cssi/SciSciGPT-SciSciNet huggingface dataset:
KRAS amplification in metastatic colon cancer is associated with a history of inflammatory bowel disease and may confer resistance to anti-EGFR therapy

Mutations in RAS occur in 30–50% of metastatic colorectal carcinomas (mCRCs) and correlate with resistance to anti-EGFR therapy. Consequently, mCRC biomarker guidelines state RAS mutational testing should be performed when considering EGFR inhibitor treatment. However, a small subset of mCRCs are reported to harbor RAS amplification. In order to elucidate the clinicopathologic features and anti-EGFR treatment response associated with RAS amplification, we retrospectively reviewed a large cohort of mCRC patients that underwent targeted next-generation sequencing and copy number analysis for KRAS, NRAS, HRAS, BRAF, and PIK3CA. Molecular testing was performed on 1286 consecutive mCRC from 1271 patients as part of routine clinical care, and results were correlated with clinicopathologic findings, mismatch repair (MMR) status and follow-up. RAS amplification was detected in 22 (2%) mCRCs and included: KRAS, NRAS, and HRAS for 15, 5, and 2 cases, respectively (6–21 gene copies). Patients with a KRAS-amplified mCRC were more likely to report a history of inflammatory bowel disease (p < 0.001). In contrast, mutations in KRAS were associated with older patient age, right-sided colonic origin, low-grade differentiation, mucinous histology, and MMR proficiency (p ≤ 0.017). Four patients with a KRAS-amplified mCRC and no concomitant RAS/BRAF/PIK3CA mutations received EGFR inhibitor-based therapy, and none demonstrated a clinicoradiographic response. The therapeutic impact of RAS amplification was further evaluated using a separate, multi-institutional cohort of 23 patients. Eight of 23 patients with KRAS-amplified mCRC received anti-EGFR therapy and all 8 patients exhibited disease progression on treatment. Although the number of KRAS-amplified mCRCs is limited, our data suggest the clinicopathologic features associated with mCRC harboring a KRAS amplification are distinct from those associated with a KRAS mutation. However, both alterations seem to confer EGFR inhibitor resistance and, therefore, RAS testing to include copy number analyses may be of consideration in the treatment of mCRC.
New insights into hydraulic fracturing fluids used for high-temperature wells

Abstract Current interest in deep, low-permeability formations ( The experimental fracturing-fluid solutions were prepared at a total polymer concentration of 30 and 40 lb/1000 gal. Additives such as synthetic polymer, oxygen scavengers, crosslinkers, crosslinker delay additives, and pH buffers were examined in this work. Hydrated polymer solutions were crosslinked with a metallic crosslinker between 200 and 400 °F. Viscosity measurements were carried out in a high-pressure/high-temperature (HP/HT) rheometer to evaluate rheology and thermal stability. Results show that adding a synthetic polymer and a crosslinker with the slowest reaction rate improves the fracturing fluid thermal stability. Of the three other additives tested, oxygen scavengers showed the greatest enhancement to thermal stability while pH buffers showed the least. Through the addition of high-temperature stabilizing additives, the fracturing fluid in this work was able to maintain a stable performance at temperatures up to 400 °F. Maintaining the thermal stability of fracturing fluids at a lower polymer loading remains a challenge in the industry. This work proposes techniques that can be used to enhance the thermal stability of fracturing fluids. Deeper knowledge about these different techniques will allow for better additive development and application in the field.
Three-Dimensional Analysis of Laminar Composites with Through Cracks

The variational principle of minimum complementary potential energy is employed to develop an approximate three-dimensional model for the stress distribution in laminar composites. This approximate theory is applied to the problem of a symmetric composite plate containing a through crack subjected to in-plane loading. Asymptotic solutions are obtained for the stress components in the vicinity of the leading crack edge. These solutions are in complete agreement with information obtained from an exact three-dimensional asymptotic analysis; that is, the in-plane variation of the stress components within each layer is described by the singular portion of the elastic, plane-strain crack solution. However, because of the three-dimensional character of the problem, the amplitude of the singular solution for the stress components varies along the leading crack edge. A two-parameter model incorporating the concept of surface and interfacial boundary layers is used to describe this transverse variation. Results from the modeling and analysis performed here include a description of the through-the-thickness-variation of the near-tip stress field, which has already proven to be of use in conjunction with photoelastic measurements, and an average or effective stress intensity factor for finite thickness homogeneous plates and laminates.
Reducing susceptibility to moisture damage in asphalt pavements using polyethylene terephthalate and sodium montmorillonite clay

