cssi/SciSciGPT-SciSciNet huggingface dataset:
Fluorine-19 nuclear magnetic resonance study of 5-fluorotryptophan-labeled histidine-binding protein J of Salmonella typhimurium

Abstract Fluorine-19 nuclear magnetic resonance has been used to investigate the histidinebinding protein J from Salmonella typhimurium. The protein has been labeled with fluorine-19 by growing the bacterial cells of a tryptophan auxotroph in the presence of 5-fluorotryptophan. Incorporation of up to 70% was achieved. The binding of l -histidine to the 19F-labeled protein is not affected by the isotopic labeling. The protein contains one tryptophan residue, giving rise to a single 19F resonance. Upon binding l -histidine to 19F-labeled histidine-binding protein J, the observed 19F resonance is shifted downfield by about 0.6 parts per million, indicating a conformational change of the protein molecule and a more hydrophobic environment for the 19F nucleus. Additional fluorescence experiments confirm that the tryptophan residue is located inside the hydrophobic core of the protein. 19F spin-lattice relaxation times of the 19F-labeled protein as a function of temperature show no difference between the free protein and the protein-histidine complex. However, the linewidth for the free protein is much larger than that of the protein-substrate complex. This can be explained by slow fluctuations between different conformations of the free protein molecule having slightly different 19F chemical shifts. Both with and without the substrate, the tryptophan residue is immobile inside the protein molecule as shown by the total disappearance of the 19F signal upon broadband irradiation at the 1H frequency. Also, the 19F spin-lattice relaxation times indicate that the protein is a rather rigid structure, in which rapid motions of the tryptophan residue on the time scale of 10−8 second are not prominent.
Communication About Child Development During Well-Child Visits: Impact of Parents’ Evaluation of Developmental Status Screener With or Without an Informational Video

BACKGROUND. The American Academy of Pediatrics recommends periodic administration of standardized developmental screening instruments during well-child visits to facilitate timely identification of developmental delay. However, little is known about how parents and physicians communicate about child development or how screening impacts communication. OBJECTIVE. Our goal was to examine whether parent-physician communication about child development is affected by (1) administration of a developmental screen or (2) video presentation on child development before well-child visits. METHODS. Six primary care pediatricians in a practice serving predominantly Medicaid-insured children participated. Fifteen parents of children 9 to 31 months of age per pediatrician were assigned to 1 of 3 previsit conditions (n = 89): (1) usual care; (2) parent completed the Parents’ Evaluation of Developmental Status screen; or (3) parent viewed 5-minute “activation” video before completing the Parents’ Evaluation of Developmental Status. Visits were audiorecorded and coded by blinded raters using a classification system that assesses communication content. Outcomes included visit length, physicians’ questions, information giving, reassurance or counseling about development, and parents’ concerns and requests for developmentally related services. RESULTS. Mean visit duration was similar for the 3 groups (22.5 minutes). Physicians made more information-giving and counseling statements about development and raised more developmental concerns in group 3 (video plus the Parents’ Evaluation of Developmental Status) than in group 1 (usual care) visits. A trend toward increased use of such communication was also seen in group 2 (Parents’ Evaluation of Developmental Status only). Parents were more likely to raise a developmental concern in group 3 than in group 1. No parent requested early intervention, therapy, or other related services. CONCLUSIONS. Use of a validated screening test did not increase average visit duration, an important consideration in primary care. Although use of the Parents’ Evaluation of Developmental Status alone led to some increase in parent-physician communication about development and developmental concerns, additional increase in communication was seen with the addition of a brief parent activation video shown before the Parents’ Evaluation of Developmental Status was completed.
Indian hedgehog synchronizes skeletal angiogenesis and perichondrial maturation with cartilage development

A null mutation in the morphogen Indian hedgehog (IHH) results in an embryonic lethal phenotype characterized by the conspicuous absence of bony tissue in the extremities. We show that this ossification defect is not attributable to a permanent arrest in cartilage differentiation, since Ihh -/- chondrocytes undergo hypertrophy and terminal differentiation, express angiogenic markers such as Vegf , and are invaded, albeit aberrantly, by blood vessels. Subsequent steps, including vessel expansion and persistence, are impaired, and the net result is degraded cartilage matrix that is devoid of blood vessels. The absence of blood vessels is not because the Ihh -/- skeleton is anti-angiogenic; in fact, in an ex vivo environment, both wild-type and Ihh mutant vessels invade the Ihh -/- cartilage, though only wild-type vessels expand to create the marrow cavity. In the ex vivo setting, Ihh -/- cells differentiate into osteoblasts and deposit a bony matrix, without benefit of exogenous hedgehog in the new environment. Even more surprising is our finding that the earliest IHH-dependent skeletal defect is obvious by the time the limb mesenchyme segregates into chondrogenic and perichondrogenic condensations. Although Ihh -/- cells organize into chondrogenic condensations similar in size and shape to wild-type condensations, perichondrial cells surrounding the mutant condensations are clearly faulty. They fail to aggregate, elongate and flatten into a definitive, endothelial cell-rich perichondrium like their wild-type counterparts. Normally, these cells surrounding the chondrogenic condensation are exposed to IHH, as evidenced by their expression of the hedgehog target genes, patched ( Ptch ) and Gli1 . In the mutant environment, the milieu surrounding the cartilage - comprising osteoblast precursors and endothelial cells - as well as the cartilage itself, develop in the absence of this important morphogen. In conclusion, the skeletal phenotype of Ihh -/- embryos represents the sum of disturbances in three separate cell populations, the chondrocytes, the osteoblasts and the vasculature, each of which is a direct target of hedgehog signaling.
Limited but Evolving: The Political Economy of Social Protections in Nepal

