cssi/SciSciGPT-SciSciNet huggingface dataset:
Influence of the Shape of Nanostructured Metal Surfaces on Adsorption of Single Peptide Molecules in Aqueous Solution

Self-assembly and function of biologically modified metal nanostructures depend on surface-selective adsorption; however, the influence of the shape of metal surfaces on peptide adsorption mechanisms has been poorly understood. The adsorption of single peptide molecules in aqueous solution (Tyr(12) , Ser(12) , A3, Flg-Na(3) ) is investigated on even {111} surfaces, stepped surfaces, and a 2 nm cuboctahedral nanoparticle of gold using molecular dynamics simulation with the CHARMM-METAL force field. Strong and selective adsorption is found on even surfaces and the inner edges of stepped surfaces (-20 to -60 kcal/mol peptide) in contrast to weaker and less selective adsorption on small nanoparticles (-15 to -25 kcal/mol peptide). Binding and selectivity appear to be controlled by the size of surface features and the extent of co-ordination of epitaxial sites by polarizable atoms (N, O, C) along the peptide chain. The adsorption energy of a single peptide equals a fraction of the sum of the adsorption energies of individual amino acids that is characteristic of surface shape, epitaxial pattern, and conformation constraints (often β-strand and random coil). The proposed adsorption mechanism is supported and critically evaluated by earlier sequence data from phage display, dissociation constants of small proteins as a function of nanoparticle size, and observed shapes of peptide-stabilized nanoparticles. Understanding the interaction of single peptides with shaped metal surfaces is a key step towards control over self-organization of multiple peptides on shaped metal surfaces and the assembly of superstructures from nanostructures.
Constraints on the Applicability of an Interface Dynamo to the Sun

Taking into account the helioseismically inferred interior structure, we show that a pure interface-type dynamo does not work for the Sun if the skin effect for poloidal fields does not allow them to penetrate the tachocline. Using a simple mean-field kinematic α-Ω dynamo model, we demonstrate that, in the absence of tachocline radial shear participating in the dynamo process, a latitudinal differential rotation can provide the necessary Ω-effect to drive an oscillation in an interface dynamo, but it alone cannot produce the latitudinal migration. We show that to make an interface dynamo work with the constraints of interior structure and skin depth, a meridional circulation is essential. We conclude that a flux-transport dynamo driven by both the Babcock-Leighton and interface/bottom α-effects is a robust large-scale dynamo for the Sun.
Phytoremediation-by-design: community-scale landscape systems design for healthy communities

Since the Industrial Revolution humans have introduced hazardous compounds into the environment. Interest has grown for combining urban planning/design processes with phytoremediation as a systems-based approach to environmental remediation. Phytoremediation has potential to transform traditional urban infrastructure processes thereby enhancing the formative structure of the urban context. A historic view of integrating ecosystems within urban planning and design processes is provided, and an ecologically based approach to creating urban contexts through environmentally responsive community planning and design is proposed. Evidence supports incorporating phytoremediation into the community-wide urban planning and design process to establish and sustain communities, environment, human health, and prosperity. Conclusions are drawn from historic and emerging urban planning and design theories, practices, and present and past successes in creating environmentally responsive sustainable communities. Conclusion...
Two-point halogen bonding between 3,6-dihalopyromellitic diimides

The syntheses of 3,6-dichloro-, -dibromo-, and -diiodopyromellitic diimides—ACl, ABr, and AI, respectively—have been achieved. X-Ray crystallography of single crystals of ACl and ABr unveils the formation of extensive halogen-bonding networks in the solid state as a consequence of interactions between the lone pairs on the carbonyl oxygen atoms with the σ-holes of the halogen atoms. Further, the solid-state superstructure of diiodopyromellitic diimide is characterised by the formation of associated halogen-π dimers. The co-crystallisation of ACl or ABr with a 1,5-diaminonaphthalene derivative DN yields co-crystals of a mixed-stack charge-transfer (CT) complex which are supported by an expansive hydrogen-bonded network in addition to halogen-bonded belts that bring adjacent mixed-stacks into association with each other. 2,6-Dimethoxynaphthalene (DO) proved to be an effective CT complement to AI, yielding solvent-free co-crystals with superstructures which are comprised of a 1:2 ratio of AI to DO. This dimeric halogen-bonding motif is reminiscent of the formation of hydrogen-bonded dimers between carboxylic acids.
The Culture of Claviceps purpurea. I. Growth and Nutrition in Submerged Culture

Claviceps purpurea was found to be capable of prolific mycelial development in submerged culture. Of the numerous carbon and nitrogen sources investigated, it was found that mannitol (2 per cent) and casein hydrolysate (1 per cent) incorporated in a basic nutrient solution allowed maximum production of mycelium. An average yield of 1.48 Gm. of dry weight of growth per 100 ml. of medium in a period of seven days following minimum inoculation was obtained. A correlation between growth and change in the hydrogen ion concentration of the culture medium was observed. It appears possible to predict the optimal fermentation time in any medium by a determination of pH. Strain variation of the organism has been emphasized as an important factor in the submerged culture of C. purpurea.
In vivo footprinting reveals unique cis-elements and different modes of hypoxic induction in maize Adh1 and Adh2.

