cssi/SciSciGPT-SciSciNet huggingface dataset:
ATRIAL CHAMBER-SPECIFIC EXPRESSION OF THE SLOW MYOSIN HEAVY CHAIN 3 GENE IN THE EMBRYONIC HEART

The quail slow myosin heavy chain 3 (slow MyHC 3) gene is expressed in the developing heart and in slow muscles of the developing limb. It is first expressed in the pulsatile cardiac tube in the embryo, and as the heart chamberizes its expression becomes restricted to the atria. To identify regulatory elements responsible for atrial-specific expression, the 5′ upstream region of slow MyHC 3 gene was investigated. An atrial regulatory domain (ARD1) between −840 and −680 acts as an atrial cell-specific enhancer in primary cardiocyte cultures. ARD1 also specifies atrial-specific expression in vivo when the ARD1/heterologous promoter was introduced into developing chick embryos by a replication-competent retroviral vector. ARD1 is the first atrial cell-specific enhancer to be identified. Fine deletion and mutation analysis within ARD1 defined a 40-base pair vitamin D3 receptor-like element that controls atrial cell-specific expression of the slow MyHC 3 gene by inhibiting its expression in ventricular cardiocytes.
Two-year case collection of the Brugada syndrome electrocardiogram pattern at a large teaching hospital.

Background: Recommendations have recently emerged suggesting that the presence of the Brugada electrocardiographic (ECG) pattern in an otherwise asymptomatic individual warrants electrophysiologic testing for inducible ventricular arrhythmias. However, the prevalence of this pattern in the general population and its specificity for identifying those likely to develop the true Brugada syndrome are not known. Hypothesis: The purpose of this study was to collect ECGs that displayed the Brugada pattern from unselected, noncar-diac patients at a single institution to determine whether the implied prevalence in the literature may represent a significant underestimation of the true prevalence. Methods: We performed a prospective case collection of Brugada-patterned ECGs over a 2-year time period from unselected, noncardiac patients at a large urban teaching hospital. Results: Of approximately 12,000 noncardiac patients, 52 were found to have an ECG pattern fully consistent with the Brugada sign. Conclusions: The Brugada type ECG pattern is much more prevalent than previously reported when rigorously searched for in a prospective manner. More data are needed on its specificity for predicting future arrhythmic events in asymptomatic individuals before recommendations are made for extensive evaluation in this group.
8 Cross-sectional imaging of the pancreas

Abstract CT is the primary modality for the evaluation of patients with pancreatic disease. A number of pitfalls can occur in interpretation of the scans, but most can be avoided by using state-of-the art scanners and dynamic contrast enhancement techniques and by recognizing normal anatomic variants. However, in other cases, CT may show only nonspecific findings and a correct diagnosis can be reached only by utilization of additional imaging techniques or guided FNAB.
Urban growth and population densities.

Differences in the distribution of population within and across metropolitan areas are seen as a product of the development of the metropolis during different transportation epochs. Age cohorts of census tracts in Cleveland, Ohio, may be split into three groups of development patterns based on the time of their early development: (1) before the development of the automobile, (2) during the early period of the auto’s diffusion to the population, and (3) during the period of the mass diffusion of the auto. Patterns of population concentration and congestion across metropolitan areas are heavily selective of places with large population growth before the development of the streetcar and the automobile. More recent population growth has had little effect on population congestion but has led to a deconcentrated metropolis.
A new improved artificial bee colony algorithm for ship hull form optimization

The artificial bee colony (ABC) algorithm is a relatively new swarm intelligence-based optimization algorithm. Its simplicity of implementation, relatively few parameter settings and promising optimization capability make it widely used in different fields. However, it has problems of slow convergence due to its solution search equation. Here, a new solution search equation based on a combination of the elite solution pool and the block perturbation scheme is proposed to improve the performance of the algorithm. In addition, two different solution search equations are used by employed bees and onlooker bees to balance the exploration and exploitation of the algorithm. The developed algorithm is validated by a set of well-known numerical benchmark functions. It is then applied to optimize two ship hull forms with minimum resistance. The tested results show that the proposed new improved ABC algorithm can outperform the ABC algorithm in most of the tested problems.
The chemistry of xylylenes. X. Some polymers and telomers of spiro‐di‐o‐xylylene

Spiro-di-o-xylylene polymerizes via a free-radical mechanism to give high molecular weight poly(o-xylylene). It reacts with olefinic molecules, such as styrene, acrylonitrile, methyl methacrylate, vinylidine fluoride, and butadiene to give copolymers containing di-o-xylylene units in its backbone. Solutions of spiro-di-o-xylylene can be titrated with iodine, and di-o-xylylene-di-iodide is produced stoichiometrically. Telomers of di-o-xylylene are obtained when the spiro compound is allowed to react in the presence of chain transfer agents such as HSR and CBr4.
Estimation of Calcium Sulfate Solution Rate and Effective Aquifer Surface Area in a Ground-Water System Near Carlsbad, New Mexico