Abstract This study examines the feasibility of developing built-in resistance against moisture damage using either passivation or an arresting mechanism. A specific moisture-susceptible paving mixture with proven moisture-damage issues in the field was selected for this study. The damage was attributed to failure at the interface of bitumen and stone aggregate due to accumulation of acidic compounds at the interface with subsequent dissolution in the presence of water. Here, we examine two remedial methods. The first method introduces a polyethylene terephthalate based additive (PET) to bitumen to neutralize active sites of stones with concentrations of silica oxide greater than 50% (denoted simply as siliceous stones), suppressing nucleation and growth of acids at the interface. The second method introduces sodium montmorillonite clay (MMT) to adsorb acids and prevent their migration to the interface of stone and bitumen. Measurement of shear binding between siliceous substrates and bitumen using a shear rate sweep test showed increases of 21% and 43% due to the inclusion of MMT and PET, respectively. This improvement was also observed in the results of bitumen bond-strength tests performed on glass and on stone substrates. Results of the evaluation at the mixture level using a Hamburg wheel-tracking test showed that the addition of MMT and PET improved resistance to moisture damage, as evidenced by the increasing number of cycles before moisture stripping occurs. For the PET-modified mixture, no stripping inflection was observed until 20,000 cycles. It was also observed that MMT’s adsorption of acidic compounds from bitumen led to the appearance of surface dents after water conditioning. The PET-modified specimen showed some signs of color change after water exposure, without any signs of stripping. The study results help formulators design materials with built-in resistance mechanisms against moisture damage.
Analysis and Design of Membrane Processes

Analysis and Design of Membrane Process: A Systems Approach highlights the fundamentals and emerging technology in the field of industrial reverse osmosis desalination and membrane processes. It provides a unique, systems engineering perspective of membrane operation, focusing on analysis, design, and optimization of membrane processes. An explanation of mathematical and optimization knowledge is introduced and then applied throughout the book.Key topics include: •Hydrodynamics and mass transfer in reverse osmosis (RO) membranes•Predictive models for RO module performance•Analysis and optimization of brackish and seawater RO desalination•Energy production using pressure retarded osmosis (PRO)•Integration of RO and PRO for energy-efficient desalination•Dynamic operation of batch RO and batch PROThis work is essential reading for researchers who are interested in membrane-based processes, and those working within the water industry as well as undergraduate and graduate students.
From the archives of MD Anderson Cancer Center: A case of concurrent follicular lymphoma and Langerhans cell sarcoma with a review of the literature

Transdifferentiation of follicular lymphoma to a Langerhans cell neoplasm is rarely reported and not well understood. Here we present a case, review the literature and discuss some of the biological underpinnings of lineage switch of B cells to histiocytes/Langerhans cells. A 31-year-old woman had follicular lymphoma (FL) and Langerhans cell sarcoma (LCS) co-localized above and below diaphragm. The FL was low-grade, had typical morphologic features, and was positive for CD10, BCL-2, and BCL-6. The LCS was cytologically atypical with necrosis and a high mitotic rate, and the immunophenotype supported Langerhans cell lineage positive for CD1a, CD207/langerin, and S-100 protein. Both tumors carried IGH-BCL2 and the LCS cells had immunophenotypic evidence of a residual B cell program, supporting the notion that these neoplasms are clonally related. The case reported is unusual because the patient was young and both diseases presented simultaneously, before any therapy. In addition, immunohistochemical analysis showed that the LCS was negative for BRAF V600E and phospho-ERK, suggesting that the LCS belongs to the known subset of Langerhans cell tumors lacking BRAF V600E and MAP2K1 mutations. Concurrent occurrence of FL and Langerhans cell neoplasm is an unusual phenomenon, with 10 cases reported previously: 4 Langerhans cell histiocytosis and 6 Langerhans cell sarcoma, including this case.
Asymmetric equilibrium core structures of pyramidal-II 〈 c + a 〉 dislocations in ten hexagonal-close-packed metals

The structures of pyramidal-II $\ensuremath{\langle}c+a\ensuremath{\rangle}$ dislocations, one of the most important defects in structural hexagonal-close-packed (HCP) metals, have not been fully characterized for many of the HCP metals in use today. Here, we employ ab initio informed phase-field dislocation dynamics to determine the minimum energy structure of pyramidal $\left\{\overline{1}\overline{1}22\right\}\ensuremath{\langle}11\overline{2}3\ensuremath{\rangle}$ dislocations in ten HCP metals, including Be, Co, Mg, Re, Ti, Zn, Cd, Hf, Y, and Zr. As input for the simulations, we calculate, using first-principles density functional theory, the $\left\{\overline{1}\overline{1}22\right\}$ generalized stacking fault energy (GSFE) curves for all ten metals. From these calculations, it is found that magnetism in Co is necessary for achieving a local minimum in the GSFE curve. We observe in simulations that edge and screw character dislocations split into two partials separated by a low-energy intrinsic stacking fault. The splitting distance is shown to scale inversely with the local minimum energy normalized by the product of its shear modulus and Burgers vector. Interestingly, some HCP metals exhibit an asymmetric structure, with either unequal partial Burgers vectors or widths, in contrast to the symmetric configuration expected from linear elastic dislocation theory. We explain these structures by properties of the local maxima in their GSFE curves. Metals with larger degrees of elastic anisotropy result in dislocations with larger splitting distances than would be expected under the commonly used assumption of elastic isotropy. These findings on the sizes and asymmetry in the structures of pyramidal-II $\ensuremath{\langle}c+a\ensuremath{\rangle}$ dislocations are fundamental to understanding how these dislocations glide and interact or react with other defects when these metals are mechanically strained.
Cross-linked polyrotaxane to improve mechanical properties of oil well cement