The transcriptional activation of maize alcohol dehydrogenase-1 (Adhl ) and alcohol dehydrogenase-2 (Adh2) is accompanied by changes in the chromatin structure within the 5’-flanking region of each gene. The positions of DNA-binding factors bound to the 5‘-flanking regions were determined by in vivo dimethyl sulfate footprinting of maize suspension cultures over 8 hours of hypoxic induction. In Adhl there are two types of DNA-binding factors associated with the promoter region. One set of factors is constitutively associated with the cis-regulatory anaerobic response element, whereas two additional factors bind only after Adhl has been induced by hypoxic stress. Returning hypoxically stressed cells to an aerobic environment restores the dimethyl sulfate footprint observed for the uninduced Adhl gene. In contrast, all of the factors bound to the 5‘-flanking region of Adh2 are constitutively present and unchanged by hypoxia. There is one footprint site common to both Adhl and Adh2, but it is not an anaerobic response-like element.
Parasitism and soft-bottom community structure: studies in a polychaete-amphipod system

Impacts of the trematode parasite Zoogonus rubellus on individuals of its host, the infaunal sandworm Nereis virens, were explored to assess influences that parasites might have on the structure of soft-bottom infaunal communities. Parasites were common in sandworms collected from a mudflat in Maine, with prevalence reaching 100% for large, commercial-sized sandworms and intensities of infection often exceeding 100 metacercariae per host. Parasitism was determined to be costly as sandworms exposed to parasites in the laboratory had higher mortality and foraged less on a main prey item, the amphipod Corophium volutator, than unexposed controls. As Nereis and Corophium are key intermediate-level members in infaunal communities, it is argued that parasitism of sandworms might directly and indirectly influence the structure of soft-bottom communities.
Estrogen Replacement Therapy in Breast Cancer Survivors: A Time for Change

POSTMENOPAUSAL women often experience annoying and sometimes debilitating menopausal symptoms, and breast cancer survivors are no exception. Hot flashes, dyspareunia, atrophic vaginitis with attendant urinary tract symptoms, sleep disturbance, and mood change are among these symptoms. Coronary artery disease and osteoporosis may be more insidious, but potentially fatal consequences of menopausal estrogen decline. Estrogen replacement therapy (ERT) has been shown to ameliorate these problems,1,2and as informed consumers, breast cancer survivors are increasingly inquiring about and/or requesting ERT.3 There are more breast cancer survivors alive now than ever before, so their nononcologic health problems are a growing concern. A dramatic rise in the incidence rates of breast cancer occurred in the United States between 1982 and 1987, presumably because of increased screening.4The incidence of noninvasive and of small, invasive, axillary nodenegative breast cancers rose concurrently.4Five-year survival rates for breast cancer patients also have been
Moving contact lines and rivulet instabilities. Part 1. The static rivulet

A rivulet is a narrow stream of liquid located on a solid surface and sharing a curved interface with the surrounding gas. Capillary instabilities are investigated by a linearized stability theory. The formulation is for small, static rivulets whose contact (common or three-phase) lines (i) are fixed, (ii) move but have fixed contact angles or (iii) move but have contact angles smooth functions of contact-line speeds. The linearized stability equations are converted to a disturbance kinetic-energy balance showing that the disturbance response exactly satisfies a damped linear harmonic-oscillator equation. The ‘damping coefficient’ contains the bulk viscous dissipation, the effect of slip along the solid and all dynamic effects that arise in contact-line condition (iii). The ‘spring constant’, whose sign determines stability or instability in the system, incorporates the interfacial area changes and is identical in cases (ii) and (iii). Thus, for small disturbances changes in contact angle with contact-line speed constitute a purely dissipative process. All the above results are independent of slip model at the liquid–solid interface as long as a certain integral inequality holds. Finally, sufficient conditions for stability are obtained in all cases (i), (ii) and (iii).
Computer-related posture and musculoskeletal discomfort in middle school students

In recent years, there has been an increasing concern over the association between computer use and reports of discomfort, aches and pains in students. It is suggested that the physical set-up and individual styles of using interactive media has an influence over this discomfort. As children grow up, they will interact and use computers throughout most of their life. Healthy computing may be vital to preventing/reducing the incidence of discomfort/pain associated with interactive media. This research paper will describe a study, which has collected health and comfort data on the incidence and prevalence of self-reported computer-related musculoskeletal discomfort/pain among 6th and 7th grade students in three middle schools in New England. General base line data from this three-year study is reported.
Crystal Growth in the System PbO-B2O3

The temperature dependence of the rate of growth of PbO/2B2O3 from lead borate melts with PbO/B2O3 mole ratios of 1/3,1/2, 2/3, and 1 was determined. The maximum growth rates occurred from those melts which contained a slight excess of PbO. The results are explained on the basis of a modification in the structure of the melt in the interfacial zone as the PbO content is changed. Such changes markedly affect the fluidity of the melt, alter the concentration of crystallizable species, and may reduce the driving force for crystallization.
Late administration of murine CTLA-4 blockade prolongs CD8-mediated anti-tumor effects following stimulatory cancer immunotherapy