The geochemistry of a very permeable ground-water system containing calcium sulfate was studied to determine the present rate of dissolution. An estimate was made of the chemical composition of water recharging the system and the difference between that estimate and the composition of the ground water in the system was used to determine the minimum amount of calcium sulfate being dissolved under existing hydrologic conditions. This result was used, with published data on rates of calcium-sulfate dissolution, to determine the effective surface area involved in solution processes. Results indicate that flow in this system is through large solution openings, which are growing larger at a rate of a few tens of millimeters per year.
Structural characterization of partially folded intermediates of apomyoglobin H64F

We present a detailed investigation of unfolded and partially folded states of a mutant apomyoglobin (apoMb) where the distal histidine has been replaced by phenylalanine (H64F). Previous studies have shown that substitution of His64, located in the E helix of the native protein, stabilizes the equilibrium molten globule and native states and leads to an increase in folding rate and a change in the folding pathway. Analysis of changes in chemical shift and in backbone flexibility, detected via [1H]-15N heteronuclear nuclear Overhauser effect measurements, indicates that the phenylalanine substitution has only minor effects on the conformational ensemble in the acid- and urea-unfolded states, but has a substantial effect on the structure, dynamics, and stability of the equilibrium molten globule intermediate formed near pH 4. In H64F apomyoglobin, additional regions of the polypeptide chain are recruited into the compact core of the molten globule. Since the phenylalanine substitution has negligible effect on the unfolded ensemble, its influence on folding rate and stability comes entirely from interactions within the compact folded or partly folded states. Replacement of His64 with Phe leads to favorable hydrophobic packing between the helix E region and the molten globule core and leads to stabilization of helix E secondary structure and overall thermodynamic stabilization of the molten globule. The secondary structure of the equilibrium molten globule parallels that of the burst phase kinetic intermediate; both intermediates contain significant helical structure in regions of the polypeptide that comprise the A, B, E, G, and H helices of the fully folded protein.
Role of Three-Dimensional Matrix Stiffness in Regulating the Response of Human Neural Cells to Toxins

Recent studies have highlighted the strong influence of microenvironmental stiffness on various cell fates including proliferation, migration, and differentiation in both two- and three-dimensional culture conditions. Our study attempts to understand the role of 3D microenvironmental stiffness on cell cytotoxic response using neural glioblastoma U-87 cells encapsulated in alginate hydrogel matrices of varying stiffness as the model system. Interestingly, we observed that cells encapsulated in soft alginate matrices were more sensitive to the toxic chemicals relative to cells encapsulated in stiffer matrices. The observed dependence of toxic responses on matrix stiffness was also seen for other neural cell lines including U-251 glioblastoma and IMR-32 neuroblastoma cells. Given the established involvement of Rho GTPases in mediating mechanosensitive cell responses, we also performed the toxicity assays using U-87 cells expressing constitutively active mutants of the Rho GTPase RhoA. Under these conditions, the toxic responses were similar for U-87 cells cultured in both soft and stiff matrices. These results suggest a strong role of mechanotransductive signaling on the response of neural cells to toxins. We believe that determining the role of substrate stiffness on the toxic response of neural cells will be crucial to the development of optimal in vitro cell-based screens of neurotoxicity.
Using efficient bank insolvency resolution to solve the deposit insurance problem

Deposit insurance typically suffers from two well-known problems — for banks, moral hazard generated excessive risk taking, and for regulators, poor agency behaviour leading to excessive forbearance. The usual attempts to correct these problems by directly changing the structure of deposit insurance through coinsurance, risk-sensitive premiums, etc, have been largely unsuccessful. This paper proposes an indirect solution that focuses on efficient absolution of insolvent banks before their capital turns negative. If successful, no losses are suffered by insured or uninsured depositors. As a by-product, deposit insurance becomes effectively redundant, but not unnecessary to handle regulations that are not efficient. The paper expands on how to achieve efficient resolutions.
Evaluation of a new approach to life-long learning in civil and environmental engineering curricula

Lifelong learning (LLL) has been long recognized by educators as a valuable attribute that can be an impetus for improved student learning. The Accreditation Board for Engineering and Technology (ABET) criteria (2000) require that engineering programs produce "graduates who pursue life-long learning through continuing education and/or advanced degrees in engineering or related fields". Many colleges and universities have incorporated LLL into their program outcomes. However, it remains a challenge to identify effective methods to integrate and assess LLL into the engineering curriculum. Three years ago, two faculty (one Civil and one Environmental) at Florida Gulf Coast University redesigned two of their courses. They developed a new approach to respond to ABET LLL requirements. This year this new program has been implemented by additional faculty from other institutions. Data and surveys from nearly 400 students and associated faculty were collected The faculty survey identifies LLL approaches that faculty have implemented in their classrooms. Results obtained from the data analysis support the effectiveness of this approach; the students respond well to working with real life challenges, incorporating more critical thinking and research in their work.
Torsion-Free Modules with Nearly Unique Endomorphism Algebras

Let R be a discrete valuation domain and n ≥ 1. If the completion of R contains at least n algebraically independent elements over R, then there exists a torsion-free module M such that End R M is ...
Metabolic adaptation of Cancer irroratus developmental stages to cyclic temperatures