AbstractNepal’s awakening to growing social protection needs occurred only lately with most policies introduced in the 1990s. While comparable by Asian and particularly South Asian standards, these protections are limited and inconsistent. This article takes stock of social protection policies in Nepal with particular emphasis on the extent of coverage relative to needs. It explores the political economy, demand and political contexts to explain why social protections have developed the way they have in Nepal’s modern history. The understanding of Nepal’s struggle with this globally contested issue also helps draw parallels to other low-income countries.
Amygdala-kindled postictal inhibition: Effect of intertrial intervals on repeated days

Abstract Fully amygdala-kindled rats with stable afterdischarge durations and seizure ranks of five were evaluated with suprathreshold stimulations (400 μA) at variable interstimulus intervals. Subjects were stimulated either once a day or four times a day at one of five interstimulus intervals (5, 15, 30, 60, or 180 min) for 5 days. All subjects were tested under each of the six paradigms. Profound inhibition of seizure rank and afterdischarge duration occurred daily with intertrial stimulation times of 30 min or less. The initial stimulations each day at these intertrial intervals showed no significant residual inhibition from the stimulations of the previous day. The longer intertrial intervals of 60 and 180 min demonstrated little inhibition of elicited seizures on day 1 for trials 2 through 4; however, after the 1st day, increased inhibition was noted for trials 2 through 4 at the 60-min intertrial interval with relatively little inhibition noted for the first trial of each day at this interval. At the longest interval tested (180 min), a significant (P
Supersonic Coaxial Jet Experiment for CFD Code Validation

A supersonic coaxial jet facility has been designed to provide experimental data suitable for the validation of CFD codes used to analyze high-speed propulsion flows. The center jet is of a light gas and the coflow jet is of air, and the mixing layer between them is compressible. Various methods have been employed in characterizing the jet flow field, including schlieren visualization, pitot, total temperature and gas sampling probe surveying, and RELIEF velocimetry. A Navier-Stokes code has been used to calculate the nozzle flow field and the results compared to the experiment.
ON THE FRAGMENTATION OF THE PROJECTILE IN RELATIVISTIC HEAVY-ION COLLISIONS

Abstract The fragmentation of the projectile in relativistic heavy-ion reactions is usually described in terms of a two-step model called abrasion-ablation. The abrasion part is reformulated in the framework of the Boltzmann equation. The results are compared with other approaches and with experiment.
Genetic abnormalities in sporadic parathyroid adenomas.

We analyzed genomic DNA from 43 sporadic benign parathyroid adenomas for rearrangements of the PTH gene, and for point mutations of the H-ras (codons 12, 13, and 61), N-ras (codons 12,13, and 61), and K-ras (codons 12 and 13) genes. One of 43 parathyroid adenomas showed a chromosome 11 rearrangement involving both the PTH gene on the short arm of chromosome 11 (at band pl5) and a locus on the long arm (11ql3). This rearrangement was indistinguishable from one that was previously described in a parathyroid adenoma by Arnold et al., indicating that this may be an important contributor to tumorigenesis in a small subset of patients with parathyroid adenoma. H-ras, K-ras, and N-ras oncogene activation by point mutation at codons 12, 13, or 61, known to occur in many tumors, could not be detected in any parathyroid adenoma.
Inhibition of glycogen phosphorylase (GP) by CP-91,149 induces growth inhibition correlating with brain GP expression

Abstract The role of glycogenolysis in normal and cancer cells was investigated by inhibiting glycogen phosphorylase (GP) with the synthetic inhibitor CP-91,149. A549 non-small cell lung carcinoma (NSCLC) cells express solely the brain isozyme of GP, which was inhibited by CP-91,149 with an IC50 of 0.5 μM. When treated with CP-91,149, A549 cells accumulated glycogen with associated growth retardation. Treated normal skin fibroblasts also accumulated glycogen with G1-cell cycle arrest that was associated with inhibition of cyclin E-CDK2 activity. Overall, cells expressing high levels of brain GP were growth inhibited by CP-91,149 correlating with glycogen accumulation whereas cells expressing low levels of brain GP were not affected by the drug. Analyses of 59 tumor cell lines represented in the NCI drug screen identified that every cell line expressed brain GP but the profile was dominated by a few highly GP expressing cell lines with lower than mean GP-a enzymatic activities. The correlation program, COMPARE, identified that the brain GP protein measured in the NCI cell lines corresponded with brain GP mRNA expression, ADP-ribosyltransferase 3, and colony stimulating factor 2 receptor α in the 10,000 gene microarray database with similar correlation coefficients. These results suggest that brain GP is present in proliferating cells and that high protein levels correspond with the ability of CP-91,149 to inhibit cell growth.
Intake of purine‐rich foods, protein, and dairy products and relationship to serum levels of uric acid: The Third National Health and Nutrition Examination Survey