We have demonstrated that immunostimulatory therapies such as interleukin-2 (IL-2) and anti-CD40 (αCD40) can be combined to deliver synergistic anti-tumor effects. While this strategy has shown success, efficacy varies depending on a number of factors including tumor type and severe toxicities can be seen. We sought to determine whether blockade of negative regulators such as cytotoxic T lymphocyte antigen-4 (CTLA-4) could simultaneously prolong CD8+ T cell responses and augment T cell anti-tumor effects. We devised a regimen in which anti-CTLA-4 was administered late so as to delay contraction and minimize toxicities. This late administration both enhanced and prolonged CD8 T cell activation without the need for additional IL-2. The quality of the T cell response was improved with increased frequency of effector/effector memory phenotype cells along with improved lytic ability and bystander expansion. This enhanced CD8 response translated to improved anti-tumor responses both at the primary and metastatic sites. Importantly, toxicities were not exacerbated with combination. This study provides a platform for rational design of immunotherapy combinations to maximize anti-tumor immunity while minimizing toxicities.
A study of academic performance by immigrant generation with an emphasis on the black immigrant experience

Purpose – Instead of identifying them as a single monolithic group, the purpose of this paper is to evaluate whether the academic performance of black immigrants differs from African Americans as well as Asian and Hispanic students of comparable immigrant generation. By identifying how well black immigrant students perform on standardized tests, grade point averages (GPA) and college enrollment, this study proposes a more comprehensive look into this growing immigrant group. Design/methodology/approach – The research uses a data from the Educational Longitudinal Survey of high school sophomores conducted by the National Center for Education Statistics. Data used in this study are from the baseline survey in 2002 and the second follow-up in 2006 when most students had graduated from high school. The methodology includes OLS, binary and ordered logistic regression models. Findings – The study finds that while second-generation blacks outperform the native-born generation on standardized tests, this does not...
Generalized temperature measurement equations for Rhodamine B dye solution and its application to microfluidics.

Temperature mapping based on fluorescent signal intensity ratios is a widely used noncontact approach for investigating temperature distributions in various systems. This noninvasive method is especially useful for applications, such as microfluidics, where accurate temperature measurements are difficult with conventional physical probes. However, the application of a calibration equation to relate fluorescence intensity ratio to temperature is not straightforward when the reference temperature in a given application is different than the one used to derive the calibration equation. In this report, we develop and validate generalized calibration equations that can be applied for any value of reference temperature. Our analysis shows that a simple linear correction for a 40 °C reference temperature produces errors in measured temperatures between −3 to 8 °C for three previously published sets of cubic calibration equations. On the other hand, corrections based on an exact solution of these equations restri...
Abstract 50: Abrogation of stromal TGF-β signaling induces DNA damage and genetic/epigenetic alterations in neighboring epithelia

Inactivation of tumor suppressor genes in stromal fibroblast induces epithelial cancer development, suggesting an important role of stroma in epithelial homoeostasis. We investigated the underlying mechanisms in squamous cell carcinoma (SCC) development due to loss of TGF- signaling in FSP1+ fibroblasts (Tgfbr2 fspKO ). We found that stroma specific deletion of Tgfbr2 resulted a loss of p15 and p16, the cyclin dependent kinase (CDK) inhibitors in adjacent epithelia. In addition, there was an increased p21 methylation in the promoter region of the p53 binding site. These data suggest that multiple cell cycle checkpoints were compromised in the epithelia of Tgfbr2 fspKO mice. Consistent with these observations, there was an increased cell proliferation in the epithelial compartment. The mechanisms mediating the cross talk between the epithelia and the stroma apparently involved inflammation that occurred only in the Tgfbr2 fspKO mice but not in Tgfbr2 flox/flox mice. This is characterized by an increased CD45+ leukocyte infiltration, increased cytokines expression (IL-10, IFN-γ TNF-α and GM-CSF) and elevated levels of iNOS, COX2 and NFκB. Interestingly, a significant DNA damage, featured by 8-Oxo-dG DNA adduct formation, and elevated expression of γ-H2AX, a histone protein in response to DNA double strand break, was observed in Tgfbr2 fspKO mice. Inhibition of inflammation with COX2 inhibitor (Celecoxib) or germ free housing condition, significantly delayed epithelial hyperplasia/dysplasia and reduced DNA damage in Tgfbr2 fspKO mice. Examination of human esophageal cancers showed a downregulation of TβR2 in the stromal fibroblast, and an increased inflammation and DNA damage similar to Tgfbr2 fspKO mice. Together, our data demonstrate that attenuation of stromal TGF- signaling induces inflammation that in turn causes DNA damage, epigenetic and genetic alterations in epithelia. Therefore, therapeutic targeting of inflammation and tumor microenvironment may be useful in treating cancers with downregulation of TGF- signaling in stroma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 50. doi:1538-7445.AM2012-50
Role of ECM in the pathogenesis of diabetic retinopathy and POAG