Metabolic-temperature responses of the developmental stages of the sublittoral crab Cancer irroratus cultured at 10° to 20°C daily cyclic and 15°C constant temperatures were determined. Generally, the metabolic rate increased with temperature in the lower range with Q10's (temperature coefficients) above 2, compensated in the midrange with Q10's between 1 and 2, and declined at the higher temperatures with Q10 values less than 1. For the larvae cultured at a constant temperature of 15°C, the compensatory response range narrowed with development from first zoeae to the later zoeal stages. In contrast, the compensatory response of the first zoeae, megalops, and crab stages within the range 10° to 25°C was interrupted by a zone of thermal sensitivity between 15° and 20°C for those individuals cultured in the 10° to 20°C cyclic regime. The compensatory response range is narrower for the third stage zoeae and broader for the second, fourth, and fifth stage zoeae. Metabolic rate-temperature (M-T) patterns of C. irroratus developmental stages cultured under the cyclic regime varied from those held at constant temperature by increased respiration and metabolic rate compensation between 20° and 25°C, and by an extension of the metabolically active range towards higher temperatures.
Non-intrusive technique for measurement of power spectra in compressible turbulence

We present exploratory tests of a new optical method which measures directly two components of the 3-D power spectrum of the refractive-index fluctuation. The method was applied to a Mach 2 turbulent shear layer. Length scales ofO.lmm to I.Omm were resolved within a shear-layer thickness ranging from 5n1m to 10mm. At lowto-moderate wavenumbers, the spectral behavior is roughly K ~ , while at higher wavenumbers it is K ~ . ~ . These spectra slopes are in agreement with prevailing theoretical predictions for anisotropic (lowwavenumber) and isotropic (high-wavenumber) turbulence. ..j
On a theorem of Mislin

Abstract A theorem of Mislin gives an equivalence between a condition on restriction of cohomology to a subgroup with an embedding condition on the subgroup. Two variations of this result are proved and a reduction is given towards a purely algebraic proof of Mislin's original theorem.
Survival cost of an intrasexually selected ornament in a damselfly

Ornaments could evolve as honest indicators of fighting ability, provided they have costs that make deceptive signalling unprofitable. I tested for such costs by manipulating the size of the intrasexually selected wing spots of male rubyspot damselflies (Hetaerina americana) and monitoring survival in the field. Males with enlarged spots had higher mortality rates than both unmanipulated and sham-manipulated controls. Natural wing spot size correlated positively with longevity, which suggests that higher quality males develop larger spots.
Response to Letter by Eggers

Response: We appreciate the comments by Dr Eggers regarding our recent editorial on a single-center pilot trial of sonothrombolysis with transcranial color-coded sonography (TCCS) and intravenous tissue plasminogen activator (tPA).1 Dr Eggers, who was the primary investigator of this trial,2 has raised 2 points that we would like to address. First, he underlines that our assumption concerning the potential association between the multibeam configuration of TCCS and the increased rate of symptomatic intracranial hemorrhage is not justified because the overwhelming part of the insonation was performed with pulsed-wave Doppler, whereas color-coded Duplex was used only for vessel identification. Because Eggers et al used no head frame …
Adaptive Multi-Class Signaling Control for Cellular Networks

In this paper, we propose a paradigm for signaling congestion control based on providing quality of service (QoS) to signaling traffic in wireless cellular networks (WCNs). An adaptive multi-class token bucket with an overflow buffer combined with priority scheduling is used to provide different grades of service to classes of signaling messages. Engineering specifically for WCNs, the signaling message congestion control is tied to the state of the traffic transport network. Simulation results are given illustrating the behavior of the new signaling overload control scheme and comparing it with existing schemes in the literature. The performance study shows that the proposed scheme can control congestion and improve performance.
Triple play: delivering effective & key communication

Students, faculty and staff receive and process information in different ways, leaving messengers with the challenge of uncovering various channels and tapping into those resources to make messages effective. The additional channels offered by technology make such a task even more challenging because more delivery options generally mean niche specialization and less penetration, leading to diluting and splintering of message content.The bottom line: people are becoming even more difficult to reach because of the seemingly endless number of messages bombarding them. And when those messages are difficult to understand (like many technology messages are), they generally are discarded in spite of potential importance or relevance.At the University of Missouri-Columbia, Information & Access Technology Services has developed an integrated approach to communicating with its various publics. The strategy is grounded in sending the same message to the same audience using different delivery models. Triangulation of messages to faculty, staff and students at MU has been successful in raising awareness, communicating news, advertising new services and getting action. The key is consistency and persistence in editorial and promotional approaches, tapping known, reliable channels and developing new ways to reach targeted publics.
Treatment of epigallocatechin-3-gallate inhibits matrix metalloproteinases-2 and -9 via inhibition of activation of mitogen-activated protein kinases, c-jun and NF-kappaB in human prostate carcinoma DU-145 cells.

