cssi/SciSciGPT-SciSciNet huggingface dataset:
Making Sense of Collaboration and Governance: Issues and Challenges

Networks, collaboration, and shared governance are key components of the twenty-first-century research program for public management scholars. This critique examines five key challenges for the field: modeling politics in collaboration, identifying central competencies that government must retain, the "e-limits" to collaboration, creating a multisectoral curriculum, and working with network data.
Heart failure in hypophosphatemic rickets: complications from high-dose phosphate therapy.

ABSTRACT Objective To report a rare case of hypophosphatemic rickets (HR) leading to extensive cardiac complications. Methods We present the clinical course and autopsy findings of a patient with HR, treated with chronic phosphate-only therapy as a child, who subsequently developed tertiary hyperparathyroidism leading to extensive cardiac calcifications and complications. We also review the literature on the pathophysiology of calcifications from HR. Results A 34-year-old man was diagnosed with HR at 4 years of age after presenting with growth delay and leg bowing. Family history was negative for the disease. He was initiated on high-dose phosphate therapy (2-6 g of elemental phosphorus/day) with sporadic calcitriol use between 4-18 years of age. For 6 years he received phosphate-only therapy. Subsequently, he developed nephrocalcinosis, heart valve calcifications, severe calcific coronary artery disease, heart block, and congestive heart failure. At a young age, he required an aortic valve replacement and a biventricular pacemaker that was subsequently upgraded to an implantable cardioverter defibrillator. Autopsy showed extensive endocardial, myocardial, and coronary artery calcifications. Conclusion Cardiac calcification is a known sequela of tertiary hyperparathyroidism when it occurs in patients with renal failure, but it is rarely seen in HR due to high phosphate therapy. Phosphate alone should never be used to treat HR; high doses, even with calcitriol, should be avoided. It is important to be cognizant of high-dose phosphate effects and to consider parathyroidectomy for autonomous function, if needed. This case emphasizes the importance of appropriate therapy, monitoring, and management of patients with HR. (Endocr Pract. 2013;19:e8-e11)
Using Intelligent/Random Library Screening To Design Focused Libraries for the Optimization of Homogeneous Catalysts: Ullmann Ether Formation

A 96-member “pyridine” library consisting of both rationally chosen and “random” members was used to screen Ullmann ether forming reactions. The reaction of 2-bromo-4,6-dimethylaniline and other substrates with a variety of alkoxides was investigated under different conditions with the aid of an automated liquid handler. From the results of the 96-member library screening, a structure activity profile was determined which led to the design of smaller “focused” ligand libraries. The focused libraries produced a higher frequency of hits compared to the original 96-member library. Some of the more effective ligands discovered in this work were found to be generally useful for alkoxylation of a variety of substrates, and also functioned in intramolecular ether forming reactions. This work demonstrates for homogeneous catalysis the analogy to the pharmacological model of drug discovery. By using a large library to screen for a lead compound followed by screening the diversity space closest to the lead, a large...
Metalorganic molecular beam epitaxy of ZnS for flat-panel displays

Thin film luminescent layers have applications in electroluminescent devices and potential application to other displays with high brightness and high resolution requirements. Displays such as field emission devices where high current densities, high electric fields, and small dimensional tolerances are present require phosphors which have high maintenance qualities and good adherence to the face plate. To increase the luminance of EL displays high quality phosphor layers are necessary. In this study, we report the growth kinetics studies of ZnS and the properties of high quality ZnS layers grown by metalorganic molecular beam epitaxial deposition for display applications. The layers' structural and optical properties have been characterized by x-ray diffraction, electron and optical microscopy, and photoluminescence spectroscopy. These measurements were made as a function of the growth and process conditions such as growth temperature, flux ratios, different sulfur precursors, etc. PL spectra exhibited free- and bound-exciton transitions indicative of high quality ZnS material.
N-terminus of the rat adenine glycosylase MYH affects excision rates and processing of MYH-generated abasic sites

Repair of most modified and mispaired bases in the genome is initiated by DNA glycosylases, which bind to their respective targets and cleave the N-glycosyl bond to initiate base excision repair (BER). The mammalian homolog of the Escherichia coli MutY DNA glycosylase (MYH) cleaves adenine residues paired with either oxidized or non-modified guanines. MYH is crucial for the avoidance of mutations resulting from oxidative DNA damage. Multiple N-terminal splice variants of MYH exist in mammalian cells and it is likely that different variants result in the production of enzymes with altered properties. To investigate whether modifications in the N-terminus are consequential to MYH function, we overexpressed intact and N-terminal-deletion rat MYH proteins and examined their activities. We found that deletion of 75 amino acids, which perturbs the catalytic core that is conserved with E.coli MutY, abolished excision activity. In contrast, deletions limited to the extended mammalian N-terminal domain, differentially influenced steady-state excision rates. Notably, deletion of 50 amino acids resulted in an enzyme with a significantly lower K(m) favoring formation of excision products with 3'-OH termini. Our findings suggest that MYH isoforms divergent in the N-terminus influence excision rates and processing of abasic sites.
Hamilton goes empirical: estimation of inclusive fitness from life-history data