D retinopathy and glaucoma are major ocular diseases that cause significant vision loss and subsequent blindness. However, the precise mechanisms involved in the onset and the progression of these diseases are still not completely understood. While clinical reports have indicated a higher incidence of diabetic retinopathy and glaucoma in the diabetic population compared to the general population, it is unclear whether an association exists between these two disease processes. The extracellular matrix (ECM) is an important determinant of functional properties for retinal blood vessels and trabecular meshwork (TMW). Since retinal blood vessels and TMW are major targets of diabetes, studies have focused on understanding how hyperglycemia affects these tissues. While increased ECM deposition in the outflow pathway may cause resistance to aqueous outflow and contribute to the development of primary open angle glaucoma (POAG), increased ECM can compromise vascular function in the retina. This presentation will focus on understanding a common pathological link between the two ocular diseases, in particular, how overexpression of ECM may contribute to the development of diabetic retinopathy and POAG.
Reduced Order Modeling Applied to Reactive Flow Control

Active flow control involves mechanically adding or removing or otherwise altering the balance of flow field energy to reach a desired flow state. If this technology were to be utilized in conjunction with closed-loop control technologies, it is conceivable that a flow field could be controlled reactively; that is the present state of the flow field could be sensed and altered to achieve a more desirable state. To achieve this end goal, a robust means of modeling flow field behavior is highly desirable. This paper discusses using proper orthogonal decomposition as a modeling method for low-Reynoldsnumber flow about a circular cylindar.
The effect of stretching on recovery of muscular fatigue by electromyographic analysis

健常女性6名の腓腹筋を対象に筋疲労回復におけるストレッチングの効果を筋電図周波数解析により検討した。つま先立ちを疲労困憊まで行なわせた後にストレッチングを30秒間行ない、安静とストレッチングの筋疲労の回復効果を比較した。その結果、安静とストレッチングの疲労回復率に有意な差はなかった。この結果より、運動後の筋疲労の回復において筋の伝導速度の回復に関してはストレッチングの効果はないと考えられ、他の因子すなわち輿奮収縮連関や運動終板などが関わっていると考えられた。
Effect of altered acid-base balance and of various agonists on levels of renal glutamate dehydrogenase mRNA.

Rat kidney contains 3.5-kb and 2.8-kb mRNAs that encode for glutamate dehydrogenase (GDH). The levels of both mRNAs are increased gradually after onset of chronic metabolic acidosis and reach a max...
Evaluation of the meiotic spindle apparatus in oocytes undergoing intracytoplasmic sperm injection

Objective To determine whether intracytoplasmic sperm injection has an adverse effect on the meiotic spindle of oocytes after injection of a sperm into the ooplasm. Design Hamster oocytes were injected with human sperm (Test group) and evaluated for meiotic spindle and chromosome morphology using immunofluorescent staining. Results were compared with control uninjected oocytes exposed to the microscope environment (CS group) and untreated oocytes remaining in the incubator (CI group). Setting Basic research center at a medical school. Results No significant differences were noted in spindle appearance and chromosome alignment between Test (13 abnormal/68 normal) and both control groups (CS 9/73 and CI 12/71; P = 0.602). Conclusion Our results demonstrate that injection of human sperm into the cytoplasm of hamster oocytes may not result in a significant increase in damage to the meiotic spindle provided care is taken to orient the polar body away from the site of injection.
Hemodynamic characteristics of critical stenosis in canine coronary arteries.

To determine the hemodynamic characteristics of critical stenosis of coronary arteries, mean left circumflex coronary artery (LCCA) flow, myocardial peak reactive hyperemic response (PRHR), myocardial P o 2 and P co 2 electrocardiograms, and aortic pressure were monitored at precise degrees of LCCA stenosis in 18 dogs. Stepwise LCCA constriction by a specially designed occluder resulted in a gradual drop in PRHR but little change in other variables. When PRHR was reduced 96 per cent, critical stenosis was achieved, and further constriction caused pronounced and sudden changes in all parameters. When critical stenosis occurred, LCCA diameter had been reduced by 74 ± 2 per cent. Mean LCCA flow was reduced from a base-line level of 42 ± 2 to 34 ± 2 c.c. per minute. P o 2 in the myocardium was reduced from 24 ± 1.5 to 16 ± 1.6 mm. Hg. P co 2 increased from 43 ± 5 to 55 - 5 mm. Hg. T waves in Lead 11 became isoelectric. The myocardium was well perfused and able to regulate flow through an artery narrowed up to 74 per cent. Beyond this point of critical stenosis, the vascular bed was maximally dilated and further narrowing caused ischemia. These findings indicate that PRHR may be useful at operation to determine whether all significant lesions are bypassed and whether graft flow is adequate.
Constitutive activation of a phosphoinositidase C-linked G protein in murine fibroblasts decreases agonist-stimulated Ca2+ mobilization