Objective Various commonly consumed foods have long been suspected of affecting the serum uric acid level, but few data are available to support or refute this impression. Our objective was to evaluate the relationship between dietary factors and serum uric acid levels in a nationally representative sample of men and women in the US. Methods Using data from 14,809 participants (6,932 men and 7,877 women) ages 20 years and older in the Third National Health and Nutrition Examination Survey (for the years 1988–1994), we examined the relationship between the intake of purine-rich foods, protein, and dairy products and serum levels of uric acid. Diet was assessed with a food-frequency questionnaire. We used multivariate linear regression to adjust for age, sex, total energy intake, body mass index, use of diuretics, β-blockers, allopurinol, and uricosuric agents, self-reported hypertension and gout, serum creatinine level, and intake of alcohol. Results The serum uric acid level increased with increasing total meat or seafood intake and decreased with increasing dairy intake. After adjusting for age, the differences in uric acid levels between the extreme quintiles of intake were 0.48 mg/dl for total meat (95% confidence interval [95% CI] 0.34, 0.61; P < 0.001 for trend), 0.16 mg/dl for seafood (95% CI 0.06, 0.27; P = 0.005 for trend), and –0.21 mg/dl for total dairy intake (95% CI –0.37, –0.04; P = 0.02 for trend). After adjusting for other covariates, the differences between the extreme quintiles were attenuated but remained significant (P < 0.05 for all comparisons). The total protein intake was not associated with the serum uric acid level in multivariate analyses (P = 0.74 for trend). Those who consumed milk 1 or more times per day had a lower serum uric acid level than did those who did not drink milk (multivariate difference –0.25 [95% CI –0.40, –0.09]; P < 0.001 for trend). Similarly, those who consumed yogurt at least once every other day had a lower serum uric acid level than did those who did not consume yogurt (multivariate difference –0.26 [95% CI –0.41, –0.12]; P < 0.001 for trend). Conclusion These findings from a nationally representative sample of adults in the US suggest that higher levels of meat and seafood consumption are associated with higher serum levels of uric acid but that total protein intake is not. Dairy consumption was inversely associated with the serum uric acid level.
SU-GG-T-177: Determination of SOBP PDD for Therapeutic Proton Beams

Purpose: We have developed a Cimmino algorithm to calculate the percentage depth dose (PDD) of spread‐out Bragg peaks (SOBP) for megavoltage proton beams. Method and Materials: For patient underwent clinical proton treatment using scattered beams, it is often desirable to determine the shape of SOBP PDD for determination of dose at points away from the beam modulation width. For patient prescription, the SOBP is often prescribed by two parameters, the range of SOBP, R, defined as the distance from the surface to the distance that corresponding to 90% of the maximum dose and the modulation width of SOBP, M, defined as the width of the uniform dose within 90% of the maximum dose. Often, the shape of the SOBP PDD is unknown and has to be calculated from the file that determines the temporal dependence of nozzle equivalent thickness (NET) profiles of the energy modulation wheel. We have developed a Cimmino algorithm to calculate the SOBP PDD from the pristine PDD by constraint the PDD to be constant within M and have a range of R. Results: SOBP PDD calculated by the Cimmino algorithm agrees reasonably well with SOBP PDD determined from the modulation wheel. They agree at most depths and are slightly different at the entrance. The difference is attributed to the difference in weighing the pristine PDD. Conclusion: This algorithm is ideally suitable for calculating SOBP PDD suitable for patient‐specific MU verification for proton beams. As a result, one no longer needs the energy modulation file output for calculation of dose at arbitrary depth.
New arene cis-dihydrodiol metabolites from β-bromostyrenes

Abstract Both ( E )- and ( Z )-β-bromostyrenes are substrates for toluene dioxygenase from Escherichia coli (JM109, pDTG601) and yield the corresponding diol metabolites in yields of 1 g/L, respectively.
Cardiovascular repair with bone marrow-derived cells.

While bone marrow (BM)-derived cells have been comprehensively studied for their propitious pre-clinical results, clinical trials have shown controversial outcomes. Unlike previously acknowledged, more recent studies have now confirmed that humoral and paracrine effects are the key mechanisms for tissue regeneration and functional recovery, instead of transdifferentiation of BM-derived cells into cardiovascular tissues. The progression of the understanding of BM-derived cells has further led to exploring efficient methods to isolate and obtain, without mobilization, sufficient number of cell populations that would eventually have a higher therapeutic potential. As such, hematopoietic CD31+ cells, prevalent in both bone marrow and peripheral blood, have been discovered, in recent studies, to have angiogenic and vasculogenic activities and to show strong potential for therapeutic neovascularization in ischemic tissues. This article will discuss recent advancement on BM-derived cell therapy and the implication of newly discovered CD31+ cells.
Structure and tectonics of the Manila trench system, Western Luzon, Philippines