We have developed cross-linked polyrotaxane (cPR) that is composed of moveable cross-links and slide-ring components, in its backbone. The cPR is blended with oil well cement to improve elastic properties, and it has demonstrated improvement in elastic modulus with minimum effect on compressive strength. The optimization of curing time, fluid flow behavior, and dynamic strength development in the presence of cPR in cement are also evaluated. The Young’s modulus and compressive strength are measured at 20 MPa and 150°C to simulate downhole conditions. Remarkably, cement—cPR has, revealed a 33% increase in strain compared to neat cement.
Effect of Baseline Mental Health on 1-Year Outcomes After Hip Arthroscopy: A Prospective Cohort Study.

Background:Patient factors, including mental health, sex, and smoking, have been found to be more predictive of preoperative hip pain and function than intra-articular findings during hip arthrosco...
The Bottom Line Is Progress: All the Rest Is Commentary

Response to Julio C. de Rose’s comments: “Will the Wing Fly Away from the Body? A Commentary on Steven Hayes’ Chapter, Contextual Behavioral Science.”
Tumor Microenvironment: Immune Effector and Suppressor Imbalance

Despite the broad clinical use of immune checkpoint inhibitors (ICI), prominent questions remain relative to their mechanism of action and optimal patient selection strategies. Enhanced understanding of tumor/immune cell interactions in the tumor microenvironment (TME) and identification of dominant immune evasion pathways in the context of individual patients will be required to expand the impact of immunostimulatory anti-cancer therapies. This chapter summarizes current evidence about immune stimulatory and suppressor signals in the TME focusing on their dynamic interplay in human non-small cell lung cancer, expected tumor tissue/cell location and potential for therapeutic targeting. We also discuss the role of molecular TME immune features as biomarkers and their potential impact in future cancer therapeutics.
Putting the horse back before the cart: designing strategic social enterprises

In this commentary on a case study of Unjani Clinics, I argue that the weak state of current social entrepreneurship practice—marked by the widespread prevalence of internal organizational conflict and mission-drift—reflects the lack of application of basic strategic and organization design principles to this important area. As the Unjani case study demonstrates, when strategically conceived and creatively designed, social enterprises can not only achieve both their commercial and social missions, but do so in a way that is supermodular compared to the governance forms of which they are a hybrid. If many, if not most, social enterprises fail to meet that standard, it is not because the tools to manage conflicting objectives within hybrid organizations do not exist, but because the lack of market discipline leaves substantial room for inefficiency in such organizations, resulting in the proliferation of ill-conceived and poorly implemented social ventures.
The Prevention and Treatment of Coronary Artery Disease in Kidney Transplant Recipients

Cardiovascular disease (CVD) is the leading cause of death amongst renal transplant recipients. Pre-transplant evaluation of cardiovascular risk in potential recipients is the standard for most transplant centers, though the method of evaluation varies. Risk factors for CVD are prevalent amongst patients with chronic kidney disease and include diabetes, hyperlipidemia, hypertension, and smoking.
Long run patterns of corporate R&D expenditure: A descriptive analysis of the period 1965 to 1984

Abstract This paper examines two decades of R&D performance (1965–1984) for seven research-intensive industries in the U.S. The analysis uses two measures of R&D effort, R&D as a percent of sales and R&D per employee, and considers both the intensity and the stability of R&D spending. R&D data are taken from the Compustat tapes. R&D expenditures are deflated using new R&D deflators provided by Mansfield [6]. The analysis shows that most industries exhibited a U-shaped pattern of R&D intensity (six of seven when measured by R&D as a percent of sales), with R&D expenditures declining from the mid-1960s to the mid-1970s and then rebounding from the mid-1970s to the early 1980s. As to stability of R&D spending, the analysis shows that continuous process industries (chemicals, drugs and pharmaceuticals, soaps and detergents) have greater stability in R&D effort, while fabrication and assembly industries (computer peripherals, electronic equipment, missiles and aircraft) show greater variability. The study sets forth a series of research questions about the relationship between these patterns and an industry's structure, performance and competitive position.
Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage

Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER) causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR) leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.
Isolation and characterization of the peptides derived from soluble human and baboon skin collagen after cyanogen bromide cleavage.