Hamilton's theory of kin selection is one of the most important advances in evolutionary biology since Darwin. Central to the kin-selection theory is the concept of inclusive fitness. However, despite the importance of inclusive fitness in evolutionary theory, empirical estimation of inclusive fitness has remained an elusive task. Using the concept of individual fitness, I present a method for estimating inclusive fitness and its components for diploid organisms with age-structured life histories. The method presented here: (i) allows empirical estimation of inclusive fitness from life-history data; (ii) simultaneously considers all components of fitness, including timing and magnitude of reproduction; (iii) is consistent with Hamilton's definition of inclusive fitness; and (iv) adequately addresses shortcomings of existing methods of estimating inclusive fitness. I also demonstrate the application of this new method for testing Hamilton's rule.
Studies on the protein in cat's perilymph and the effect of ultrasound on the protein.

Perilymph samples were collected from normal cats and from cats subjected to ultrasonic irradiation and were analyzed for protein. The control values were between 144.8 mg/100 g and 211.9 mg/100 g with a confidence interval of 95 per cent. Three days after irradiation the protein concentration on the treated side had increased significantly and then, in a week, it declined and the protein values obtained from both sides were similar and greater than the control values. It seemed that both ultrasound and stress produced an increase in permeability to serum proteins and the former caused a greater increase. A few perilymph samples were collected from cases with Meniere's disease. Serum subjected to ultrasound was examined by immunoelectrophoresis. The results were discussed in terms of the effect of ultrasound in the control of Meniere's disease.
Analysis of the secretory phospholipase A2 that mediates prostaglandin production in mast cells

Prostaglandin D2 (PGD2) synthesis in activated mast cells occurs in two phases, an early phase that is dependent on prostaglandin synthase 1 and a delayed phase that is dependent on activation-induced prostaglandin synthase 2 gene expression. Early phase PGD2 synthesis in activated mast cells also requires the activity of a secretory phospholipase A2 (PLA2). It has been thought that the secretory PLA2 expressed in mast cells is group IIa PLA2, encoded by the Pla2 g2a gene. However, activated bone marrow-derived mast cells prepared from Pla2 g2a+/+ mice and mast cells prepared from mice with a mutation in the Pla2 g2a gene both demonstrate early phase PGD2 synthesis. Moreover, mast cells from both murine strains secrete PLA2 activity following activation. Northern and reverse transcriptase/polymerase chain reaction analyses demonstrate that mast cells from Pla2 g2a+/+ and Pla2 g2a-/- mice do not express group IIa PLA2 message. Instead, Northern and reverse transcriptase/polymerase chain reaction analyses demonstrate that both Pla2 g2a+/+ and Pla2 g2a-/- mast cells express mRNA for group V PLA2, encoded by the Pla2gV gene. An antisense oligonucleotide directed against group V PLA2 is also able to inhibit both the early phase of PGD2 production and the secretion of PLA2 activity by activated mast cells. Our data suggest that (i) group IIa PLA2 does not play a significant role in murine mast cell prostaglandin synthesis, (ii) group V PLA2 mediates early mast cell PGD2 production and transcellular PGE2 production in murine mast cells, and (iii) much of the data, based on studies with chemical inhibitors and antibodies, suggesting that group IIa PLA2 is responsible for arachidonic acid mobilization needs to be reevaluated.
The current status of nonoperative management of adult blunt hepatic injuries

This review of 14 recent publications encompassing 495 patients highlights the current role of the nonoperative management of adult blunt hepatic injuries. When careful inclusion criteria were met, the most important of which is hemodynamic stability, a 94% success rate was achieved, clearly attesting to the safety and efficacy of this approach. A 0% liver-related mortality in these 495 patients was achieved, and there were no documented missed enteric injuries. Delayed hemorrhage that led to laparotomy occurred in 2.8% of patients. The mean length of hospital stay was 13 days, and the mean transfusion requirement was 1.9 units of blood per patient. Computed axial tomography scanning was essential and played an integral role in delineating the extent of the injury, identifying other ultra-abdominal injuries that would mandate immediate laparotomy, and following the progress of injury resolution. Overall, 34% of blunt liver injuries were managed nonoperatively. As of 1993, however, available data confirms that 51% of adult reported blunt hepatic injuries have been treated nonoperatively. Rigid adherence to the described guidelines may allow the majority of blunt hepatic injuries to be treated nonoperatively. It should be stressed, however, that this method of patient management should only be undertaken at institutions where the appropriate resources necessary to deal with this patient population are readily available.
Performance and reliability: the ubiquitous challenge