We compared Ca2+ signaling and inositol polyphosphate metabolism in NIH-3T3 cells stably transfected with cDNA encoding either the wild-type G protein G16 alpha subunit or a GTPase-deficient alpha 16 subunit (Q212L-alpha 16). Constitutive activation of phosphoinositidase C (PIC) in cells expressing Q212L-alpha 16 was demonstrated by 1) an increased basal level of [3H]inositol polyphosphates, 2) an enhanced rate of [3H]inositol polyphosphate accumulation in cells treated with 10 mM LiCl, and 3) an increased rate of incorporation of [3H]inositol into cell lipids. Q212L-alpha 16 cells had a diminished cell growth rate. Basal intracellular Ca2+ concentration was equivalent in Fura-2 acetoxymethyl ester-loaded Q212L-alpha 16 cells compared with controls; however, calcium release in Q212L-alpha 16 cells exposed to ionomycin, ATP (a G protein-linked agonist), or platelet-derived growth factor (a tyrosine kinase-linked agonist) was decreased. Permeabilized, 45Ca-loaded Q212L-alpha 16 cells released less 45Ca at each concentration of inositol-1,4,5-trisphosphate than did control cells. Accordingly, the total amount of inositol trisphosphate (IP3) receptor protein was decreased in Q212L-alpha 16 cells relative to controls. These data demonstrate that Q212L-alpha 16 cells maintain physiological levels of cytoplasmic calcium and partially loaded Ca2+ stores in the face of constitutively active PIC. This is accomplished, at least in part, by down-regulation of IP3 receptor number. Thus, diminution in cell growth rate in Q212L-alpha 16 cells seems to be attributable to a combination of at least two effects: a direct effect of PIC activation leading to partial depletion of Ca2+ stores and an indirect, adaptive response resulting in a decreased IP3 receptor number.
AIDS research in developing countries: do the ends justify the means?

Abstract Concrete ethical standards for human research are clearly stipulated in both international and national codes of ethics, and are meant to protect human subjects, especially the most vulnerable. A recent clinical study conducted from 1994 to 1997 by Dr. Thomas C, Quinn, M.D. has fueled the debate raging in the scientific community regarding the ethics of clinical AIDS research in developing countries. Quinn's conducted a community-based, randomized, controlled study of 15,127 rural Ugandans to determine whether intermittent antibiotic treatment to reduce the prevalence of other sexually transmitted diseases would also reduce the rate of HIV transmission. Subsequently, the study identified 415 couples in which one partner was HIV positive and one was initially HIV negative and followed them prospectively for up to 30 months. Researchers were not permitted to inform the seronegative partner of the HIV status of the other partner. As a result, 90 of the initially HIV negative partners (21.7%) seroconverted during a follow-up period of 30 months. To allow for research studies in developing countries that are not permitted in the United States appears to make the Third World equivalent to a 'research sweat shop'. Developing nations offer easy access to patients, reduced costs, and less stringent regulations. This appears to create a double standard for medical research that is both ethically and humanly unacceptable, especially when other viable option exist. To allow relativism to seep into the international and national ethical standards will open the door to an idea that condones the possible abuse of those least able to protect themselves. Researchers have an ethical responsibility to uphold the integrity of these ethical standards. Failure to do so today may have a devastating impact on humanity in the future.
Participatory Video in the Framework of Adult Education

I introduce the participatory video projects discussed in the remainder of this book in the framework of adult education and then examine one of the projects drawing on a visual analysis. The analysis indicates that the project enabled the participants to voice themselves on critical social issues. While it upholds the potential of participatory video to promote participatory culture among adult learners, I also bear witness to some challenges. I critically reflect on them to explore ways to foster the potential.
CHAPTER 16 – Carbohydrate Metabolism III: Glycoproteins, Glycolipids, GPI Anchors, Proteoglycans, and Peptidoglycans

Glycoproteins can be classified into two major types with differing biosynthetic pathways. The first is the asparagine-linked glycoproteins (N-glycans) , which contain an N-glycosidic linkage between N-acetylglucosamine and the β-amide nitrogen of an asparagine residue in the protein (GlcNAc-N-Asn). This type of linkage predominates in serum glycoproteins. The second is the serine (threonine)-linked glycoprotein (O-glycans) , such as salivary mucin and a number of other proteins and proteoglycans, which contain an O-glycosidic linkage between the hydroxyl groups of serine or threonine and N-acetylgalactosamine. The glycosphingolipids (GSLs, glycolipids) include neutral glycosphingolipids, gangliosides, and sulfatoglycosphingolipids. All glycosphingolipids contain an oligosaccharide chain of one or more residues of galactose, glucose, N-acetylglucosamine, N-acetylgalactosamine, or fucose. Glycosaminoglycans (GAGs; mucopolysaccharides) are long, highly negatively charged, unbranched polymers of repeating disaccharide units. They are classified according to the hexosamine units that alternate with uronic acid in the polymer. GAGs are present in most cells and tissues, but are most often associated with connective tissue and extracellular matrix. Most GAGs are a part of a larger molecule called a proteoglycan. GAGs are attached to the core protein of proteoglycans through an oligosaccharide link region of gal-gal-xyl-Ser. Various proteoglycans and glycosaminoglycans are found in the extracellular matrix including hyaluronic acid, proteochondroitin/dermatan sulfate, and proteoheparan sulfate. In addition to the role of proteoglycan and GAGs as highly solvated structural molecules, they have now been identified as important mediators of receptor function and may also have a role in normal morphology and malignancies.
Bone up: craniomandibular development and hard-tissue biomineralization in neonate mice.