Abstract The α1 and α2 chains of soluble collagen from human and baboon skin were separated and cleaved with cyanogen bromide, and the resultant peptides were separated by ion exchange and molecular sieve chromatography. Eight peptides from the α1 chain and six from the α2 chain accounted for the weight and amino acid content of both collagens. Only small differences of questionable significance could be detected between the collagens of the two primate species by amino acid analysis or molecular weight of the peptides. The amino-terminal cross-link region of both the α1 and α2 chain is identical in both species. The peptides are very similar to those previously isolated from the rat and the chick, demonstrating a close homology in the helical portion of the molecule and, to a lesser extent, in the amino-terminal crosslink region.
A component analytic approach to precipitation regionalization in California

Four precipitation regions in California are identified and described using P-mode principal components analysis. A regionalization of regimes was accomplished by classifying data points (precipitation stations) with respect to which component they loaded highest on. Three primary regions were found to exist and their spatial extent is presented in map form. Data for study were 120 monthly precipitation totals observed from 1961–1970 at each of 90 randomly selected stations within California.
The Application of Faint Minor Planet Dynamics to the Problems of Improving the Fundamental Reference System

The underlying method of forming the adopted Fundamental Reference System is the compilation of observations referred to some (independent) well defined coordinate systems. If the observations themselves are used to define the independent coordinate system, they may be used to help establish the Fundamental System. If the observations are differential, they may be used to refer star positions to the Fundamental System and/or smooth systematic irregularities within the Fundamental System.
Protein metabolism during weight reduction with very-low-energy diets: evaluation of the independent effects of protein and carbohydrate on protein sparing.

The aim of this study was to assess the independent effects of carbohydrate and protein intakes in protein sparing during weight reduction. Forty-eight obese women were randomly assigned to consume isoenergetic (2500 kJ/d) liquid diets that provided the following amounts (g/d) of protein and carbohydrate, respectively, for 28 d : 50 and 10, 50 and 76, 70 and 10, and 70 and 86. The effects of carbohydrate and protein were analyzed by repeated-measures analysis of variance (ANOVA). Carbohydrate significantly affected daily urinary ammonia and total nitrogen excretion, stool nitrogen, and nitrogen balance. Protein, independently of carbohydrate, significantly affected daily urinary ammonia, urea, and total nitrogen excretion but had no effect on nitrogen balance. Cumulative nitrogen losses (mmol/28 d) were lower in the high-carbohydrate groups than in the low-carbohydrate groups (1869 ± 392 and 3611 ± 328, P = 0.003) but were similar in the groups receiving 50 and 70 g protein/d (3171 ± 327 and 2326 ± 430, respectively, P = NS). These results indicate that carbohydrate and protein have independent but additive protein-sparing effects during weight reduction. Am J Clin Nutr 1995 ;62 :93-103.
The Structure of Technological Revolutions and the Gutenberg Myth

We seem always today to be in the midst of one technological revolution or another. We imagine the future shaped by them. And in our accounts of the past, we point to them as significant forces that have given form and direction to our civilizations. Yet nowhere do we find any substantive discussion as to what exactly a technological revolution is. In fact, we refer to them as though their nature were obvious. We make use of historical examples to characterize the appearance of exciting new technologies and to prescribe ways for dealing with their “impact.” And we make these comparisons and prescriptions with such alacrity as to suggest that an explication of what we take the form of a technological revolution to be is simply unnecessary. In these various ways we have, nonetheless, developed an implicit characterization of technological revolutions that consistently results in alarmingly faulty histories and a posture toward current technologies that is frighteningly misleading and ultimately irresponsible. My aim here is to begin to surface this characterization, which I call the Gutenberg Myth, and to suggest that we are in need of an historically and conceptually more accurate and prescriptively more responsible understanding of the structure of technological revolutions.
Computing by Means of Physics-Based Optical Neural Networks

We report recent research on computing with biology-based neural network models by means of physics-based opto-electronic hardware. New technology provides opportunities for very-high-speed computation and uncovers problems obstructing the wide-spread use of this new capability. The Computation Modeling community may be able to offer solutions to these cross-boundary research problems.
Persistence of ethanol self-administration as a function of interreinforcer interval and concentration

Dipper cups filled with an ethanol solution were presented to Long-Evans hooded rats according to multiple extinction x s fixed-ratio 1 (mult EXT x s FR1) schedules of reinforcement. The scheduled duration of the EXT component was varied to manipulate minimum interreinforcer interval. Increasing the minimum interreinforcer interval by increasing the EXT component was used to challenge responding maintained by ethanol for purposes of evaluating the persistence of ethanol-maintained responding. EXT durations of 0 s (baseline conditions of continuous reinforcement) to 480 s were examined across ethanol concentrations of 0 (water, vehicle), 2, 4, 8, 16, and 32% (w/v). Increasing the EXT component duration resulted in reductions in the number of dipper presentations obtained at each concentration. Reductions in dipper presentations were less, relative to 0-s baseline conditions, the higher the concentration of the ethanol solution available. It was concluded that increasing the ethanol concentration that is self-administered increases the strength of responding that is subsequently maintained in that drug-maintained behavior becomes more resistant to modulation by a procedure (scheduling minimum interreinforcer intervals) which generally reduces numbers of drug deliveries.
"Mindless" decision making as a failure of contextual reasoning.