Abstract The Manila Trench subduction zone is an active convergent plate margin between the South China Sea and the northern Philippines. The Manila Trench is associated with an east-dipping Benioff zone beneath Luzon, a well-developed forearc basin system and a volcanic arc. The Luzon Trough forearc basin system contains up to 4.5 km of Cenozoic sediments. Trench strata are folded and faulted at the base of the trench slope. The major decollement at the Manila Trench usually forms near the unconformity separating the pelagic from the turbidite sediments in the trench. The accretion of turbidite sediments deposited in the Manila Trench has resulted in the upbuilding of an accretionary prism which forms the seaward margin of the forearc basin system. The uplifted Zambales ophiolite and its offshore extension form the landward side of the forearc basin. Uplift of the forearc basins is confined to a narrow zone near the intersection of the relict spreading center within the South China Sea plate. The forearc north of Lingayan Gulf is disrupted by active, northerly trending fault systems that extend offshore from the Luzon Central Valley and from the southern Cordillera Central. The Early Miocene uplift and tilting of the Zambales ophiolite may mark the beginning of subduction at the Manila Trench. We infer that the long-term average convergence rate across the Manila Trench has been about 1 cm/yr and may be slowing in the north due to the collision of Taiwan with Eurasia.
Role of endothelium in chronic inflammatory synovitis.

ZIFF, M. Role of Endothelium in Chronic Inflammatory Synoritis. Tohoku J. Exp. Med., 1994, 173 (1), 183-188-The rheumatoid synovial membrane is infiltrated by chronic inflammatory cells. The major fraction of the infiltrating lymphocytes is composed of CD4+cells. A large number of studies of the composition of the T cell receptors of these lymphcytes have failed to demonstrate evidence of a dominant clonal population of T cells which is chacteristic of rheumatoid synovitis. Most of the T cells are polyclonal in nature. This report discusses the basis for this polyclonality. Current evidence is reviewed which supports the conclusion that T cells emigrate from postcapillary venules because they are in an activated state. The activated T cell is characterized by elevated expression and avidity of adhesion receptors capable of reacting with counterreceptors on the endothelial cells of postcapillary venules, leading to binding and emigration from the blood. The T cells are retained in the perivascular connective tissue because their adhesion receptors interact with counterreceptors on other mononuclear cells and on matrix proteins. The increased expression of adhesion receptors on the T cells may be a result of prior contact with antigen; increased expression of counterreceptors on the endothelial cells results from stimulation by cytokines released by local inflammatory cells. The interaction between T cell adhesion molecules and counterreceptors is independent of the immunological specificity of the T cell. Hence, the T cells of the rheumatoid synovium are largely polyclonal memory cells.
Radical Anions of Trifluoromethylated Perylene and Naphthalene Imide and Diimide Electron Acceptors

A series of electron-deficient perylene and naphthalene imides and diimides (1–4) with varying degrees of trifluoromethylation were synthesized. Single crystal X-ray analysis afforded detailed structural information, while spectroelectrochemical and EPR spectroscopy provided characterization of the radical anions of 1–4. This study reveals that trifluoromethylation of the imides and diimides makes their one-electron reduction potentials substantially more positive relative to the unsubstituted counterparts, while their other properties remain largely unchanged.
Dynamic theory of preferences: Habit formation and taste for variety

Abstract We analyze individual preferences over infinite horizon consumption choices. Our axioms provide the foundation for a recursive representation of the utility function that contains as particular cases the classical Koopmans representation (Koopmans (1960)) as well as the habit formation specification. We examine some of the consequences of our axiomatization by considering a standard consumer choice problem, and show that typically in the space of concave utility functions satisfying our axioms the consumer displays a taste for variety. The latter means that such a consumer selects optimally time variant consumption programs for any given time invariant sequence of commodities’ relative prices and for all possible sequences of market discount factors. In contrast, if a concave utility function satisfies Koopmans’ axioms the consumer does not display a taste for variety.
An autoradiographic study of RNA synthesis during maturation and germination of pollen grains of Hyoscyamus niger.

The pattern of RNA synthesis during maturation and germination of pollen grains ofHyoscyamus niger was studied using3H-uridine autoradiography. Incorporation of label during pollen maturation was periodic with peak RNA synthesis occurring in the uninucleate, nonvacuolate pollen grains and in the vegetative cell of the bicellular pollen grains. During the early stages of germination, isotope incorporation occurred predominantly in the nucleus of the vegetative cell with little or no incorporation in the generative cell. With the appearance of the pollen tube, incorporation of3H-uridine in the vegetative cell nucleus decreased and completely disappeared at later stages of germination. No incorporation of isotope was observed in the sperms formed in the pollen tube by the division of the generative cell. From a comparison of the results of this study with those of previous works on RNA synthesis during pollen embryogenesis in cultured anthers ofH. niger, it is concluded that in contrast to embryogenic development, there is no requirement for sustained RNA synthesis by the generative cell nucleus for normal gametophytic development.
Glutathione Conjugate-Mediated Toxicities

