cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma

Background This pilot project was undertaken to evaluate the toxicity of and tumor response to combined 131I anti-carcinoembryonic antigen monoclonal antibody (131I anti-CEA RMoAb) and hyperthermia in patients with metastatic colorectal adenocarcinoma. Methods Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact 131I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperthermia, were the basis of this study. The first three patients were treated with 30 mCi/m2 of 131I anti-CEA RMoAb, and the next three received 60 mCi/m2. Pharmacokinetic clearance data were reported for all nine patients. Results Thermometry data revealed an average T90 of 40.3 (+/- 1.4 degrees C) and T50 of 41.1 (+/- 1.2 degrees C). The average thermal dose equivalent at 42.5 degrees C was 34.5 (+/- 21.5) minutes. The average Tmin, Tmax, and Tmeam were 40 (+/- 1.2 degrees C), 42.4 (+/- 0.7 degrees C), and 41.1 (+/- 1.1 degrees C), respectively. The pharmacokinetic clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. Conclusions It is feasible to combine hyperthermia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperthermia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combined modality in the management of maligancies.
Improved parameter fitting for models of young and aged neurons

The parameters of neuronal compartment models must be determined carefully in order to match experimental data. Optimization algorithms can simplify this task by automatically searching the multidimensional parameter space to identify combinations of parameters that best fit experimental data, as measured by a fitness function that represents salient differences between simulated and experimental data. The success of automated parameter fitting depends critically on many issues, including the choice of parameters selected for fitting, the parameter search method, and the design of the fitness function. Previously we developed a fitness function that explicitly quantifies the shape of action potentials and afterhyperpolarizations [1], and the time-varying firing rate [2]. The present project arises from our study of neocortical pyramidal cells from young and aged rhesus monkeys in vitro [3]. In response to current clamp protocols that evoked action potentials, aged neurons fired at significantly higher rates than young ones did. Yet, both young and aged neurons displayed an initial fast phase of firing rate adaptation followed by a slower one. Neither parameter optimization with our existing fitness function, nor the popular phase-plane method [4], sufficiently captured the two-phase adaptation. We have extended our fitness function to fit firing rate time series with two single exponentials, separated by an automatically-chosen cutoff. The fitness function also includes a term to quantify action potential backpropagation, whereby voltage decays approximately exponentially with distance from the soma [5]. The fitness function is designed for use with NEURON, with the parameter search guided by MATLAB’s Global Optimization Toolbox. We used the fitness function and search method to optimize morphologically accurate compartmental models of young and aged neurons to their respective physiological data. We compared results from our original and improved fitness functions against the phase-plane fitness function, separately optimizing either ion channel densities or channel kinetics. All searches identified multiple combinations of parameters that fit the data, with our new fitness function having the best qualitative matches to empirical data. These parameter fits will be used to identify biological mechanisms that may be responsible for the physiological differences between young and aged neurons.
Magnetostratigraphy of Early Cretaceous Maiolica sections of the Southern Alps (Cismon and Pra da Stua, Italy)

SUMMARY The bottom part of the Cretaceous Cismon section in the Southern Alps was sampled for high-resolution magnetostratigraphy. Although the almost pure pelagic nannofossil limestones (c. 90 per cent CaCO,) of the Maiolica/Biancone Formation are extremely weakly magnetized, stepwise thermal and alternating-field demagnetization removed overprints and isolated a characteristic remanent magnetization which is interpreted as a primary magnetization. The dominant magnetic carrier mineral is magnetite; a small fraction of haematite may be present. A clear reversal pattern can be correlated unambiguously with Mesozoic polarity chrons CMlON to CM8. A less wellconstrained magnetostratigraphy from the Pra da Stua section could not be directly correlated with the global polarity scale, but biostratigraphic information allows its assignment to the interval CM10-CM5. A counterclockwise rotation of 56" and a northward translation of 28" latitude for the Cismon locality since the Early Cretaceous are derived from the palaeomagnetic data, consistent with previous results from the Southern Alps. The high-resolution magnetostratigraphy of the Cismon section is used in an effort to refine the Cretaceous timescale by the combination of magnetostratigraphic and cyclostratigraphic results from the same section. The cyclostratigraphic duration estimates of chrons CMlON to CM8 are compared to their equivalents in a number of traditional timescales and found to be shorter by a factor of 1.26-2.58.
UCLA Community College Review: Community College Scholarship and Discourse:

This review discusses the concept of the two-year college as a separate discourse community within the larger discourse community of higher education. The article offers a complete definition and description of discourse communities and discusses a new understanding of scholarship in terms of the scholarship of teaching. The review argues that redefining community college scholarship to include teaching as a form of scholarship will build a bridge for community college professionals to assert their knowledge and power within higher education.
On the Incongruence of Theory and Practice in behavior Research: what can and should be done about it