People often make decisions without reference to vital information, even when such information is readily available. In the present research, the authors addressed the possibility that this tendency may derive from failure to have pertinent information immediately available in the decision context. Participants rated the utility of decisions in either the presence or absence of simple pertinent information. The information provided required no training and was relatively obvious (e.g., if money is spent on a given item, that money will not be available for other expenditures). Presentation of such information in the immediate context of decisions significantly improved participants' abilities to understand their negative consequences. These results indicate that the presentation of pertinent information in immediate decision contexts, even information that is already available through participants' long-term memory, can improve the understanding of decision situations and reduce "mindlessness" in decision processes.
Nanoporous Gold Electrode for Electrochemical Sensors in Biological Environment

Abstract This work describes the use of nanoporous gold as an electrode material for biosensing applications. Nanoporous gold electrodes are fabricated, and their electrochemical performance is compared to plain gold electrodes of similar dimensions. For the detection of potassium ferricyanide, the nanoporous gold electrodes show improved sensitivity and higher currents compared to planar gold electrodes. Furthermore, the nanoporous electrodes show slower adsorption kinetics and maintain a significantly higher active electrochemical surface area in the presence of fragmented amyloid beta proteins.
Maintenance of Paternal Methylation and Repression of the Imprinted H19 Gene Requires MBD3

Paternal repression of the imprinted H19 gene is mediated by a differentially methylated domain (DMD) that is essential to imprinting of both H19 and the linked and oppositely imprinted Igf2 gene. The mechanisms by which paternal-specific methylation of the DMD survive the period of genome-wide demethylation in the early embryo and are subsequently used to govern imprinted expression are not known. Methyl-CpG binding (MBD) proteins are likely candidates to explain how these DMDs are recognized to silence the locus, because they preferentially bind methylated DNA and recruit repression complexes with histone deacetylase activity. MBD RNA and protein are found in preimplantation embryos, and chromatin immunoprecipitation shows that MBD3 is bound to the H19 DMD. To test a role for MBDs in imprinting, two independent RNAi-based strategies were used to deplete MBD3 in early mouse embryos, with the same results. In RNAi-treated blastocysts, paternal H19 expression was activated, supporting the hypothesis that MBD3, which is also a member of the Mi-2/NuRD complex, is required to repress the paternal H19 allele. RNAi-treated blastocysts also have reduced levels of the Mi-2/NuRD complex protein MTA-2, which suggests a role for the Mi-2/NuRD repressive complex in paternal-specific silencing at the H19 locus. Furthermore, DNA methylation was reduced at the H19 DMD when MBD3 protein was depleted. In contrast, expression and DNA methylation were not disrupted in preimplantation embryos for other imprinted genes. These results demonstrate new roles for MBD3 in maintaining imprinting control region DNA methylation and silencing the paternal H19 allele. Finally, MBD3-depleted preimplantation embryos have reduced cell numbers, suggesting a role for MBD3 in cell division.
Water vapor variations in the Venus mesosphere from microwave spectra

Abstract Mm-wave spectra of HDO in the Venus mesosphere (65–100 km) were obtained over the period March 1998 to June 2004. Each spectrum is a measurement of the hemispheric-average H2O vapor mixing ratio in the Venus mesosphere. Observations were conducted for wide ranges of Venus solar elongations (46° W to 47° E), and fractional disk illuminations ( f = 0 % to 99%), yielding water vapor abundances on 17 dates and over a full range of local solar time (LST) at the sub-Earth point on Venus. Our mesopheric H2O values are more numerous and far more precise than the earliest mm-derived H2O measurements [Encrenaz, Th., Lellouch, E., Paubert, G., Gulkis, S., 1991. First detection of HDO in the atmosphere of Venus at radio wavelengths: An estimate of the H2O vertical distribution. Astron. Astrophys. 246, L63–L66; Encrenaz, Th., Lellouch, E., Cernicharo, J., Paubert, G., Gulkis, S., Spilker, T., 1995. The thermal profile and water abundance in the Venus mesosphere from H2O and HDO millimeter observations. Icarus 117, 162–172], allowing an analysis of variability that was previously impossible. Measured 65–100 km H2O ranged from 0.0 ± 0.06 to 3.5 ± 0.3 ppmv , with significantly different variability than found in previous infrared (lower altitude, cloudtop) studies. Strong global variability on a 1–2 month timescale is clear and unambiguous. A limited number of excellent s/n measurements tentatively indicate the 1–2 month variability manifests most rapidly as change in the lower mesosphere, and more slowly as change in the upper mesosphere. Neither long term (1998–2004) nor diurnal variability in 65–100 km H2O is evident. While six-year and/or diurnal variabilities are not ruled out, they are weaker than the 1–2 month timescale variation. These conclusions are supported by initial (2004) sub-mm measurements.
Experiences with a Markov model for structural systems with time variant member resistances

Abstract The development and use of a Markov model for estimating the lifetime reliability of structural systems is presented. System failure is assumed to be the occurrence of adjacent member failures. The model was developed to allow the inclusion of time-variant member resistances. The use of the model is discussed for wood structural systems.
TGF-β1 stimulates production of gelatinase (MMP-9), collagenases (MMP-1, -13) and stromelysins (MMP-3, -10, -11) by human corneal epithelial cells

Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of ocular surface diseases. This study investigated the regulated expression of gelatinases (MMP-2 and -9), collagenases (MMP-1 and -13) and stromelysins (MMP-3, -10, and -11) by TGF-beta1 in cultured human corneal epithelial cells. Primary human corneal epithelial cell cultures were grown to confluence and treated with different concentrations (0.1, 1.0, 10 ng ml(-1)) of TGF-beta1 in serum-free medium for 6-24 hr. Total RNA was isolated from cultured cells with or without TGF-beta1 treatment for 6 hr and subjected to semi-quantitative RT-PCR and Northern hybridization. Conditioned media were collected from cultures with or without TGF-beta1 treatment for 24 hr to evaluate the MMP production by ELISA and activity assays. Semi-quantitative RT-PCR revealed that the expressions of MMP-9, -1, -13, -3, -10 and -11 mRNA were up-regulated by TGF-beta1 in a concentration-dependent fashion, while MMP-2 and MMP-14 production did not change. Northern hybridization confirmed these findings. Gelatin zymography, MMP ELISA and activity assays showed concentration-dependent stimulated production and activity of MMP-9, -1, -13, -3 and -10 protein in the conditioned media of cultures treated for 24 hr with TGF-beta1. In conclusion, our results demonstrate that TGF-beta1 stimulates the expression and production of gelatinase (MMP-9), collagenases (MMP-1, -13) and stromelysins (MMP-3, -10, -11) in human corneal epithelial cells. These findings suggest that TGF-beta1 may play a role in the pathogenesis of MMP mediated ocular surface diseases, such as sterile corneal ulceration.
BMPRIA is a promising marker for evaluating ganglion cells in the enteric nervous system--a pilot study

Congenital disorders of the enteric nervous system (ENS) comprise a large group of conditions characterized by abnormalities in the number, size, or location of enteric ganglia. Their diagnosis requires careful histological evaluation of intestinal biopsies to determine the presence and morphology of these cells. Based on the recently discovered role of bone morphogenetic proteins (BMPs) in ENS development, we examined the expression of the ligands, BMP2 and BMP4, and their receptors, BMPRIA, BMPRIB, and BMPRII, during formation of the human ENS. The spatiotemporal expression pattern of these proteins suggests a role for BMP signaling in human ENS formation. We find BMPRIA, in particular, strongly and specifically expressed in all ganglion cells of the ENS at every age examined, from fetus to adult. Moreover, BMPRIA immunohistochemistry consistently allowed the identification of ganglion cells in rectal biopsies from patients with Hirschsprung disease, intestinal neuronal dysplasia, and immature ganglion cells. We propose that BMPRIA immunohistochemistry may be a promising new tool for the identification of enteric ganglion cells in the evaluation of patients with neurointestinal disorders.
Clinical utility of exercise, pacing, and pharmacologic stress testing for the noninvasive determination of myocardial contractility and reserve☆

Abstract The ability of the left ventricle to modulate its performance is an important and integral component in the cardiovascular system's adaptive response to increased workload. Abnormalities in ventricular contractility can blunt this response and thus significantly limit the patient's functional capacity. The accurate determination and quantitation of cardiac contractility and reserve is a difficult task in the symmetrically contracting ventricle and more so when regional contraction abnormalities are present. Moreover, derangements in other physiologic varlables, such as ventricular loading conditions, heart rate, systemic vascular tone, cardiac autonomic function, and pulmonary gas exchange, can diminish cardiopulmonary reserve. This report relates the determinants of myocardial oxygen demand and efficiency to the currently avallable forms of exercise, pacing, and pharmacologic stress testing. Within this framework, commonly used as well as newer approaches to the noninvasive assessment of stress-induced changes in left ventricular performance and contractility are addressed. In addition, several examples are presented in which noninvasive techniques for assessing intracardiac structures, pressures, and flows (eg, echo/Doppler, radionuclide angiography, rapid acquisition computed tomography, and magnetic resonance imaging) are combined with various cardiovascular stress tests to achieve more reliable measures of myocardial contractility and reserve.
Optimization of feeding schedules in salmon hatcheries

A methodology is developed that determines feeding schedules which will reduce total food consumption for coho salmon in a hatchery during the rearing period. The method presented assumes that the feeding level has a parabolic mathematical form with respect to time. Coefficients of this parabola are converged upon in such a way that the fish achieve a particular size on a chosen release date and simultaneously total food consump tion for the rearing period is minimized. The indicator of feeding level chosen is a nondimensional parameter that equals one at the minimum feeding rate resulting in maximum growth rate and equals zero at a feeding rate that results in a zero growth rate. Results show that for long rearing periods corresponding to rearing in unheated water, the feeding level should be low initially and gradually increase towards the end of the rearing period. Conversely, for rearing periods simulating the accelerated growth periods that occur in heated hatcheries, feeding levels should in general...
Smart earthquake-resistant materials: using time-released adhesives for damping, stiffening, and deflection control

