic logic elements, DSP cores, and memories, etc. We design a high-level power estimator for this architecture and evaluate its estimation accuracy against a commercial gate-level power estimator - Quartus II PowerPlay Analyzer. During the synthesis stage, we pay special attention to interconnections and multiplexers. We concentrate on resource allocation and binding tasks because they are the key steps to determine the interconnections. We use a novel approach to explore the design space. Experimental results show that our high-level power estimator is 8.7% away from PowerPlay Analyzer. Meanwhile, we are able to achieve a significant amount of power reduction (32%) with better circuit speed (16%) compared to a traditional resource allocation and binding algorithm.
Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential

Mammalian Bcl-x(L) protein localizes to the outer mitochondrial membrane, where it inhibits apoptosis by binding Bax and inhibiting Bax-induced outer membrane permeabilization. Contrary to expectation, we found by electron microscopy and biochemical approaches that endogenous Bcl-x(L) also localized to inner mitochondrial cristae. Two-photon microscopy of cultured neurons revealed large fluctuations in inner mitochondrial membrane potential when Bcl-x(L) was genetically deleted or pharmacologically inhibited, indicating increased total ion flux into and out of mitochondria. Computational, biochemical, and genetic evidence indicated that Bcl-x(L) reduces futile ion flux across the inner mitochondrial membrane to prevent a wasteful drain on cellular resources, thereby preventing an energetic crisis during stress. Given that F(1)F(O)-ATP synthase directly affects mitochondrial membrane potential and having identified the mitochondrial ATP synthase β subunit in a screen for Bcl-x(L)-binding partners, we tested and found that Bcl-x(L) failed to protect β subunit-deficient yeast. Thus, by bolstering mitochondrial energetic capacity, Bcl-x(L) may contribute importantly to cell survival independently of other Bcl-2 family proteins.
Chemical Bond Distribution and Short Range Order in Non-Oxide Ciialcogenide Glasses. Results from NMR Spectroscopy

Solid-state 31P MAS-NMR provides powerful insights into the local order of phosphorus selenide based glasses. Specifically, it allows a quantitative characterization of the melt equilibrium PSe3/2 + Se -> Se=PSe3/2 describing the stability of four-coordinate P atoms. Using this technique, the effect of isovalent substitution by As, and Te, and of other glass constituents Ge and Tl on this equilibrium and on the quantitative phosphorus speciation is studied in detail.
Microscopic stress-induced magnetization changes in a fracture (1 1 1) surface of Terfenol-D observed with magnetic force microscopy

Abstract We have imaged mechanically polished and fractured (1 1 1) surfaces of Terfenol-D using magnetic force microscopy (MFM), and also the fracture surface during application of in situ applied stresses. The theory of James and Kinderlehrer (Phil. Magn. B 68 (1993) 237) has been used to explain some of the observed domain structures. Although some imaged domain structures are not predicted, there is general agreement with the theory. Observations indicate applied stress results in domain wall motion between existing domains as well as nucleation of new domains.