Abstract The presence of regional variation in the osteogenic abilities of cranial bones underscores the fact that the mechanobiology of the mammalian skull is more complex than previously recognized. However, the relationship between patterns of cranial bone formation and biomineralization remains incompletely understood. In four strains of mice, micro-computed tomography was used to measure tissue mineral density during perinatal development in three skull regions (calvarium, basicranium, mandible) noted for variation in loading environment, embryological origin, and ossification mode. Biomineralization levels increased during perinatal ontogeny in the mandible and calvarium, but did not increase in the basicranium. Tissue mineral density levels also varied intracranially, with density in the mandible being highest, in the basicranium intermediate, and in the calvarium lowest. Perinatal increases in, and elevated levels of, mandibular biomineralization appear related to the impending postweaning need to resist elevated masticatory stresses. Similarly, perinatal increases in calvarial biomineralization may be linked to ongoing brain expansion, which is known to stimulate sutural bone formation in this region. The lack of perinatal increase in basicranial biomineralization could be a result of earlier developmental maturity in the cranial base relative to other skull regions due to its role in supporting the brain’s mass throughout ontogeny. These results suggest that biomineralization levels and age-related trajectories throughout the skull are influenced by the functional environment and ontogenetic processes affecting each region, e.g., onset of masticatory loads in the mandible, whereas variation in embryology and ossification mode may only have secondary effects on patterns of biomineralization. Knowledge of perinatal variation in tissue mineral density, and of normal cranial bone formation early in development, may benefit clinical therapies aiming to correct developmental defects and traumatic injuries in the skull, and more generally characterize loading environments and skeletal adaptations in mammals by highlighting the need for multi-level analyses for evaluating functional performance of cranial bone.
Rapid variability of gamma-ray blazars: a model for MKN 421

Abstract The extremely rapid burst of TeV photons from MKN421 (1996 May 15), with a doubling time of 20 minutes at TeV energies, can be reconciled with the standard properties of a gamma-ray jet (bulk factor Γ around 10 and size around 1017 cm) if one relates the variability to anisotropies in the comoving frame of the jet, associated with the geometry of the shocks. The electrons are accelerated in conical shocks with both opening and viewing angle around 1 Γ . If the injection time and the cooling time are much less than the crossing time of the photons, it is possible to observe very short flares in the light curve, in satisfactory agreement with the observations. The geometric condition on the viewing angle is not especially severe, and the probability to observe fast variability is around 20%.
High-resolution Direction-of-Arrival estimation in SNR and snapshot challenged scenarios using multi-frequency coprime arrays

This paper proposes two high-resolution Direction-of-Arrival (DOA) estimators using coprime sensor arrays (CSA) processing broadband signals. The product processor estimates the broadband spatial power spectral density (PSD) by averaging narrowband spatial PSD estimates. These narrowband PSD estimates are formed by multiplying one CSA subarray scanned response with the complex conjugate of the other. Contrastingly, the min processor estimates the broadband spatial PSD by taking the minimum over all subarray periodograms at all processed frequencies for each bearing. The inverse Fourier transform of the broadband spatial PSD estimates the spatial correlation function, which populates the diagonals of a Toeplitz augmented covariance matrix (ACM). The MUSIC algorithm estimates the source DOAs from this constructed ACM. Combining the CSA narrowband PSD estimates over additional bandwidth reduces the number of snapshots needed to attenuate cross-terms in the spatial PSD estimates, providing processing gains for DOA estimation. The MUSIC pseudo-spectra suggest that the product algorithm performs better in scenarios with more sources than sensors and the min algorithm performs better in scenarios with varying source power levels. Monte Carlo simulations show that the new DOA estimators achieve improved precision over previous broadband CSA DOA estimators in snapshot-challenged scenarios.
Chd7 deficiency delays leukemogenesis in mice induced by Cbfb-MYH11 .

Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. Previous studies showed that the interaction between CBFβ-smooth muscle myosin heavy chain (SMMHC; encoded by CBFB-MYH11) and RUNX1 plays a critical role in the pathogenesis of this leukemia. Recently, it was shown that chromodomain helicase DNA-binding protein-7 (CHD7) interacts with RUNX1 and suppresses RUNX1-induced expansion of hematopoietic stem and progenitor cells. These results suggest that CHD7 is also critical for CBFB-MYH11-induced leukemogenesis. To test this hypothesis, we generated Chd7f/fMx1-CreCbfb+/56M mice, which expressed the Cbfb-MYH11 fusion gene and deactivated Chd7 in hematopoietic cells upon inducing Cre with polyinosinic-polycytidylic acid. The Lin-Sca1-c-Kit+ (LK) population was significantly lower in Chd7f/fMx1-CreCbfb+/56M mice than in Mx1-CreCbfb+/56M mice. In addition, there were fewer 5-bromo-2'-deoxyuridine-positive cells in the LK population in Chd7f/fMx1-CreCbfb+/56M mice, and genes associated with cell cycle, cell growth, and proliferation were differentially expressed between Chd7f/fMx1-CreCbfb+/56M and Mx1-CreCbfb+/56M leukemic cells. In vitro studies showed that CHD7 interacted with CBFβ-SMMHC through RUNX1 and that CHD7 enhanced transcriptional activity of RUNX1 and CBFβ-SMMHC on Csf1r, a RUNX1 target gene. Moreover, RNA sequencing of c-Kit+ cells showed that CHD7 functions mostly through altering the expression of RUNX1 target genes. Most importantly, Chd7 deficiency delayed Cbfb-MYH11-induced leukemia in both primary and transplanted mice. These data indicate that Chd7 is important for Cbfb-MYH11-induced leukemogenesis by facilitating RUNX1 regulation of transcription and cellular proliferation.
Reasons for Cigarillo Initiation and Cigarillo Manipulation Methods among Adolescents.