Preventing buildings and bridges from damage from severe dynamic loading events is a primary goal of civil infrastructure. Present designs attempt to control structural response by making the structures more massive, by increasing lateral stiffness through bracing, and by damping technology such as mass damping and base-isolation. These attempts affect portions of the governing equation: for an idealized building frame or bridge, the free vibrational behavior is described by Mu + cu + ku equals -mug(t) where m equals mass, c equals damping coefficient, k equals lateral stiffness, u equals deflection, and ug(t) equals ground acceleration. The use of adhesive released internally in a material based way of addressing the problem. The time release of low modulus adhesive chemicals would assist the damping characteristics of the structure, use of a stiffer adhesive would allow the damaged structure to regain some lateral stiffness (k) and adjustment of the set times of the adhesives would act to control the deflection. These can be thought of as potential new method of controlling vibration of behavior in case of a dynamic loading event. In past experiments, self-healing concrete matrices were shown to increase post-yield deflection and load carrying capability by the release and setting of adhesives. The results were promising in resisting damage of dynamic loads applied to frames. This indicates that self-healing concrete would be extremely valuable in civil engineering structures that were subjected to failure-inducing loads such as earthquakes.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Strength of scopolamine-induced amnesia as a function of time between training and testing

Variations in the strength of scopolamine-induced amnesia as a function of age of the habit were studied in Swiss Webster mice. Animals were trained in an active avoidance task to a criterion of 9/10 avoidances and immediately following training injected with scopolamine hydrochloride (1.0 mg/kg) or saline. Retention of the avoidance learning was evaluated by testing different groups of animals 1, 3, 7, 10, 14, and 28 days following training. The retention test consisted of five trials in which the CS but not the UCS was presented. Results indicated that saline-treated mice exhibited near-perfect retention up to 14 days post-training with forgetting beginning to be apparent at 28 days. Scopolamine treatment produced strong amnesia in animals tested 1 and 3 days post-training but normal retention in animals tested 7 and 10 days after learning. The amnesia abruptly reappeared at 14 days after which time it remained stable. The marked similarity of the scopolamine retention curve to changes in the strength of memory of discrimination learning in undertrained rats reported by Deutsch suggested that scopolamine resulted in the storage of a weak memory of the avoidance response. To explore this idea further we trained mice to a criterion (4/5) which would result in a weak avoidance response and tested different groups 1, 3, 10, 14, and 28 days following learning. Results showed that strength of the memory of avoidance learning increased up to 10 days and then decreased abruptly at 14 days thus replicating the general shape of the retention curve produced by injecting scopolamine following strong training. These data suggest that scopolamine disrupts processes essential for the formation of durable memories.
Parasitism of Iron-siderophore Receptors of Escherichia Coli by the Siderophore-peptide Microcin E492m and its Unmodified Counterpart

Microcin E492 (MccE492) is an antibacterial peptide naturally secreted by Klebsiella pneumoniae RYC492. Initially described as an 84-residue unmodified peptide, it was also recently isolated in a posttranslationally modified form, MccE492m. The production of MccE492m is dependent on the synthesis of enterobactin and the mceABCDEFGHIJ gene cluster. The posttranslational modification was characterized as a trimer of N-(2,3-dihydroxybenzoyl)-l-serine (DHBS) linked to the Ser84-carboxylate via a β-d-glucose moiety. MccE492m was shown to bind ferric ions through the trimer of DHBS. This is the first example of a novel type of antibacterial peptide termed siderophore-peptide. Recognition of MccE492m, but also of the unmodified MccE492, was shown to be mediated by the catecholate siderophore receptors FepA, Cir and Fiu at the outer membrane of E. coli. The siderophore-type modification was shown to be responsible for a significant enhancement of the microcin antibacterial activity. Therefore, we propose that MccE492 and MccE492m use iron-siderophore receptors for uptake into the target bacteria and that improvement of MccE492 antimicrobial activity upon modification results from an increase in the microcin/receptor affinity.
Design and implementation of a wireless medical system prototype for implantable applications

The design, implementation and testing of a wireless medical system (WMS) for continuous monitoring of biological parameters are presented in this paper. Special emphasis has been made on the implantable unit prototype. The proposed system consists of three main sections: implantable medical device (IMD), base station (BS) and graphical user interface. The IMD and BS communicate through an RF link that operates in both the industrial, scientific and medical (ISM, at 2.4---2.48 GHz) and the medical implantable communication service (MICS, at 402---405 MHz) bands. The IMD and BS are based on two commercially-available ultra-low power integrated circuits: a mixed-signal microcontroller and a medical implantable radio transceiver. A comprehensive explanation of the main design issues and implementation challenges is presented. The details regarding the analog front-end functionality, a low-power-oriented algorithm, an analysis of power consumption versus lifetime and a customized operating mode for power optimization are explained. The main considerations for link budget calculations in implantable applications are discussed. A test bench designed to emulate real conditions is used to verify the functionality of the WMS showing successful communication up to 2.1 m range with a data rate of 200 Kbps. The IMD works from a 3 V power supply with an average current consumption of 0.572 mA (including RF transmission) in continuous operation. This allows a 2 year IMD lifetime in periodic operation (for a 350 mAh battery), delivering 1 h of information per day.
Positron Emission Tomography/Computerized Tomography (PET/CT) Scanning for Preoperative Staging of Patients With Oral/Head and Neck Cancer