BACKGROUND Matrix metalloproteinases (MMPs) are involved in tumor progression including the carcinoma of the prostate (CaP). Therefore, the effect of (−)-epigallocatechin-3-gallate (EGCG) was determined on the synthesis and activation of tumor invasion-specific MMP-2 and MMP-9 in human prostate carcinoma DU-145 cells. METHODS MMP-2 and MMP-9 were determined by zymography and Western blot analysis. Since fibroblast conditioned medium (FCM) partially mimics in vivo tumor-host microenvironment, DU145 cells were co-cultured in FCM. RESULTS Treatment of EGCG to DU-145 cells resulted in dose-dependent inhibition of FCM-induced pro and active both forms of MMP-2 and MMP-9 concomitant with marked inhibition of phosphorylation of ERK1/2 and p38. In identical conditions, treatment of EGCG or inhibitors of MEK or p38 to DU-145 cells inhibited FCM-induced phosphorylation of ERK1/2 and/or p38 concomitant reduction in MMP-2 and -9. EGCG also inhibited androgen-induced pro-MMP-2 expression in LNCaP cells. Further, treatment of EGCG also resulted in inhibition of activation of c-jun and NF-κB in in vitro DU-145 cells. CONCLUSIONS The inhibition of MMP-2 and MMP-9 in DU145 cells by EGCG is mediated via inhibition of phosphorylation of ERK1/2 and p38 pathways, and inhibition of activation of transcription factors c-jun and NF-κB. EGCG may play a role in prevention of invasive metastatic processes of both androgen-dependent and -independent prostate carcinoma. © 2003 Wiley-Liss, Inc.
Personal, social, and environmental correlates of physical activity in rural Midwestern white women.

Abstract Background Physical activity is a promising component of cardiovascular disease prevention among women. Research in this area is expanding, but much needs to be done to assess subgroups of the population (e.g., people living in rural environments). The study goal was to determine personal, social environmental, and physical environmental correlates of physical activity among rural white women aged 20 to 50 years. Methods A survey was conducted by using randomly selected numbers in rural areas in Missouri and Illinois. The Women and Physical Activity Survey was administered to assess physical activity status and personal, social environmental, and physical environmental factors. Physical activity status was the dependent variable in analyses comparing inactive women with women who performed any activity and comparing women who met current recommendations for moderate or vigorous physical activity with those women did not meet recommendations. Results Of the 1000 women in the study, 52% met recommendations for physical activity, 40.1% were insufficiently active, and 7.9% were inactive. Younger women (20–29 years) were more likely than the oldest age (40–50 years) category to perform some activity than to be inactive. Women in excellent or very good general health were much more likely to perform some physical activity than to be inactive. Higher income and employment were factors in meeting the recommendations. Attending religious services and a higher social roles score were significant factors. Having street lighting was the only physical environmental factor that emerged as statistically significant. Conclusions More research is needed on the assessment of important issues regarding physical activity in women. Interventions should use assessment information to tailor programs and to address personal, social environmental, and physical environmental components.
Georg Herwegh and the Aesthetics of German Unification

GEORG HERWEGH was preeminently the German political . poet of the i84o's. With youthful arrogance and unstable talent he burst onto the literary and political st ge in 1841 with the publication of his Gedichte eines Lebendigen. The contagious excitement generated by this work showed that he both touched and epitomized the revolutionary aspirations of Germany's intellectuals. Gottfried Keller described the immediate impact of Herwegh's work on him: "The new tone struck me like a trumpet blast which suddenly arouses a large camp ofthe people's army."1 And his reaction was typi? cal: Herwegh was feted by literary circles and political coteries impatient for the revolution that his poetry impelled. When the revolution did come in 1848, Herwegh led a battalion into battle, only to flee precipitately in defeat. But the poet outlived his reputation. He spent most of the years after 1848 in exile, growing increasingly estranged from Ger? many, his infrequent later poetry never equalling the vigor of his first verse. He had lived for revolution, and when that revolution failed he passed the rest of his life in futile and impotent grasping for the past or some imagined future. "They were like the court clock at Versailles, which pointed to one hour, the hour at which the King died," wrote Alexander Herzen, describing the empty lives ofthe exiled revolutionaries of 1848 like Herwegh. "And like the clock, they had not been wound up since the death of Louis XVI."2 Herwegh's political poetry thus lay under the indictment of its own politics. But even more, it lay under the pall of Heine's condemnation ofthe aesthetics of political poetry. A fear that poetry was degenerating into rhymed slogans motivated Heine's pronouncement against the
A note on ranked-set sampling using a covariate

Abstract Ranked-set sampling (RSS) and judgment post-stratification (JPS) use ranking information to obtain more efficient inference than is possible using simple random sampling. Both methods were developed with subjective, judgment-based rankings in mind, but the idea of ranking using a covariate has received a lot of attention. We provide evidence here that when rankings are done using a covariate, the standard RSS and JPS mean estimators no longer make efficient use of the available information. We first show that when rankings are done using a covariate, the standard nonparametric mean estimators in JPS and unbalanced RSS are inadmissible under squared error loss. We then show that when rankings are done using a covariate, nonparametric regression techniques yield mean estimators that tend to be significantly more efficient than the standard RSS and JPS mean estimators. We conclude that the standard estimators are best reserved for settings where only subjective, judgment-based rankings are available.
Critical evaluation of methods used for the isolation of rat liver hepatocytes for metabolic studies.