Legend says that Archimedes remarked, on the discovery of the lever, "Give me a place to stand and I can move the world." Today, computing pervades all aspects of society. "Science" and "computational science" have become largely synonymous, and computing is the intellectual lever that opens the pathway to discovery in diverse domains. As new discoveries increasingly lie at the interstices of traditional disciplines, computing is also the enabler for scholarship in the arts, humanities, creative practice and public policy. Equally importantly, computing supports our critical infrastructure, from monetary and communication systems to the electric power grid.With such pervasive dependence, computing system reliability and performance are ever more critical. Although the mean time before failure (MTBF) of commodity hardware components (i.e., processors, disks, memories, power supplies and networks) is high, their use in large, mission critical systems can still lead to systemic failures. Our thesis is that the "two worlds" of software -- distributed systems and sequential/parallel systems -- must meet, embodying ideas from each, if we are to build resilient systems. This talk surveys some of these challenges and presents possible approaches for resilient design, ranging from intelligent hardware monitoring and adaptation, through low-overhead recovery schemes, statistical sampling and differential scheduling and to alternative models of system software, including evolutionary adaptation.
A steady-state exterior Navier-Stokes problem that is not well-posed

We prove that the exterior Navier-Stokes problem with zero velocity at infinity is not well-posed in homogeneous Sobolev spaces. This result complements and clarifies well-known previous results obtained by various authors.
The Role of Uncertainty Quantification for Reactor Physics

The quantification of uncertainties is a crucial step in design. The comparison of a-priori uncertainties with the target accuracies, allows to define needs and priorities for uncertainty reduction. In view of their impact, the uncertainty analysis requires a reliability assessment of the uncertainty data used. The choice of the appropriate approach and the consistency of different approaches are discussed.
Decentralized Controls and Communications for Autonomous Distribution Networks in Smart Grid

The traditional power grid system was constructed in a centralized and radial topology where power is generated and delivered from one end to the other. Conventional methods for unidirectional power flow analysis will no longer be effective to control renewable energy sources implemented at the consumption sector efficiently; new strategies are called for to facilitate the bidirectional flow incurred by power production of the distributed energy resource units. The transformation will require intelligent distribution automation by means of decentralized power management as well as information and communications technologies to actualize smart grid modernization. In this paper, we design autonomous distribution networks that take scalability into account by dividing the legacy distribution network into a set of subnetworks. We tackle the power flow and power balance issues individually in parallel to optimize the global distribution operation by our proposed power-control method. Meanwhile, we propose an overlay multi-tier communications infrastructure for the underlying power network to analyze the traffic of data information and control message required for associated power flow operation. Based on the proposed schemes, we show that we can potentially improve the utilization of renewable energy production and achieve data traffic reduction under decentralized operations as compared to legacy centralized management.
The Role of Lutein in Disease Prevention

Lutein is a non-provitamin-A carotenoid found in dark green, leafy vegetables. Lutein, being fat-soluble, follows the same intestinal absorption path as dietary fat and is affected by the same factors that influence fat absorption. Unlike β-carotene, another major carotenoid in diet and tissue, the bioavailability of lutein appears to be less influenced by food processing. Lutein has been strongly implicated as being protective against age-related macular degeneration (AMD) and cataracts. In the eye, lutein may act as a blue-light filter, protecting the underlying tissues from phototoxic damage. The mechanism by which lutein is involved in the prevention of eye diseases and other diseases, such as breast cancer and cardiovascular heart disease (CHD), may also be related to its role as an antioxidant.
Conduction of the Cardiac Impulse

Depressed excitability and responsiveness were created in excised bundles of canine Purkinje fibers. A segment 8 mm long was depressed by being encased in agar containing 47 mM K+, the ends of the bundle outside the agar remaining normal. Either normal end could be excited through extracellular electrodes. Action potentials were recorded by intracellular microelectrodes at each end and within the depressed segment. Conduction velocity within the depressed segment fell as low as 0.05 m/sec. Abnormalities of impulse transmission through the depressed segment included delay, 2:1 block, higher degrees of block, rate-dependent block, and block showing the Wenckebach phenomenon. Asymmetries of conduction seen included one-way block. Action potentials in the depressed segment were of low amplitude and showed slow upstrokes. Variations in action potential duration occurred in the depressed segment when conduction failed or was very slow and when impulses were dropped. Delay in conduction too great to result simply from a slow upstroke is attributed to summation of excitatory events across regions of block in a syncytium of cells. The results prove that conduction delays great enough to permit re-entry can occur in short segments of Purkinje fibers subjected to high K+.
Insights into the substrate specificity of plant peptide deformylase, an essential enzyme with potential for the development of novel biotechnology applications in agriculture.

The crystal structure of AtPDF1B [Arabidopsis thaliana PDF (peptide deformylase) 1B; EC 3.5.1.88], a plant specific deformylase, has been determined at a resolution of 2.4 {angstrom} (1 {angstrom}=0.1 nm). The overall fold of AtPDF1B is similar to other peptide deformylases that have been reported. Evidence from the crystal structure and gel filtration chromatography indicates that AtPDF1B exists as a symmetric dimer. PDF1B is essential in plants and has a preferred substrate specificity towards the PS II (photosystem II) D1 polypeptide. Comparative analysis of AtPDF1B, AtPDF1A, and the type 1B deformylase from Escherichia coli, identifies a number of differences in substrate binding subsites that might account for variations in sequence preference. A model of the N-terminal five amino acids from the D1 polypeptide bound in the active site of AtPDF1B suggests an influence of Tyr{sup 178} as a structural determinant for polypeptide substrate specificity through hydrogen bonding with Thr{sup 2} in the D1 sequence. Kinetic analyses using a polypeptide mimic of the D1 N-terminus was performed on AtPDF1B mutated at Tyr{sup 178} to alanine, phenylalanine or arginine (equivalent residue in AtPDF1A). The results suggest that, whereas Tyr{sup 178} can influence catalytic activity, other residues contribute to the overall preference for themore » D1 polypeptide.« less
Flow cytometric correlation of the c-myc oncoprotein and cell cycle kinetics of HL60 leukaemia during induced maturation with cytosine arabinoside and dimethylsulphoxide.