Glutathione (γ-glutamylcysteinylglycine; GSH) is the predominant intracellular nonprotein sulfhydryl present in the cytosol of animal and plant cells. GSH plays an integral role in a large number of biologically important reactions (Sies and Ketterer 1988; Taniguchi et al. 1989; Vina 1990). The numerous reactions that GSH participates in can be divided into those involving the γ-glutamyl moiety of the tripeptide and those of the sulfhydryl moiety. Those reactions involving the latter function can be further divided into either oxidation—reduction reactions or nucleophilic reactions. In its reduced form, GSH is a strong nucleophile and can react with electrophiles via a direct Sn2 reaction to form a thioether. These reactions may also be catalyzed by one or more of the cytosolic, microsomal, or mitochondrial GSH S-transferase isoenzymes. Most compounds that are conjugated with GSH are ultimately excreted in urine as the corresponding mercapturic acid, which are S-conjugates of N-acetylcysteine. Conjugation with GSH has usually been considered a detoxication reaction. The increased water solubility and the active secretion of organic acids by renal tubules greatly facilitates mercapturic acid excretion. However, the principal detoxication function of GSH conjugation, namely, the inactivation of a reactive electrophile by the initial attack of the GSH thiolate anion (Reed and Meredith 1985), does not necessitate mercapturate formation. Conjugation with GSH has now been implicated in the bioactivation of a variety of chemicals to mutagenic, carcinogenic, and cytotoxic metabolites. This chapter will describe the most recent advances in our knowledge of the mechanism(s) by which xenobiotic conjugations with GSH can result in toxicity.
A BRIEF HISTORY OF THE NEW WORLD FLYING SQUIRRELS: PHYLOGENY, BIOGEOGRAPHY, AND CONSERVATION GENETICS

I summarize our current understanding of the evolutionary origin and biogeographic history of the New World flying squirrels (Glaucomys). The emerging synthesis of flying squirrel systematics supports a monophyletic origin for the group in the early Miocene followed by a divergence of New World and Eurasian flying squirrels in the late Miocene. Today, the New World flying squirrels consist of 2 recognized species, G. sabrinus and G. volans. These 2 species are closely associated with the northern coniferous and deciduous hardwood forest biomes of North America, respectively, making them especially useful as biogeographic indicator species for these 2 forest types. Molecular systematic studies have revealed the presence of 2 distinct evolutionary lineages within G. sabrinus (a widespread Continental lineage and a more geographically restricted Pacific Coastal lineage). Bacular morphology and data from nuclear loci suggest recent or ongoing gene flow between these 2 lineages where they meet in the Pacific Northwest of North America. Populations of G. volans from eastern North America represent a 3rd distinct lineage within the genus. Mesoamerican flying squirrels (traditionally considered to be southern forms of G. volans) have not been examined with molecular data and may represent 1 or more additional lineages. From a biogeographic perspective, Quaternary climatic fluctuations and associated changes in the location and extent of forest habitats appear to have been important factors in promoting early evolutionary diversification within the genus; structuring of intraspecific patterns of genetic variation; and producing geographically isolated peripheral populations in high-elevation habitats at the southern extremes of each species’ range, several of which are now of conservation concern. These results have broad implications for understanding the Quaternary biogeography of the coniferous and deciduous forest biomes of North America.
Paper sheet control using steerable nips

Many high speed color printers require that sheets be accurately controlled in order to achieve a precise alignment of colors. To accomplish this goal, a steerable nips mechanism has been proposed as an actuator to propel sheets along the printer's paper path. This steerable nips mechanism allows the sheet to be precisely controlled in the longitudinal, lateral and skew directions. In this paper we develop a control strategy based on linearization by state feedback and dynamic surface control (DSC) to precisely control the position of the sheet. The proposed controller is able to move the sheet from an initial to a final state under the condition that the sheet has nonzero initial and final velocities. The system model is nonlinear and subject to four nonholonomic constraints. Two of these constraints are related to the fact that the velocities perpendicular to the wheels must be zero, and the other two constraints are due to the non-slip condition.
Cluster analysis using a validated self-organizing method: cases of problem identification

Kohonen's self-organizing feature maps (SOFM) are commonly used in cluster analysis for problem solving. However, given a set of sample data, the cluster analysis results obtained by using the standard SOFM method can vary depending on the setting of the parameters of the SOFM. To validate the cluster analysis results, information in addition to the data for the SOFM is required. This paper reports practical cases of cluster analysis using SOFM in conjunction with a measure of validation. In these cases, multivariate data of survey were used to identify problems through validated SOFM cluster analyses. Copyright © 2001 John Wiley & Sons, Ltd.
Mitochondrial OPA1, apoptosis, and heart failure

Aims Mitochondrial fusion and fission are essential processes for preservation of normal mitochondrial function. We hypothesized that fusion proteins would be decreased in heart failure (HF), as the mitochondria in HF have been reported to be small and dysfunctional. Methods and results Expression of optic atrophy 1 (OPA1), a mitochondrial fusion protein, was decreased in both human and rat HF, as observed by western blotting. OPA1 is important for maintaining normal cristae structure and function, for preserving the inner membrane structure and for protecting cells from apoptosis. Confocal and electron microscopy studies demonstrated that the mitochondria in the failing hearts were small and fragmented, consistent with decreased fusion. OPA1 mRNA levels did not differ between failing and normal hearts, suggesting post-transcriptional control. Simulated ischaemia in the cardiac myogenic cell line H9c2 cells reduced OPA protein levels. Reduction of OPA1 expression with shRNA resulted in increased apoptosis and fragmentation of the mitochondria. Overexpression of OPA1 increased mitochondrial tubularity, but did not protect against simulated ischaemia-induced apoptosis. Cytochrome c release from the mitochondria was increased both with reduction in OPA1 and with overexpression of OPA1. Conclusion This is the first report, to our knowledge, of changes in mitochondrial fusion/fission proteins in cardiovascular disease. These changes have implications for mitochondrial function and apoptosis, contributing to the cell loss which is part of the downward progression of the failing heart.
Determination of the chiral indices (n,m) of carbon nanotubes by electron diffraction