Abstract Hepatocytes were isolated from normal fed, fasted and alloxan diabetic animals. The best cell preparations were obtained by using low concentrations of collagenase (10–20 mg) and exposing the liver for a very short period of time (10–15 min). Addition of hyaluronidase significantly decreased the glycogen content of the isolated hepatocytes. Glucagon (10 −12 M) stimulated glycogenesis in hepatocytes containing high glycogen whereas, in cells containing low glycogen much higher concentration of glucagon was needed (10 −9 M). Addition of insulin (100 μunits) stimulated both glycogen and protein synthesis in isolated hepatocytes containing high glycogen. Under these conditions glycogen synthase activity was stimulated by 40%. Incorporation of 14 C phenylalanine into protein was linear for only 3–4 hr in cells containing low glycogen whereas, in cells containing high glycogen incorporating was linear for 8–10 hr. These studies suggest that intracellular glycogen plays an important role in the hormonal regulation of metabolism in hepatocytes.
Ecosystem response to 15 years of chronic nitrogen additions at the Harvard Forest LTER, Massachusetts, USA

Abstract Humans have altered the global and regional cycles of nitrogen more than any other element. Alteration of N cycling patterns and processes in forests is one potentially negative outcome of accelerated N deposition worldwide. To assess potential impacts of N deposition on temperate forests, a series of chronic nitrogen additions in two contrasting forest types (red pine plantation and mixed hardwood stand) were designed as a core experiment of the Harvard Forest (HF) Long-term Ecological Research (LTER) program. This paper describes the chronic N experimental study site in detail and presents the long-term baseline measurements established at the beginning of treatments in 1988. Results reported here continue or accelerate trends presented in previous papers. Losses of inorganic N remain high in the high N plots (higher in pines than hardwoods) and low N plots in the pine stand also have measurable DIN losses. Foliar and fine root N concentrations are elevated significantly. Mortality of red pine reached 56% by 2002 in the pine high N plot, and biomass accumulation has stopped altogether. The high N hardwood stand shows increased ANPP, but excess N availability and a severe drought in 1995 contributed to mortality of 72% of red maple trees by 2002. Species importance and litterfall patterns were altered in several plots after 1995. Roots, foliage and wood have diminished as net sinks for added N, re-emphasizing the role of soils in N retention. Two mechanisms for large net retention of added N were suggested in a review paper in 1998. Of these, abiotic immobilization is supported by a growing set of papers, while assimilation and re-exudation by mycorrhizae is suggested by increased DON concentrations.
Probiotic preparation VSL#3 alters the distribution and phenotypes of dendritic cells within the intestinal mucosa in C57BL/10J mice.

Probiotic nutrients have shown promise in therapy for the treatment of gastrointestinal inflammation, infection, and atopic disease. Intestinal dendritic cells (DC) play a critical role in shaping the intestinal immune response. In this study, we tested the effect of a probiotic preparation (VSL#3) on DC distribution and phenotypes within the intestinal mucosa using a lineage depletion-based flow cytometric analysis. In naive C57BL/10J mice, intestinal mucosal DC were composed of plasmacytoid DC (pDC) and myeloid DC (mDC). The pDC were the dominant form in lamina propria and Peyer's patches, whereas mDC were the prevailing type in the mesenteric lymph nodes. Additional characterization of pDC and mDC with flow cytometry revealed that they expressed heterogeneous phenotypes in the intestinal mucosa. In mice gavaged with the probiotic VSL#3 for 7 d, the proportion of pDC within the lamina propria was >60% lower, whereas the pDC subset in the mesenteric lymph nodes was more than 200% greater than in sham-treated controls (P < 0.01). Within pDC, the proportion of functionally unique CX3CR1(+) DC was greater than in controls in both the lamina propria and the Peyer's patches (P < 0.01). In contrast to pDC, the mDC number was greater than in controls in all intestinal lymphoid tissue compartments in VSL#3-treated mice (P < 0.01). In conclusion, this study suggests that phenotypically and functionally distinct DC subsets are localized to specific lymphoid tissues within the intestinal mucosa and that the VSL#3 probiotic nutritional supplement alters the distribution of the DC subsets within the intestinal mucosa. These changes may be important in the alteration of mucosal immunity following probiotic VSL#3 therapy.
Breakdown in Ceramic Capacitors Under Pulsed High-Voltage Stress

Failure in ceramic capacitors due to high-impulse voltages was investigated to determine the parameters which limit the breakdown voltage. It was found that the breakdown field strength is a function of the dielectric constant, the dielectric thickness, and the capacitor area. There was little correlation between the breakdown voltage and the rated voltage. Breakdown usually occurred at the edge of the electrodes, and only small changes in capacitance and dissipation factor resulted.
Free Somatostatin Receptor Fraction Predicts the Antiproliferative Effect of Octreotide in a Neuroendocrine Tumor Model: Implications for Dose Optimization