Abstract The c-myc oncogene codes for a DNA binding protein that functions in a cell cycle-related manner. A useful model for studying the relationship of c-myc expression with cell cycle kinetics is the HL60 cell line. HL60 cells constitutively express high levels of c-myc mRNA; however, the level can be down-regulated as the cells are induced to differentiate. We have developed a flow cytometric assay for correlating c-myc oncoprotein levels with DNA content. C-myc oncoprotein levels were additionally correlated with c-myc mRNA levels as determined by slot blot hybridization. Dimethylsulphoxide (DMSO) and cytosine arabinoside were used to induce granulocytic and monocytic maturation respectively. Treatment of HL60 cells with DMSO leads to an increase in the per cent of cells in G1/G0 and a decrease in mean c-myc mRNA and oncoprotein levels. The cells with G1 DNA content show the greatest decrease in c-myc protein. ARA-c treatment of HL60 cells leads to a slowing and an accumulation of cells in S phase with a moderate decrease in mean mRNA and only a slight decrease in mean c-myc protein levels. These data support the hypothesis that c-myc is involved in the switch from G1 to G0.
Catalysis by enzyme conformational change as illustrated by orotidine 5′-monophosphate decarboxylase

Abstract An energy decomposition scheme has been used to elucidate the importance of the changes of enzyme conformational substates to the reduction of the activation barrier in enzyme-catalyzed reactions. This analysis may be illustrated by the reaction of orotidine 5′-monophosphate decarboxylase, which exhibits a remarkable rate enhancement of over 17 orders of magnitude compared to the uncatalyzed process. The mechanism shows that the enzyme conformation is more distorted in the reactant state than in the transition state. The energy released from protein conformation relaxation provides the predominant contribution to the rate enhancement of orotidine 5′-monophosphate decarboxylase. The proposed mechanism is consistent with results from site-directed mutagenesis experiments, in which mutations distant from the reactive center can have significant effects on the catalytic rate enhancement (k cat ), but rather a small influence on the binding affinity for the substrate ( K M ).
A Cloud-Evaporation Parameterization for General Circulation Models

Abstract An evaporation-zone (EZ) model for cloud evaporation is developed. In this model a cloud consists of I “cloudlets,” each comprising cloud droplets with radii from zero to rmax, the latter value depending on the drop size distribution (DSD). Evaporation occurs only within the EZ comprised of J ≤ I cloudlets. When the cloudlet at cloud edge evaporates, the EZ progresses one cloudlet into the cloud's interior. This eventually results in evaporation of the cloud in time tE = K(H/h)r2max(1 − Se)−1, where H is the cloud thickness h the EZ thickness, Se the environmental saturation ratio, and K a constant. Values of tE(1 − Se,) versus h are presented for eight observed DSDs. For use in atmospheric general circulation models (GCMs), the cloud evaporation process is represented by dm/dt = −(1 − Se)m/τ, where m is the cloud-water mixing ratio and τ = K(H/h)r2maxn−1. With parameter n chosen sufficiently large, a GCM cloud will evaporate virtually entirely in time tE, for example, 99.3% for n = 5. Values of ...
Location and sequence analysis of a 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase-encoding gene (bpdF) of the biphenyl/ polychlorinated biphenyl degradation pathway in Rhodococcus sp. M5

The 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate (HOPD) hydrolase-encoding gene (bpdF) in the biphenyl (BP)/polychlorinated biphenyl (PCB)-degrading bacterium, Rhodococcus sp. M5 (M5), was found to be located within a 4.5-kb HindIII-BamHI genomic DNA that was 5.4 kb downstream from the bpdC1C2BADE gene cluster. The deduced amino acid (aa) sequence of bpdF revealed that the hydrolase contains 297 aa (32679 Da) that was verified by expression in the Escherichia coli T7 RNA polymerase/promoter system. Unlike previously known HOPD hydrolases, the aa sequence of BpdF appears unique. Interestingly, all HOPD hydrolases and related proteins from the phenol and toluene/xylene degradation pathways, were found to have a bias in the codon usage in the catalytic Ser within the conserved VGNS(M/F)GG motif.
FTY720 Normalizes Hyperglycemia by Stimulating β-Cell in Vivo Regeneration in db/db Mice through Regulation of Cyclin D3 and p57KIP2