The atomic structure of a carbon nanotube can be defined by the chiral indices, (n,m), that specify its perimeter vector (chiral vector), with which the diameter and helicity are also determined. The fine electron beam available in a modern Transmission Electron Microscope (TEM) offers a unique and powerful probe to reveal the atomic structure of individual nanotubes. This article covers two aspects related to the use of the electron probe in the TEM for the study of carbon nanotubes: (i) to express the electron diffraction intensity distribution in the electron diffraction patterns of carbon nanotubes and (ii) to obtain the chiral indices (n,m) of carbon nanotubes from their electron diffraction patterns. For a nanotube of given chiral indices (n,m), the electron scattering amplitude from the carbon nanotube can be expressed analytically in closed form using the helical diffraction theory, from which its electron diffraction pattern can be calculated and understood. The reverse problem, i.e., assignment of the chiral indices (n,m) of a carbon nanotube from its electron diffraction pattern, is approached from the relationship between the electron diffraction intensity distribution and the chiral indices (n,m). The first method is to obtain indiscriminately the chiral indices (n,m) by reading directly the intensity distribution on the three principal layer lines, l1, l2, and l3, which have intensities proportional to the square of the Bessel functions of orders m, n, and n + m: Il1 ∝ |Jm (πdR)|2, Il2 ∝ |Jn (πdR)|2, and Il3 ∝ |Jn+m (πdR)|2. The second method is to obtain and use the ratio of the indices n/m = (2D1 − D2)/(2D2 − D1) in which D1 and D2 are the spacings of principal layer lines l1 and l2, respectively. Examples of using these methods are also illustrated in the determination of chiral indices of isolated individual single-walled carbon nanotubes, a bundle of single-walled carbon nanotubes, and multi-walled carbon nanotubes.
Information management for entomology screening.

The successful introduction of genetically modified (GM) crops has created a revolutionary transformation of the agricultural industry with GM crops currently planted on some 130 million acres. Historically, agricultural companies were involved in the discovery of conventional insecticide chemistries in processes that were very similar to those in the pharmaceutical industry. With the introduction of GM technologies, the process has radically changed. The new process is best described as the pharmaceutical equivalent of a very large-scale limited clinical trial conducted at the discovery stage. For example, unlike pharmaceutical screens, GM crop discovery screens frequently involve live insects challenged with complex protein–containing soups. Furthermore, the nature of the potential avenues for discovery mandates that assay models also support protein engineering, proteomics, and genomics efforts. The range in sample demand ranges from ultra-low to high throughput. Finally, regulatory and good business stewardship demands that data integrity and tractability is in place, from discovery through varietal introduction, to manage the information generated in support of a commercialized GM plant variety. The authors describe their discovery workflow and detail how they have customized a commercially available database software package to achieve an optimum configuration for entomology screening. (Journal of Biomolecular Screening 2004:37-43)
The Genetic Basis of Myelodysplastic Syndromes

Myelodysplastic syndrome (MDS) disorders are clonal diseases that often carry stereotypic chromosomal abnormalities. A smaller proportion of cases harbor point mutations that activate oncogenes or inactivate tumor suppressor genes. New technologies have accelerated the pace of discovery and are responsible for the identification of novel genetic mutations associated with MDS and other myeloid neoplasms. These discoveries have identified novel mechanisms in the pathogenesis of MDS. This article touches on the better known genetic abnormalities in MDS and explains in greater detail those that have been discovered more recently. Understanding how mutations lead to MDS and how they might cooperate with each other has become more complicated as the number of MDS-associated genetic abnormalities has grown. In some cases, these mutations have prognostic significance that could improve upon the various prognostic scoring systems in common clinical use.
Release of Ca2+ from the sarcoplasmic reticulum increases mitochondrial [Ca2+] in rat pulmonary artery smooth muscle cells

1. The Ca2+-sensitive fluorescent indicator rhod-2 was used to measure mitochondrial [Ca2+] ([Ca2+]m) in single smooth muscle cells from the rat pulmonary artery, while simultaneously monitoring cytosolic [Ca2+] ([Ca2+]i) with fura-2. 2. Application of caffeine produced an increase in [Ca2+]i and also increased [Ca2+]m. The increase in [Ca2+]m occurred after the increase in [Ca2+]i, and remained elevated for a considerable time after [Ca2+]i had returned to resting values. 3. The protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), which causes the mitochondrial membrane potential to collapse, markedly attenuated the increase in [Ca2+]m following caffeine application and also increased the half-time for recovery of [Ca2+]i to resting values. 4. Activation of purinoceptors with ATP also produced increases in both [Ca2+]i and [Ca2+]m in these smooth muscle cells. In some cells, oscillations in [Ca2+]i were observed during ATP application, which produced corresponding oscillations in [Ca2+]m and membrane currents. 5. This study provides direct evidence that Ca2+ release from the sarcoplasmic reticulum, either through ryanodine or inositol 1,4, 5-trisphosphate (InsP3) receptors, increases both cytosolic and mitochondrial [Ca2+] in smooth muscle cells. These results have potential implications both for the role of mitochondria in Ca2+ regulation in smooth muscle, and for understanding how cellular metabolism is regulated.
Evaluating vehicle inspection/maintenance programs using on-road emissions data. The Atlanta Reference Method.