Somatostatin receptors (SSTRs) are highly expressed in well-differentiated neuroendocrine tumors (NET). Octreotide, an SSTR agonist, has been used to suppress the production of vasoactive hormones and relieve symptoms of hormone hypersecretion with functional NETs. In a clinical trial, an empiric dose of octreotide treatment prolonged time to tumor progression in patients with small bowel neuroendocrine (carcinoid) tumors, irrespective of symptom status. However, there has yet to be a dose optimization study across the patient population, and methods are lacking currently to optimize dosing of octreotide therapy on an individual basis. Multiple factors such as total tumor burden, receptor expression levels, and non-target organ metabolism/excretion may contribute to a variation in SSTR octreotide occupancy with a given dose among different patients. In this study, we report the development of an imaging method to measure surface SSTR expression and occupancy level using the PET radiotracer 68Ga-DOTATOC. In an animal model, SSTR occupancy by octreotide was assessed quantitatively with 68Ga-DOTATOC PET, with the finding that increased occupancy resulted in decreased tumor proliferation rate. The results suggested that quantitative SSTR imaging during octreotide therapy has the potential to determine the fractional receptor occupancy in NETs, thereby allowing octreotide dosing to be optimized readily in individual patients. Clinical trials validating this approach are warranted.
Structure, energetics, and mechanical stability of Fe-Cu bcc alloys from first-principles calculations

Atomic volumes, magnetic moments, mixing energies, and the elastic properties of bcc Fe1–xCux solid solutions are studied by ab initio calculations based on the cluster expansion framework. For the calculation of concentration-dependent elastic moduli in disordered solid solutions, we introduce a generalization of the cluster expansion technique that is designed to handle tensorial quantities in high-symmetry phases. Calculated mixing energies, atomic volumes, and magnetic moments are found to be in good agreement with available measurements for metastable alloys prepared through nonequilibrium processing techniques. Additionally, the predicted variations of the bulk modulus and shear moduli C44 and C[prime] with respect to copper concentration are calculated for the disordered bcc phase. While the bulk modulus and C44 are positive for all concentrations, C[prime] is predicted to be positive only for Cu concentration less than 50 atomic %, and negative otherwise. Our results thus indicate that the mechanical instability of bcc Cu persists over a wide range of compositions. The implications of the present results are discussed in relation to the observed metastability of bcc Fe-Cu alloys, and the strengthening mechanism of nanoscale bcc precipitates in an alpha-Fe matrix.
Aniline and its metabolites generate free radicals in yeast

The carcinogen aniline is negative in the Ames Salmonella mutagenicity assay. Aniline does, however, induce intrachromosomal recombination between repeated sequences in Saccharomyces cerevisiae, resulting in deletion (DEL) of intervening sequences. We have investigated whether the generation of oxidative free radical species by aniline and/ or its metabolites may be responsible for its recombinagenic activity in yeast. The toxicity and recombinagenicity of aniline in yeast were greatly reduced in the presence of the free radical scavenger N-acetyl cysteine. Aniline cytotoxicity was many-fold increased in strains of S.cerevisiae lacking the antioxidant enzyme superoxide dismutase. Aniline also induced oxidation of the intracellular free radical-sensitive reporter compound 2,4-dichlorofluorescin diacetate to its fluorescent derivative 2,4-dichlorofluorescein in vivo in S.cerevisiae. The aniline metabolites 4-aminophenol and 2-aminophenol were significantly more potent inducers of DEL recombination in yeast than aniline. In contrast, the secondary metabolite 4-acetamidophenol (acetaminophen) was non-toxic and non-recombinagenic in yeast. 4-Aminophenol and 2-aminophenol were also significantly more toxic than aniline in a superoxide dismutase deficient yeast strain. 4-aminophenol was a significantly more potent oxidizer of 2,4-dichlorofluorescin diacetate than aniline. The Escherichia coli soxS promoter, which is induced in the presence of redox cycling agents like paraquat, was induced weakly by aniline at toxic doses. The soxS promoter was strongly induced by 4-aminophenol and 2-aminophenol. The results indicate a role for oxidative stress, mediated by generation of superoxide radical, in the toxicity and recombinagenicity of aniline. The increased activity of 4-aminophenol and 2-aminophenol suggests that ring hydroxylation may be an important activating step in this process.
Early Duplication and Functional Diversification of the Opsin Gene Family in Insects

Recent analysis of the complete mosquito Anopheles gambiae genome has revealed a far higher number of opsin genes than for either the Drosophila melanogaster genome or any other known insect. In particular, the analysis revealed an extraordinary opsin gene content expansion, whereby half are long wavelength-sensitive (LW) opsin gene duplicates. We analyzed this genomic data in relationship to other known insect opsins to estimate the relative timing of the LW opsin gene duplications and to identify "missing" paralogs in extant species. The inferred branching patterns of the LW opsin gene family phylogeny indicate at least one early gene duplication within insects before the emergence of the orders Orthoptera, Mantodea, Hymenoptera, Lepidoptera, and Diptera. These data predict the existence of one more LW opsin gene than is currently known from most insects. We tested this prediction by using a degenerate PCR strategy to screen the hymenopteran genome for novel LW opsin genes. We isolated two LW opsin gene sequences from each of five bee species, Bombus impatiens, B. terrestris, Diadasia afflicta, D. rinconis, and Osmia rufa, including 1.1 to 1.2 kb from a known (LW Rh1) and 1 kb from a new opsin gene (LW Rh2). Phylogenetic analysis suggests that the novel hymenopteran gene is orthologous to A. gambiae GPRop7, a gene that is apparently missing from D. melanogaster. Relative rate tests show that LW Rh2 is evolving at a slower rate than LW Rh1 and, therefore, may be a useful marker for higher-level hymenopteran systematics. Site-specific rate tests indicate the presence of several amino acid sites between LW Rh1 and LW Rh2 that have undergone shifts in selective constraints after duplication. These sites and others are discussed in relationship to putative structural and functional differences between the two genes.
A high-throughput method for testing biofouling and cleaning of polymer hydrogel materials used in medical devices