Loss of insulin-producing β-cell mass is a hallmark of type 2 diabetes in humans and diabetic db/db mice. Pancreatic β-cells can modulate their mass in response to a variety of physiological and pathophysiological cues. There are currently few effective therapeutic approaches targeting β-cell regeneration although some anti-diabetic drugs may positively affect β-cell mass. Here we show that oral administration of FTY720, a sphingosine 1-phosphate (S1P) receptor modulator, to db/db mice normalizes fasting blood glucose by increasing β-cell mass and blood insulin levels without affecting insulin sensitivity. Fasting blood glucose remained normal in the mice even after the drug was withdrawn after 23 weeks of treatment. The islet area in the pancreases of the FTY720-treated db/db mice was more than 2-fold larger than that of the untreated mice after 6 weeks of treatment. Furthermore, BrdU incorporation assays and Ki67 staining demonstrated cell proliferation in the islets and pancreatic duct areas. Finally, islets from the treated mice exhibited a significant decrease in the level of cyclin-dependent kinase inhibitor p57KIP2 and an increase in the level of cyclin D3 as compared with those of untreated mice, which could be reversed by the inhibition of phosphatidylinositol 3-kinase (PI3K). Our findings reveal a novel network that controls β-cell regeneration in the obesity-diabetes setting by regulating cyclin D3 and p57KIP2 expression through the S1P signaling pathway. Therapeutic strategies targeting this network may promote in vivo regeneration of β-cells in patients and prevent and/or cure type 2 diabetes.
Ethanol enhances erbB-mediated migration of human breast cancer cells in culture.

Growth factor systems (ligands and their receptors) are targets of ethanol toxicity. Inasmuch as alcohol consumption may increase the risk and development of breast cancer, we hypothesize that ethanol enhances cell migration by up-regulating the activities of erbB receptors. Of the three tested breast cancer cell lines that exhibit low invasion capacity (BT-20, MCF-7, and T47D cells), erbB receptors were specifically affected by ethanol only in the T47D cells. Ethanol increased erbB2, erbB3, and erbB4 expression in T47D human breast cancer cells in a concentration-dependent manner. ErbB1 (epidermal growth factor receptor) was unaffected. Heregulin β1 (ligand for erbB3 and erbB4) induced a modest increase in the invasion potential of the T47D cells. Ethanol alone also promoted modest invasion by the T47D cells, however, ethanol dramatically increased their heregulin-mediated invasion. Knocking-out erbB2 with an anti-sense oligonucleotide eliminated heregulin β1-promoted migration and blocked ethanol-induced chemo-migration. Thus, these data suggest that alcohol may enhance metastasis by altering an erbB system, and pivotally, erbB2.
Antimicrobial coating of an N-halamine biocidal monomer on cotton fibers via admicellar polymerization

Abstract The monomer 3-(4′-vinylbenzyl)-5,5-dimethylhydantoin (VBDMH) was synthesized and used to coat cotton fibers by admicellar polymerization using a cationic surfactant. The coated thin-film on cotton was characterized by FTIR and SEM. After chlorination with dilute sodium hypochlorite, the polymeric-coated cotton fabrics effectively inactivated both Staphylococcus aureus and Escherichia coli O157:H7 in relatively brief contact times. The stability and rechargeability of the coated cotton fabrics were very good as evidenced by standard washing tests.
A Viral Movement Protein as a Nuclear Shuttle (The Geminivirus BR1 Movement Protein Contains Domains Essential for Interaction with BL1 and Nuclear Localization)

For the nuclear replicating bipartite geminiviruses such as squash leaf curl to systemically infect the host requires the active participation of two virus-encoded movement proteins, BR1 and BL1. These act in a cooperative manner to transport the viral single-stranded DNA genome from its site of replication in the nucleus to the cell periphery (A.A. Sanderfoot, S.G. Lazarowitz [1995] Plant Cell 7: 1185–1194). We have proposed that BR1 functions as a nuclear shuttle protein, transporting the viral single-stranded DNA to and from the nucleus as a complex that is recognized by BL1 for movement to adjacent cells. To further investigate this, we expressed BR1 mutants known to affect viral infectivity in Spodoptera frugiperda insect cells and Nicotiana tabacum L. cv Xanthi protoplasts and found these to be defective in either their nuclear targeting or their ability to be redirected to the cell periphery when co-expressed with BL1. Translational fusions to [beta]-glucuronidase and alanine-scanning mutagenesis further demonstrated that the C-terminal 86 amino acids of BR1 contains a domain(s) essential for its interaction with BL1 and identified two nuclear localization signals within the N-terminal 113 residues of BR1. These nuclear localization signals were precisely located within distinct 16- and 22-peptide segments of BR1. These studies support and extend our model for squash leaf curl virus movement, showing that BR1 has a domain structure, with an N-terminal region required for nuclear targeting and a C-terminal region required for its interaction with BL1.
Extremal graphs domination insensitive to the removal of k edges