Objective To understand reasons for cigarillo initiation and cigarillo manipulation methods among adolescents. Methods We conducted surveys in 8 Connecticut high schools to assess reasons for trying a cigarillo and cigarillo manipulation methods. We used multivariable logistic regressions to assess associations with demographics and tobacco use status. Results Among ever cigarillo users (N = 697, 33.6% girls, 16.7 years old [SD = 1.14], 62.1% White), top reasons for trying a cigarillo were curiosity (41.9%), appealing flavors (32.9%), because "friends use it" (25.3%), and low cost (22.4%). Overall, 40.3% of ever cigarillo users added marijuana (to create blunts) and 39.2% did not manipulate the product. Endorsement of these reasons for initiation and manipulation methods differed significantly across sex, age, SES and other tobacco use. Conclusions Cigarillo regulations should include restricting all appealing flavors, increasing the cost, monitoring the restriction of sales of cigarillos to minors, and decreasing the appeal of cigarillo manipulation.
Predictors of cardiogenic shock in cardiac surgery patients receiving intra-aortic balloon pumps.

Abstract Background Cardiogenic shock after cardiac surgery leads to severely increased mortality. Intra-aortic balloon pumps may be used during the preoperative period to increase coronary perfusion. The purpose of this study was to characterize predictors of postoperative cardiogenic shock in cardiac surgery patients with and without intra-aortic balloon pumps support. Methods We performed a retrospective analysis of our institutional database of the Society of Thoracic Surgeons for patients operated between January 2008 to July 2015. Multivariable logistic regression was used to model postoperative cardiogenic shock in both the intra-aortic balloon pumps and matched control cohorts. Results Overall, 4,741 cardiac surgery patients were identified during the study period, of whom 192 (4%) received a preoperative intra-aortic balloon pump. Intra-aortic balloon pumps patients had a greater prevalence of diabetes, previous cardiac surgery, congestive heart failure, and an urgent/emergent status (P Conclusion Factors associated with cardiogenic shock among postcardiac surgery patients differ between those patients receiving intra-aortic balloon pumps and those who do not. Further analysis of the effects of prophylactic intra-aortic balloon pumps support is warranted. (Surgery 2017;160:XXX-XXX.)
Borehole Geophysics In Igneous And Metamorphic Rocks

Igneous and metamorphic rocks usually present different petrophysical properties, such as porosity, density, resistivity, and mineralogy, than do sedimentary rocks. For this reason all conventional geophysical logging techniques may not be useful and petrophysics must be used to develop appropriate methods of log analysis. Core analyses plotted against log response and crossplotting of various logs in the computer are particularly useful for identifying the various rock types in an igneous complex. Hydrothermal alteration and fluid movement through fractures are very important parameters that are needed from logs. Hydrothermal alteration may be recognized on well logs through the use of crossplots and borehole gamma spectrometry. The acoustic televiewer supported by other logs has been highly successful for identifying fractures that are transmitting either hot or cold water.
Early Onset Inflammatory Bowel Disease

About 20–30 % of individuals with inflammatory bowel disease (IBD) have symptom onset before 30 years of age and have lifelong disease. Ten to fifteen percent of all IBD patients have an established diagnosis under the age of 18 years. Young children (i.e., under 6 years of age) with IBD represent a unique cohort of patients that is recognized as a valuable group of patients to investigate due to their relative lack of environmental exposures compared with older patients. However, information is sparse regarding the presentation and course of disease in this subset of patients. We therefore present information on both early onset (0–5 years) and later onset (6–18 years) pediatric IBD.
Information Systems Outsourcing Contracts: Theory and Evidence

The information systems outsourcing market has seen rapid growth. Companies are increasingly choosing to outsource many of their information systems activities to services firms rather than sourcing them internally. This trend is inconsistent with the predictions of some of the published literature which point to the high costs of using an outside market. These articles, based on transaction cost economics, point out the difficulty of writing efficient contracts in the face of high transaction costs which result from the considerable technological and business uncertainty in a typical outsourcing arrangement. Yet, the growth in the outsourcing market clearly indicates that the economics of external provision are dominating these contractual concerns. Given that companies are outsourcing information systems services through multi-year contracts, economic theory suggests that outsourcing contracts will seek to minimize the associated transaction costs. I propose a framework for the analysis of information systems outsourcing contracts based on transaction cost theory and the economics of production of information systems services. Based on this framework I develop propositions related to the contractual elements likely to be observed in outsourcing contracts. I test the predictions of the model by studying ten outsourcing contracts in detail. The results indicate that contracts are designed to mitigate transaction costs, and that transaction cost economics is a useful lens with which to analyze an IT services sourcing arrangement.
Nephrogenic diabetes insipidus persisting 57 months after cessation of lithium carbonate therapy: report of a case and review of the literature.