A miniaturized, high-throughput method is developed to measure biofouling and cleaning processes of transparent silicone- and hydroxyethylmethacrylate-based polymer hydrogel materials used in medical devices. Protein biofouling and cleaning effectiveness were measured in 384-well microtiter plates using 3 mm biopsy punches from hydrogel materials soaked in a simulated protein soil fluid (PSF). Fluorescence detection of labeled protein components enabled highly sensitive quantification of biofouling and cleaning endpoints. The sample volume to soaking volume ratio and surface area to soaking volume ratio are similar to those used for full-sized analysis. The method showed minimal perturbation from sample height variations up to hundreds of micrometers. A calibration curve constructed by testing samples soaked in eight different concentrations (0–1.25 mg mL−1) of fluorescent protein showed a broad dynamic range, but fluorescence quenching occurred above 0.75 mg mL−1 protein in highly absorbing hydrogels. The method was found to have 1 : 1 linear correlation with measurements obtained by 2D fluorescence imaging using biofouled/cleaned miniature punches, and 3D confocal fluorescence profiling using full-sized samples soaked in PSF. A comparison of protein biofouling on two types of hydrogel materials revealed that the slope of protein concentration–response curves for high water materials was 100-fold higher than for low water materials. To demonstrate simultaneous measurement of biofouling by multiple soil components, lipid and protein sorption were also tested and found to be correlated. The characterization and results obtained here show the potential of this method for exploring mechanistic details of biofouling and cleaning processes. The method greatly decreases the time and cost associated with the large number of unique samples required, making it possible to study the roles of the numerous material, solution and soil variables at the biointerface of medical devices.
Co-W as an advanced barrier for intermetallics and electromigration in fine-pitch flipchip interconnections

The trend towards thinner packages with embedded active components in case of RF modules, and higher I/O densities in case of multicore processors or 3D ICs, are pushing interconnection technologies to its fundamental limits. The limitations of traditional solder bump technologies in terms of its fatigue resistance, current-handling, electromigration and thermomigration resistance has shifted the interconnection focus to advanced thick copper bump UBMs with solder caps. However, even these interconnections fail to meet thermo-mechanical and electrical reliability requirements for fine-pitch flipchip interconnections at high current densities where electromigration becomes a major concern. This paper explores Co-W as an advanced barrier between copper bump and solder cap for fine-pitch flipchip technology to improve electromigration resistance. By suppressing the intermetallic growth and controlling electromigration, the novel barrier is expected to enhance the current-handling and thermomechanical reliability. In a systematic experimental study, Cu-Sn diffusion and intermetallic growth rate of this new Cu-Co-W-Sn-Ag approach are compared with that of Cu-Sn-Ag with XPS depth-profiling and cross-section analysis using SEM and EDS. Based on the analysis, the benefits of Co-W as a solder barrier for fine-pitch flipchip interconnections at high current densities is presented
Silsesquioxane-based 193 nm bilayer resists: characterization and lithographic evaluation

Polysilsesquioxane-based 193 nm positive bilayer resists are described. In this design Si for etch resistance is placed in every repeat unit and acid-labile protected and acidic groups (and polar units) are in the side chain, allowing to incorporate each lithographically critical functionality in sufficient quantity. Fluoroalcohol is employed as an acid group instead of carboxylic acid because of its more attractive dissolution properties. Polymers were carefully analyzed by 19F, 13C, and 29Si NMR to determine composition and to quantify residual acetyl, silanol, and Q/T. Hydrogen-bonding between tertiary ester and fluoroalcohol in the polysilsesquioxanes was investigated by FT-IR and the effect of lactone incorporation on the thermal deprotection temperature elucidated. In order to better understand the dissolution behavior of exposed resist films, the silsesquioxane resist polymers were partially (ca. 30%) and fully deprotected in solution with acid and their dissolution kinetics investigated by using a quartz crystal microbalance (QCM). It has been found that the exposed areas of the silsesquioxane resists can have a very fast dissolution rate (Rmax) of >20,000 A/sec (or even >100,000 A/sec). Heating the fully deprotected model polymers to 150°C did not reduce the dissolution rate much, suggesting thermal condensation of silanol end groups is insignificant. Model deprotected polymers containing triphenylsulfonium nonaflate were exposed to 254 nm radiation, baked, and subjected to QCM measurements in order to determine whether or not acid-catalyzed silanol condensation would reduce the dissolution rate. A combination of high dose and high temperature bake resulted in significant reduction of the dissolution rate in the silsesquioxane polymer containing a small trifluoroalcohol. However, the dissolution behavior of the polymer bearing a bulky norbornene hexafluoroalcohol was unaffected by exposure and bake. Chemical and development contrast curves were generated by using a temperature gradient plate and bake temperature effects investigated. While a postapply bake temperature variation from 95 to 130°C did not affect the contrast (chemical and development) and sensitivity, a postexposure bake temperature effect was quite small. The process window of the silsesquioxane bilayer resists was comparable to that of a high performance commercial 193 nm single layer resist for both isolated and nested contact hole imaging, Superior performance of our silsesquioxane resist was demonstrated in patterned etch in comparison with a COMA-based bilayer resist.
Local delivery of r-hirudin by a double-balloon perfusion catheter prevents mural thrombosis and minimizes platelet deposition after angioplasty.