Abstract A connected graph G with order p is defined to be γk-insensitive if the domination number γ(G) is unchanged when an arbitrary set of k edges is removed. The problem of finding the least number of edges in any such graph has been solved for k=1. We determine bounds on this minimum number which are valid for any p and for k ≥ 2.
Publication Bias in Kienböck's Disease: Systematic Review

Purpose Kienbock's disease is considered rare and currently affects fewer than 200,000 people in the United States. Given the inherent challenges associated with researching rare diseases, the intense effort in hand surgery to treat this uncommon disorder may be influenced by publication bias in which positive outcomes are preferentially published. The specific aim of this project was to conduct a systematic review of the literature with the hypothesis that publication bias is present for the treatment of Kienbock's disease. Methods We conducted a systematic review of all available abstracts associated with published manuscripts (English and non-English) and abstracts accepted to the 1992 to 2004 American Society for Surgery of the Hand (ASSH) annual meetings. Data collection included various study characteristics, direction of outcome (positive, neutral/negative), complication rates, mean follow-up time, time to publication, and length of patient enrollment. Results Our study included 175 (124 English, 51 non-English) published manuscripts and 14 abstracts from the 1992 to 2004 annual ASSH meetings. Abstracts from published manuscripts were associated with a 53% positive outcome rate, which is lower than the 74% positive outcome rate found among other surgically treated disorders. Over the past 40 years, studies have become more positive (36% to 68%, p=.007) and are more likely to incorporate statistical analysis testing (0% to 55%, p .999). Conclusions The acceptance rate for negative outcomes studies regarding Kienbock's disease is higher than for other surgical disorders. This may indicate a relative decrease in positive outcome bias among published Kienbock's disease studies compared with other surgical disorders. However, the increasing positive outcome rate for published Kienbock's disease studies over time may suggest a trend of increasing publication bias among journals toward Kienbock's disease studies.
LFA-1 affinity regulation is necessary for the activation and proliferation of naive T cells

The activation of LFA-1 (lymphocyte function-associated antigen) is a critical event for T cell co-stimulation. The mechanism of LFA-1 activation involves both affinity and avidity regulation, but the role of each in T cell activation remains unclear. We have identified antibodies that recognize and block different affinity states of the mouse LFA-1 I-domain. Monoclonal antibody 2D7 preferentially binds to the low affinity conformation, and this specific binding is abolished when LFA-1 is locked in the high affinity conformation. In contrast, M17/4 can bind both the locked high and low affinity forms of LFA-1. Although both 2D7 and M17/4 are blocking antibodies, 2D7 is significantly less potent than M17/4 in blocking LFA-1-mediated adhesion; thus, blocking high affinity LFA-1 is critical for preventing LFA-1-mediated adhesion. Using these reagents, we investigated whether LFA-1 affinity regulation affects T cell activation. We found that blocking high affinity LFA-1 prevents interleukin-2 production and T cell proliferation, demonstrated by TCR cross-linking and antigen-specific stimulation. Furthermore, there is a differential requirement of high affinity LFA-1 in the activation of CD4+ and CD8+ T cells. Although CD4+ T cell activation depends on both high and low affinity LFA-1, only high affinity LFA-1 provides co-stimulation for CD8+ T cell activation. Together, our data demonstrated that the I-domain of LFA-1 changes to the high affinity state in primary T cells, and high affinity LFA-1 is critical for facilitating T cell activation. This implicates LFA-1 activation as a novel regulatory mechanism for the modulation of T cell activation and proliferation.
Dynamic response of plate to moving loads: structural impedance method

Abstract An algorithm based on a structural impedance approach has been developed to study the transient response of plates with arbitrary boundary conditions and subjected to moving loads. Thin plate theory is assumed for the plate model and the algorithm places no restrictions on the loading conditions. The algorithm accounts for the complete dynamic interactions between the moving loads and the plate. Therefore, the method can be applied to the general moving mass problems and to the simplified moving force and static problems. The accuracy of the algorithm is verified by comparing the results obtained from the structural impedance method (SIM), in the case of moving force solutions, with the available exact solutions and with other numerical results. The dynamic deflections obtained from the moving mass solutions are compared with available experimental results. Parametric analyses over a wide spectrum of velocities and mass ratios indicate that the inertial effect on dynamic deflections is pronounced when the vehicle is traveling at high speed.
On wave stability in relativistic cosmic-ray hydrodynamics

Wave stability of a two-fluid hydrodynamical model describing the acceleration of cosmic rays by the first-order Fermi mechanism in relativistic, cosmic-ray-modified shocks is investigated. For a uniform background state, the short- and long-wavelength wave speeds are shown to interlace, thus assuring wave stability in this case. A JWKB analysis is performed to investigate the stability of short-wavelength thermal gas sound waves in the smooth, decelerating supersonic flow upstream of a relativistic, cosmic-ray-modified shock. The stability of the waves is assessed both in terms of the fluid velocity and density perturbations, as well as in terms of the wave action. The stability and interaction of the short-wavelength cosmic-ray coherent mode with the background flow is also studied.
Study on multi-time periods integrated plan of supply chain under uncertain environment

Considering constraints of uncertain customers' demands and uncertain price of raw materials in different time periods of the planning horizon, a problem of multi-time period integrated planning of supply chain under uncertain environment was studied in this paper. According to characteristics of the problem, an optimal stochastic chance constraint programming model with objective of minimum costs was presented, and a real number matrix encoding and stochastic sampling constraints verifying based PSO algorithm was proposed. A numeric example is performed, and the results illustrate the feasibility and the effectiveness of proposed model and algorithm.
A dynamic model of interactions of Ca2+, calmodulin, and catalytic subunits of Ca2+/calmodulin-dependent protein kinase II.