On-road remote sensing data is an increasingly popular source of evaluation information for vehicle inspection/maintenance (I/M) programs. This article conducts one such remote sensing data evaluat...
The New Blue Horizon: Quantum Well Lasers From II-VI Semiconductors: Quantum Well Physics

Summary form only given, as follows. The ongoing developments in 11-VI blue/green diode lases call for detailed attention to the designs and modeling of gain in the active quantum well region in the ZnSE-based heterostructures. These include issues of many electron-hole Coulomb interaction, including 2dimensional excitonic effects. 18
Where Do Eggs Fit in a Heart-Healthy Diet?

Eggs make up a relatively small contribution to the energy consumption of the average American, in part because of the perception that the cholesterol content makes them a forbidden food for a heart-healthy diet. The relationship between egg cholesterol, blood cholesterol, and cardiovascular disease risk is complex and not clearly understood. In addition, eggs provide many valuable and bioavailable nutrients. Thus, the place of eggs in meal planning should be reconsidered while keeping in mind the diet and lifestyle recommendations of the American Heart Association.
Teaching the Quantal Exposition of the Unified Quantum Theory of Mechanics and Thermodynamics

The author presents his experience in teaching at a graduate level the quantal exposition of a new non-statistically based paradigm of physics and thermodynamics. This paradigm, called the Unified Quantum Theory of Mechanics and Thermodynamics, applies to all systems large or small (including one particle systems) either in a state of thermodynamic (i.e. stable) equilibrium or not in a state of thermodynamic equilibrium. It uses as its primitives inertial mass, force, and time and introduces the laws of thermodynamics in the most unambiguous and general formulations found in the literature. Starting with a precise definition of system and of state followed by statements and corollaries of the laws of thermodynamics, the thermodynamic formalism is developed without circularity and ambiguity. In this quantal exposition of the new paradigm, a brief review of the formalism of thermodynamics as a general science not limited to stable equilibrium and large (macroscopic) systems as well as a very brief summary of the three prevalent formalisms in classical physics are presented followed by a presentation and development of solutions for a number of elementary problems in quantum physics (e.g., a particle in a box, a harmonic oscillator, a rigid rotor, etc.). These solutions and the maximum entropy principle are then used in a constrained optimization to develop the canonical and grand canonical distributions for Fermi-Dirac and Bose-Einstein types of particles, i.e. for fermions and bosons. This is done without the use of analogies between statistical and thermodynamic results and without additional hypotheses such as the ergodic hypothesis of statistical mechanics. These distributions are then employed under various assumptions (i.e. the Boltzmann, constant-potential, point-particle, and continuous eigenvalue-spectrum approximations) to derive the corresponding thermodynamic property expressions for perfect, semi-perfect (ideal), and Sommerfeld gases as well as for mixtures of ionized and dissociated gases. In a similar fashion but with a change from a single- to a multi-particle partition function and with the addition of various inter-particle potentials for two-particle interactions (e.g., the Lennard-Jones potential, the square-well potential, etc.), expressions for the thermodynamic properties of dense gases are developed and presented. An initial version of this paper was published in July of 2006 in the proceedings of ECOS’06, Aghia Pelagia, Crete, Greece.
Gas chromatographic pathways for certain chloro-alkylammonium montmorillonites

A series of chloro-alkylammonium montmorillonites was produced by cation exchange from Na+-montmorillonite. Gas chromatographic data were obtained for light hydrocarbons and certain oxides of nitrogen. Surface area and X-ray powder diffraction studies were made on each organo-clay, making possible differentiation between possible chromatographic pathways. Adsorption of the gas molecules on the silicate sheet was determined to be the dominant chromatographic pathway for all gases studied.
Leakage reduction for the Siemens ModuLeaf

The Moduleaf, an add-on miniature multileaf collimator (MMLC) for the Siemens Oncor linear accelerator, provides high resolution field shaping with a maximum inter-leaf leakage dose of 1.50% at 6 MV. However, beyond the maximum treatment field size, the distribution of leakage and scatter along the y axis is different from that of the x axis, with maximum leakage values of 1.53% and 0.39%, respectively. Such differences can not be modeled in the Pinnacle treatment planning system. Also, within the 10 cm x 12 cm treatment region, leakage from the crack between closed leaf ends was 3.76%. To resolve these issues, gaps in the Moduleaf frame were filled with lead sheets, and the Siemens MLC was operated in MLC mode, rather than bank mode, so that a rectangle of 10.4 cm x 11 cm was formed with the MLC leaves closed behind the Y jaws, whose opening was 10.4 cm. This significantly reduced the difference between the leakage patterns in the x and y directions, with maximum leakage doses of 0.43% outside the treatment region and 1.67% near the crack between abutting Moduleaf leaves. The modification also reduced the mean square error between Pinnacle profiles and measured profiles in the tail region.
Evaluation of Pharmacokinetic/Pharmacodynamic Relationships of PD-0162819, a Biotin Carboxylase Inhibitor Representing a New Class of Antibacterial Compounds, Using In Vitro Infection Models