Purpose To investigate the role of 18-fluorine-fluorodeoxyglucose positron emission tomography/computerized tomography ( 18 F-FDG PET/CT) in the preoperative prediction of the presence and extent of neck disease in patients with oral/head and neck cancer. Patients and Methods Seventy patients were enrolled in the study, 47 of whom had a clinically negative neck (N0), 19 of whom had a clinically positive unilateral neck (N+), and 4 of whom were negative on 1 side of the neck and positive on the other. Each patient underwent a PET/CT study before undergoing selective neck dissection for N0 disease or modified radical neck dissection for N+ disease. Tissues were submitted for histopathologic examination and were oriented for the pathologist as to the oncologic levels so as to permit correlation between histopathologic findings and the imaging results. Results The sensitivity and specificity of the PET/CT procedure were 79% and 82% for the N0 neck, and 95% and 25% for the N+ neck. One hundred ninety-two (11.4%) of the 1,678 nodes identified at histopathology were positive for metastases. The overall nodal sensitivity and specificity were 48% and 99%, respectively. Conclusion In patients with clinically negative necks, a negative test would not help the surgeon in the management strategy of the patient because of the rate of false-negative results, but a positive test can diagnose metastatic deposits with a high positive predictive value. In patients with clinically positive necks, a positive test will confirm the presence of disease, although false-negative lymph nodes were additionally identified in these clinically positive necks. With respect to nodes, the sensitivity of the imaging procedure is such that the results could not help the surgeon in deciding which level to dissect and which to spare. In the final analysis, the head and neck oncologic surgeon should not depend on the results of the PET/CT scan to determine which patients will benefit from neck dissection. Rather, time-honored principles of neck surgery should be followed, particularly with regard to the liberal execution of prophylactic neck dissections in patients with clinically N0 necks.
A random map implementation of implicit filters

Implicit particle filters for data assimilation generate high-probability samples by representing each particle location as a separate function of a common reference variable. This representation requires that a certain underdetermined equation be solved for each particle and at each time an observation becomes available. We present a new implementation of implicit filters in which we find the solution of the equation via a random map. As examples, we assimilate data for a stochastically driven Lorenz system with sparse observations and for a stochastic Kuramoto-Sivashinsky equation with observations that are sparse in both space and time.
Dialectical materialism and political theology: Two views of the future

In a wide variety of publications,1 Johannes B. Metz programatically represented a new political theology of subject, society, history, and future. This theology participates intensely in the lively, ongoing discourse on the political and theological actuality and significance of the critical theory of society, religion and future set forth by the Marxist, Walter Benjamin.2 The purpose of this study is to illuminate several connections between Benjamin's critical theory and Metz's political theology, particularly with respect to the present stage of development in advanced capitalistic society and to their future.
A New FronTIR in Targeted Protein Degradation and Plant Development

Three papers, two in a recent issue of Nature and one in the July issue of Developmental Cell, identify a family of F box proteins as the long-sought receptors for the plant growth hormone auxin. The new studies reveal that auxin, a small molecule, regulates F box proteins, which are involved in ubiquitin-mediated protein degradation. This finding has profound implications for understanding plant physiology and development and for defining new modes of regulation of SCF ubiquitin ligase complexes.
STRUCTURE AND PROPERTIES OF HETEROMETALLIC ALKOXIDES CONTAINING COPPER(I)

Abstract The heterometallic Cu I alkoxides Li 4 Cu 4 (OCMe 3 ) 8 ( 1 ) and Ba 2 Cu 4 (OCEt 3 ) 8 ( 3 ) were synthesized from the component single metal alkoxides in anhydrous THF solution. Only 1 sublimes without decomposition under vacuum (150°C); 3 is non-volatile. Crystal structures were determined for 1, 3 and the previously reported Na 4 Cu 4 (OCEt 3 ) 8 ( 2 ). Compounds 1 and 2 have nearly identical M 4 Cu 4 O 8 cores consisting of two puckered M 2 O 2 rings related by a centre of symmetry and joined at the oxygens by two bridging copper atoms, and at the M edges by two nearly linear OCuO units. Compound 3 has a Ba 2 (OR) 2 ring containing the centre of symmetry and is bridged by two Cu 2 (OR) 3 units that are nearly perpendicular to the Ba 2 O 2 ring. The two BaCu 2 O 3 planes in 3 are parallel, but separated by 0.48 A. Hydrolysis of compounds 1–3 in THF afforded an orange or orange-brown solid that was converted to the mixed metal oxide by thermolysis, but copper and Cu 2 O were also produced from the Li 4 Cu 4 (OCMe 3 ) 8 hydrolysis product.