During the acquisition of memories, influx of Ca2+ into the postsynaptic spine through the pores of activated N-methyl-d-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca2+ influx during the first few seconds of activity is interpreted within the Ca2+-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca2+/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca2+ ions. As a first step toward clarifying how the Ca2+-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca2+, calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca2+ play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing of Ca2+ signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca2+ is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca2+ transients arises from the kinetics of interaction of fluctuating Ca2+ with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning.
Macrophage Apolipoprotein Synthesis and Endoneurial Distribution as a Response to Segmental Demyelination

The synthesis and endoneurial distribution of apolipoproteins in response to myelin degradation was elucidated morphologically and biochemically in rodent models of segmental demyelination. At the onset of acute demyelination induced by tellurium (Te) poisoning, macrophages infiltrated the endoneurium and then began to express cytoplasmic immunoreactivity for apolipoprotein E (apo E). When demyelinating nerve slices were incubated with S35-methionine, radiolabeled apo E was released, showing that apo E was actively synthesized by the macrophages. Macrophages secreted apo E into the endoneurial spaces, leading to dense endoneurial accumulations. Other apolipoproteins (apo A1 and albumin) were not synthesized in the endoneurium, but they entered edematous nerves, presumably through an early breakdown in the blood-nerve barrier. During the phagocytosis of myelin, plasma-derived apolipoproteins accumulated within some of the macrophages. In chronic demyelination caused by lead poisoning, the cellular and extracellular distribution of apolipoproteins was similar to Te neuropathy; the amount of apo E accumulation and the macrophage density were proportional to the prevalence of active demyelination in teased fibers. Similar patterns of endoneurial apo E were present in an inherited form of demyelination in the twitcher mouse, after antibody-mediated demyelination, and in demyelination secondary to axonal degeneration. Human sural nerve biopsies had patterns of apolipoprotein E antigenicity that were comparable to the rodent models. We conclude that secretion of apo E by infiltrating macrophages is a generalized response to demyelination, and that endoneurial edema leads to the accumulation of certain plasma apolipoproteins within macrophages. These data suggest that endoneurial apolipoproteins and macrophages might mediate important functions in patients recovering from primary and secondary demyelination.
Neonatal Necrotizing Enterocolitis –Inflammation and Intestinal Immaturity

Neonatal necrotizing enterocolitis is a devastating inflammatory bowel disease of premature infants. The pathogenesis remains incompletely understood and there is no specific treatment. Efforts are ongoing to understand aspects of intestinal immaturity which contribute to susceptibility to this disease. This review focuses on bacterial colonization patterns, intestinal barrier function, and inflammatory responses of immature enterocytes leading to a unique vulnerability of the preterm gut. In addition the possible therapeutic potential of factors in human milk and probiotic bacteria is discussed.
The Analysis of Uncertainty Resolution in Capital Budgeting for new Products

In this paper, a method is developed for analyzing the resolution of uncertainty over time for the individual new product and for combinations of existing and new products, or the firm's over-all product mix. Probability concepts are employed, and it is shown that new products can be evaluated according to their marginal impact upon the resolution of the uncertainty pattern for the firm's total product mix. The analysis of this dimension is undertaken within a capital-budgeting framework, allowing a GO or NO decision to be reached for the new product under consideration. Information about when uncertainty is expected to be resolved enables management to evaluate more realistically the effect of a new-product decision on the riskiness of the firm's entire product mix. This knowledge is valuable in planning for new products and in balancing the firm's risk over time. As a result, more rational capital budgeting for new products is possible.
Monitoring cerebral hemodynamics with transcranial Doppler ultrasound during cognitive and exercise testing in adults following unilateral stroke