BACKGROUND The major morbidity of percutaneous transluminal coronary angioplasty is acute thrombosis and restenosis of the dilated lesion. Platelet-thrombus deposition occurs within minutes after injury, is primarily mediated by thrombin, causes acute occlusion, and contributes to late restenosis. Experimentally, specific thrombin inhibitors have prevented mural thrombosis. However, local therapy may be more effective than systemic treatment. We tested the hypothesis that high local concentrations of an antithrombin drug at the site of arterial injury following balloon angioplasty inhibit platelet thrombus formation equally or better than conventional systemic treatment and at lower systemic anticoagulant levels. METHODS AND RESULTS Balloon angioplasty of the carotid arteries of 29 pigs was performed using systemic intravenous treatment with heparin (100 U/kg, groups I and II), suboptimal r-hirudin (0.3 mg/kg, group III), and higher-dose r-hirudin (0.7 mg/kg, group IV), which is the lowest dose that completely inhibited arterial thrombosis in the pig. Immediately after balloon angioplasty of the first carotid, additional local therapy with placebo (group I) or r-hirudin (groups II, III, and IV; 0.3 mg/kg in 1 mL) was administered with distal perfusion through a new percutaneous double-balloon catheter. After 1 hour of local drug delivery, angioplasty of the contralateral carotid was performed. Reflow for 1 hour was permitted to both carotids to compare the short-term effect of local plus systemic treatment with systemic treatment on quantitative 111In-labeled platelet deposition and macroscopic mural thrombus formation on deeply injured carotid segments. Local drug delivery of placebo compared with systemic heparin treatment resulted in no change of platelet deposition (x 10(6)/cm2, mean +/- SEM) in controls (group I, 91.0 +/- 23.5 versus 80.8 +/- 19.4), but local delivery of r-hirudin resulted in a significant reduction in group II (15 +/- 2.5 versus 71.3 +/- 14.5; P < .02) and group III (11.4 +/- 2.5 versus 80.5 +/- 11.4; P < .01) and was borderline in group IV (7.4 +/- 1.8 versus 14.1 +/- 7.4; P = .05), respectively. The incidence of macroscopic mural thrombus formation with local and systemic treatment was 86% and 75% in group I, 16% and 70% in group II, 14% and 71% in group III, and 0% and 16% in group IV, respectively. CONCLUSIONS Local therapy with the specific thrombin inhibitor r-hirudin significantly reduces short-term quantitative platelet deposition and macroscopic mural thrombus formation following balloon angioplasty compared with systemic treatment of conventional doses of heparin and hirudin and requires a significantly smaller amount of the recombinant drug.
Species richness and temperature influence mussel biomass: a partitioning approach applied to natural communities

To increase the generality of biodiversity-ecosystem function theory, studies must be expanded to include real communities in a variety of systems. We modified J. W. Fox's approach to partition the influence of species richness on standing crop biomass (net biodiversity effect) of 21 freshwater mussel communities into trait-independent complementarity, trait-dependent complementarity (species with particular traits dominate without impacting other species), and dominance effects (species with particular traits dominate at the expense of others). Overall, species-rich mussel communities have greater biomass than predicted based on average biomass across the region. This effect is largely due to trait-independent complementarity with less abundant species having higher body condition and reduced metabolic rates in species-rich communities. These measures are positively correlated with spatial and temporal thermal variation, suggesting that use of thermal niches as habitat may be important to species coexistence and performance, and emphasizing that knowledge of species traits and environmental context are important to understanding biodiversity-ecosystem function dynamics.
Selecting neural network architectures via the prediction risk: application to corporate bond rating prediction

The notion of generalization can be defined precisely as the prediction risk, the expected performance of an estimator on new observations. The authors propose the prediction risk as a measure of the generalization ability of multi-layer perceptron networks and use it to select the optimal network architecture. The prediction risk must be estimated from the available data. The authors approximate the prediction risk by v-fold cross-validation and asymptotic estimates of generalized cross-validation or H. Akaike's (1970) final prediction error. They apply the technique to the problem of predicting corporate bond ratings. This problem is very attractive as a case study, since it is characterized by the limited availability of the data and by the lack of complete a priori information that could be used to impose a structure to the network architecture. >