Abstract Objective To illuminate the natural history of prolonged nephrogenic diabetes insipidus after discontinuation of lithium carbonate treatment and to assess the response to therapy with desmopressin acetate and triamterene-hydrochlorothiazide. Methods We analyzed sequential determinations of serum and urine osmolality, plasma arginine vasopressin, serum sodium, blood urea nitrogen, calcium, ionized calcium, parathyroid hormone, and 24-hour urine volume during a period of 57 months in a 67-year-old woman. Results Our patient experienced persistent polyuria in conjunction with having repeated serum osmolalities between 300 and 323 mOsm/kg and urine osmolalities between 130 and 208 mOsm/kg. Concomitant plasma arginine vasopressin levels were as high as 12.0 pg/mL, consistent with the diagnosis of nephrogenic diabetes insipidus. Administration of triamterene-hydrochlorothiazide reduced 24-hour urine volume and serum osmolality while increasing urine osmolality. Desmopressin acetate exhibited no effect. Conclusion In this report, we describe the eighth documented case of persistent nephrogenic diabetes insipidus, lasting 57 months after cessation of lithium therapy, and demonstrate a palliative effect of triamterene-hydrochlorothiazide. (Endocr Pract. 2000;6:324-328)
Abstract 2222: Using rare variants to characterize lung cancer risk

The human genome is exposed to a variety of exogenous and endogenous assaults capable of inducing DNA damage and contributing to diseases like cancer. Multiple DNA repair mechanisms are tasked with identifying and repairing these aberrant nucleotides, but damage is occasionally missed giving rise to somatic mutations. As we age, the relative abundance of somatic mutations increases, which may increase our risk for developing cancer. In addition, inter-individual variation in somatic mutation prevalence suggests an inter-individual variation in (a) inherited DNA repair capacity and/or (b) exposure to environmental mutagens. Therefore, somatic mutation prevalence may serve as an end-point biomarker for cancer risk, as it provides critical information regarding both. While Next Generation Sequencing (NGS) has provided unparalleled access to the human genome and revolutionized the field of cancer genomics, its implementation into the clinical setting has been limited by technical errors introduced during library preparation and on the sequencing platform. This makes identification of rare variants below 10-4 mutations per nucleotide through NGS a challenge, and the use of somatic mutations to characterize cancer risk unfeasible. To address this issue, unique molecular indexes (UMI) were assigned to each genomic copy, enabling reliable identification of rare somatic mutations versus technical errors. We hypothesize that measurement of somatic mutation prevalence in normal bronchial epithelial cells (NBEC) will serve as an end-point biomarker for lung cancer risk by identifying both (a) inherited sub-optimal DNA repair/protection and (b) exposure to inhaled environmental mutagens including components of cigarette smoke, radon, and/or occupational hazards. In our initial pilot study, we used genomic DNA derived from an A549 cell line to optimize an ERCC5 gene-specific, dual-indexed PCR method for UMI assignment, followed by sequencing on the Illumina MiSeq platform. In parallel analyses, UMI correction using 25,000 genomic copies provided over 10-fold greater sensitivity in identifying somatic mutations compared to no UMI correction. Based on this pilot, we obtained three clinical NBEC specimens via cytology brush biopsy of grossly normal (non-cancerous) airway from (a) heavy smoker with lung cancer, (b) heavy smoker without lung cancer, and (c) non-smoking control. UMIs were assigned to 50,000 genomic copies at 16 loci, increasing our theoretical limit of detection to approximately 1 in 4x107 nucleotides. Results thus far support further application of this approach in studies to assess NBEC somatic mutation prevalence as a biomarker for cancer risk. Citation Format: Daniel J. Craig, Mazzin Elsamaloty, Thomas M. Blomquist, Erin L. Crawford, James C. Willey. Using rare variants to characterize lung cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2222.
Impact of Dilute Multiphase Flow in Supersonic Micronozzles

In this study, a computational investigation of multiphase flow within supersonic micronozzles has been performed in an effort to quantify the impact on thrust production and nozzle efficiency. Mot...
Two-Tiered Trademark

Today, we have a two-tiered trademark system. In the top tier, both parties can afford to litigate. In the lower tier, only one party can. This two-tiered system has arisen over the last century because courts refused to follow the law. Faced with trademark law that led to seemingly unjust outcomes in the case before them, courts rewrote trademark law. When those initial rewrites led to different sorts of seeming injustice as cases continued to arise, courts rewrote trademark law again and again. Moreover, judges rewrote trademark law not as part of any systemic and coherent plan for trademark law, but through ad hoc decision-making attempting to achieve what particular judges in particular cases perceived as justice for the particular parties before them. The net result has been a sharp increase in the complexity and uncertainty associated with trademark law, and the expense of resolving trademark disputes. As a result, many entities can no longer afford to participate in the trademark system at all. They can afford neither to defend themselves against overreaching assertions of trademark infringement nor to assert their own trademark rights against even straightforward acts of infringement. For a party who cannot afford the high cost of trademark litigation, when a dispute arises, the party loses. The party loses not because justice or some version of it requires that result. Rather, the party loses because it cannot afford the increasingly high cost of trademark litigation. To remedy this situation, I, like others recently, call for a return to simpler rules in trademark law and to an increased reliance on the registration system as a less expensive means to resolve trademark disputes.
A Tale of Two Patient Safety Programs: Comparing Tools and Skills in Two Programs for Integration into Interprofessional Clinical Simulation-Based Training:

Patient safety improvement efforts across the country intend to address the threat of medical errors that lead to patient morbidity and mortality. Many hospital-based patient safety programs focus ...