An observational study was performed as a preliminary investigation into the use of transcranial Doppler ultrasound (TCD) for recording cerebral hemodynamic changes during multiple tasks. TCD is a method of measuring cerebral blood flow (CBF) using ultrasound transducers in contact with the surface of the head. Using the maximum flow envelope of the Doppler spectrum returning from the middle cerebral artery (MCA), standard clinical flow indices can be calculated and displayed in real time providing information concerning perturbations in CBF and their potential cause. These indices as well as flow velocity measurements have been recognized as useful in measuring changes in responses to various stimulus that can be used to indicate cardiovascular health. For this study, the pulsatility index (PI) and resistivity index (RI) were chosen since they indicate composite changes indicative of vasoconstriction and vasodilatation which are normal hemodynamic responses under appropriate conditions. A total of eleven participants were recruited to take part in this study. Nine of these individuals had no known disability (Controls); two had experienced unilateral cerebrovascular accidents (Strokes) in the ipsilateral MCA distribution. Maximum velocity envelopes of the spectral Doppler data were recorded using a fixation device designed to stabilize two ultrasound probes (2 MHz) to sample the bilateral MCAs CBF. These measures were performed separately while the subject performed four activities: 1) rest, 2) cognitive challenge, 3) cardiovascular exercise, and 4) simultaneous exercise and cognitive challenge. Cardiovascular parameters were calculated from the data by extracting maximum (Vs) and minimum flow velocities (Vd), PI, RI, and time signatures for each cardiac cycle. The data for all participants shows significant changes in cardiovascular parameters between states of rest and exercise, as well as slight trends across time. Although the data are preliminary, they show the capability of using Doppler spectral examination of the bilateral MCAs in individuals with physical limitation performing cardiovascular exercise. The novelty of examining a population using dynamic exercise who before could not perform such exercise offers the opportunity to study the impact of exercise on global cerebral recovery in unilateral stroke with significant physical impairment.
Effectiveness of a new tunneled catheter in preventing catheter malfunction: a comparative study.

Purpose To compare infection and malfunction rates of two different types of antimicrobial-eluting tunneled cuffed catheters (TCCs) for hemodialysis. Materials and Methods The HemoSplit TCC with BioBloc (silver sulfadiazine) coating ( n = 100, control group) and the Tal Palindrome Ruby TCC, which has a novel silver antimicrobial sleeve and a spiral-z tip design ( n = 100, study group), were compared in this case-controlled study. The main endpoints were TCC infection and malfunction. Results Primary-assisted TCC patency was significantly reduced with the BioBloc TCC (71% and 61% at 90 and 180 days, respectively) compared with the Palindrome Ruby TCC (94% at 90 and 180 days, P P P = .002). The infection-free rates of the two TCC types were similar ( P = .36). The reintervention-free rate for infection or malfunction was significantly better with the Palindrome Ruby TCC (76% and 58% at 90 and 180 days, respectively) than with the BioBloc TCC (60% and 45% at 90 and 180 days, respectively; P = .03). Conclusions The results support the use of the Palindrome Ruby TCC on the basis of the significantly lower thrombosis and reintervention rate; randomized trials are justified to confirm this finding and to evaluate its role in the prevention of TCC infection.
Pulmonary mesothelioma in bronchioalveolar lavage: a case report.

Mesothelioma is a neoplasm arising from the mesothelial cells lining the body serosal surfaces. The frequent primary sites include the pleura followed by the peritoneum and rarely the pericardium. Pleural mesothelioma encases the lung and fills the pleural space, which limits the lungs' ability to expand. The initial diagnosis requires the presence of characteristic clinical, radiological, and pathological features. A thorough review of the English language literature found no reports where a diagnosis of mesothelioma was made on material originating from bronchioalveolar lavage (BAL). We report a case of lung parenchymal involvement by mesothelioma shedding cells in BAL specimen. Diagn. Cytopathol. 2008;36:190–192. © 2008 Wiley-Liss, Inc.
Simulator-oriented fault test generator

The problem of generating tests for sequential logic networks has become severe with large-scale integration (LSI). Since the internal gates cannot be tested by direct measurements, it is imperative that a rigorous logic test be developed to ensure quality at the chip level. The sequential complexity of many LSI chips exceeds the practical limitations of the familiar technique of modeling sequential logic for the application of combinational logic test-generation algorithms. Although other approaches, such as pseudo-random pattern generation, have been tried with some success, the pattern count may be quite large. This paper describes a method of test pattern generation that was developed with three objectives: to generate long pattern sequences systematically when needed, to model the sequential logic accurately so that any test generated would be valid, and to focus on assumed faults such as stuck 1 and stuck 0. Also discussed are the strengths and limitations of this method and some comparative results.
Effects of intraperitoneal carbon monoxide on fixed-ratio and screen-test performance in the mouse.

Abstract The behavioral effects of carbon monoxide (CO) administered via IP injection were investigated in the mouse. Mice were trained to lever press under a fixed-ratio (FR) 100 schedule of water reinforcement. Thirty-min test sessions were conducted either immediately or 30 min following IP injections of air (100 ml/kg) or CO (7.5, 15, 30, 50 or 100 ml/kg). CO produced a decrease in rates of responding which was exhibited earlier and lasted longer with increasing doses. Motor performance was also measured with the inverted-screen test following the same doses of CO at either 5, 15, 30, 60, 120 min or 24 hr post-injection. Performance was affected in a dose-and time-dependent fashion. Peak carboxyhemoglobin (COHb) levels were observed at 15 or 30 min and were 20%, 32%, 42%, 51% and 60% for 7.5, 15, 30, 50 and 100 ml/kg CO, respectively. COHb saturation alone was not always a good predictor of behavioral effects since both level and duration of exposure contributed to behavioral impairment. The results also show that the IP route can be used to study the toxicity of CO.