ABSTRACT The present study investigated the pharmacokinetic/pharmacodynamic (PK/PD) relationships of a prototype biotin carboxylase (BC) inhibitor, PD-0162819, against Haemophilus influenzae 3113 in static concentration time-kill (SCTK) and one-compartment chemostat in vitro infection models. H. influenzae 3113 was exposed to PD-0162819 concentrations of 0.5 to 16× the MIC (MIC = 0.125 μg/ml) and area-under-the-curve (AUC)/MIC ratios of 1 to 1,100 in SCTK and chemostat experiments, respectively. Serial samples were collected over 24 h. For efficacy driver analysis, a sigmoid maximum-effect ( E max ) model was fitted to the relationship between bacterial density changes over 24 h and corresponding PK/PD indices. A semimechanistic PK/PD model describing the time course of bacterial growth and death was developed. The AUC/MIC ratio best explained efficacy ( r 2 = 0.95) compared to the peak drug concentration ( C max )/MIC ratio ( r 2 = 0.76) and time above the MIC ( T >MIC) ( r 2 = 0.88). Static effects and 99.9% killing were achieved at AUC/MIC values of 500 and 600, respectively. For time course analysis, the net bacterial growth rate constant, maximum bacterial density, and maximum kill rate constant were similar in SCTK and chemostat studies, but PD-0162819 was more potent in SCTK than in the chemostat (50% effective concentration [EC 50 ] = 0.046 versus 0.34 μg/ml). In conclusion, basic PK/PD relationships for PD-0162819 were established using in vitro dynamic systems. Although the bacterial growth parameters and maximum drug effects were similar in SCTK and the chemostat system, PD-0162819 appeared to be more potent in SCTK, illustrating the importance of understanding the differences in preclinical models. Additional studies are needed to determine the in vivo relevance of these results.
The molecular perspective: polycyclic aromatic hydrocarbons.

The Oncologist 2004;9:469-470 www.TheOncologist.com Smoking is an unlikely method for delivery of small molecules. After all, it burns up most of your material. However, smoking is prevalent because it delivers a fine, volatile smoke of the remaining material, which rapidly enters the body at the point where the bloodstream is most exposed. By definition, the flame cannot be clean; it must allow the nicotine, cannabinoids, or opiates to survive in the smoke. Unfortunately, this flame also performs a multitude of uncontrolled chemical reactions, yielding thousands of exotic, and occasionally carcinogenic, compounds. Among this collection of incomplete combustion products is a family of polycyclic aromatic hydrocarbons. These are large, flat molecules built of a collection of fused benzene-like rings. These compounds show up whenever organic material is burned: when smoking, at barbeques, and in the slower geological combustion that formed oil and coal. Polycyclic aromatic hydrocarbons, since they are rich in carbon and are hydrophobic, pass easily through cell membranes and travel quickly into cells. Once inside, cells use their detoxification machinery to try to remove it. The Fundamentals of Cancer Medicine The Oncologist
Effect of exercise on anthropometric measures and serum lipids in older individuals: a systematic review and meta-analysis

Objectives Overweight and obesity are increasing in individuals over age 60 years. This systematic review quantifies the effect of exercise on body mass index (BMI), waist circumference (WC) and lipids in overweight and obese individuals over the age of 60 years. Settings Nine randomised controlled trials conducted in Brazil, Great Britain, Iceland, Japan and the USA compared aerobic and/or resistance exercise with a control group. Participants Final analysis reviewed 1166 participants over the age of 60 years for 3–9 months. Primary outcome measures This study reviewed the effects of exercise on BMI, WC and low-density lipoprotein (LDL). Results Exercise produced a significant reduction in BMI (−1.01 kg/m2, 95% CI −2.00 to −0.01) and WC (−3.09 cm, 95% CI −4.14 to −2.04) but not LDL cholesterol (−0.31 mg/dL, 95% CI −0.81 to 0.19). Analyses revealed substantial heterogeneity likely due to the type and intensity of exercise. Data on adverse effects were minimal. The overall level of evidence is moderate due to imprecision and heterogeneity. Conclusions Exercise in overweight and obese older individuals improves anthropometric measures such as BMI and WC. The effect of exercise on serum lipids is unclear.
Hydroxycruciforms: Amine-responsive fluorophores

The synthesis of three hydroxy-substituted cruciforms (XF, 1,4-bis(4'-hydroxystyryl)-2,5-bis(4''-methoxyphenylethynyl)benzene, 1,4-bis(4'-methoxystyryl)-2,5-bis(4''-hydroxyphenylethynyl)benzene, and 1,4-bis(4'-hydroxystyryl)-2,5-bis(4''-hydroxyphenylethynyl)benzene) starts with a Horner reaction followed by a Sonogashira coupling and subsequent deprotection. The three herein described XFs contain either two or four free phenolic hydroxyl groups. All three XFs were subjected to photometric UV/Vis titrations in a methanol/water mixture. The respective pK(a) values were obtained by data deconvolution. As the three XFs display a significant change in emission color upon photoinduced deprotonation, the XFs were taken up in different solvents and exposed to twelve amines. The amine-dependent change in emissivity of the tetrahydroxy XF is sufficiently distinct in the eight solvents that all of the inspected amines are discerned by a linear discriminant analysis. The tetrahydroxy XF in different solvents forms a sensor array, the response of which is based on the excited-state proton transfer (ESPT) to amines and mediated by the choice of the battery of solvents that are utilized.