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen, The medical sciences are mutually interdependent. Progress in one field is often closely associated with development in others….It is not always such progress, as immediately are useful and of benefit, which should be considered as especially important; this character can also be attributed to those which are themselves less spectacular but form the basis for others which are then only a further development of it.
Hospital Staff Registered Nurses’ Perception of Horizontal Violence, Peer Relationships, and the Quality and Safety of Patient Care

Objective To test hypotheses from a horizontal violence and quality and safety of patient care model: horizontal violence (negative behavior among peers) is inversely related to peer relations, quality of care and it is positively related to errors and adverse events. Additionally, the association between horizontal violence, peer relations, quality of care, errors and adverse events, and nurse and work characteristics were determined. Participants A random sample (n= 175) of hospital staff Registered Nurses working in California. Methods Nurses participated via survey. Bivariate and multivariate analyses tested the study hypotheses. Results Hypotheses were supported. Horizontal violence was inversely related to peer relations and quality of care, and positively related to errors and adverse events. Including peer relations in the analyses altered the relationship between horizontal violence and quality of care but not between horizontal violence, errors and adverse events. Nurse and hospital characteristics were not related to other variables. Clinical area contributed significantly in predicting the quality of care, errors and adverse events but not peer relationships. Conclusions Horizontal violence affects peer relationships and the quality and safety of patient care as perceived by participating nurses. Supportive peer relationships are important to mitigate the impact of horizontal violence on quality of care.
Steady incompressible flow past a row of circular cylinders

Numerical solutions are presented for steady two-dimensional incompressible flow past an infinite row of cylinders (of unit radii, with distances W between their centres). The calculations cover R [les ] 700 for 5 [les ] W [les ] ∞ and also R = 800 for 5 [les ] W [les ] 100 (where R denotes the Reynolds number based on the cylinder diameters). The recirculation regions (wake bubbles) are found to grow in length approximately linearly with R in all cases. For high values of R, a major change occurs in their character when W is increased past Wcrit ≈ 16. While they have remained slender up to this point (essentially only stretching in length in proportion to R), their centres of circulation have moved towards their ends. As W is further increased, the wake bubbles widen rapidly, beginning from the rear of the wakes. In the limit of W→∞, the present results agree with the previous ones for a single cylinder as reported by Fornberg (1985).
Determination of glucose concentrations in an aqueous matrix from NIR spectra using optimal time-domain filtering and partial least-squares regression

The authors have investigated the use of a time-domain optimal filtering method to simultaneously minimize both the baseline variation and high-frequency noise in near-infrared (NIR) spectrophotometric absorption data of glucose dissolved in a simple aqueous (deionized water) matrix. By coupling a third-order (6-pole) digital Butterworth bandpass filter with partial least-squares (PLS) regression modeling, glucose concentrations were determined for a set of test data with a standard error of prediction (SEP) of 10.53 mg/dl (mean percent error: 4.24%) using 7 PLS factors. Compared to the unfiltered test data for 6 PLS factors and a SEP=17.00 (mean percent error: 7.38%) this results shows more than a 38% decrease in the error. The glucose concentrations ranged from 51 mg/dl to 493 mg/dl, and the NIR spectral region between 2088 nm and 2354 nm (4789 cm/sup -1/ and 4248 cm/sup -1/) was used to develop the optimal PLS model. The optimal PLS model was determined from a sequence of 3-dimensional performance response maps for different numbers of PLS factors (2-10). A total of 99 NIR spectra were generated for glucose dissolved in deionized water using a NIRsystems 5000 dispersive spectrophotometer. Nine of these spectra were generated for only water, which were averaged and subtracted from the remaining 90 spectra to generate the training and test data sets, thereby, removing the intrinsic high background absorption due to the water. The training set consisted of 57 spectra and associated glucose concentration target values, and the test set was comprised of the remaining 33 spectra and target values. Performance results were compared for 3 different digital Butterworth bandpass filters (4-poles, 6-poles, and 8-poles), and a digital Gaussian filter design approach (i.e., Fourier filtering).
Convergence of infinite dimensional sampled LQR problems: theory and numerical results

A theory for convergence of the closed-loop solution to infinite-dimensional discrete-time linear quadratic regulator (LQR) problems on the infinite time interval to the solution of a corresponding continuous-time LQR problem as the length of the sampling interval tends toward zero is discussed. Convergence of solutions to the operator algebraic Riccati equation and corresponding optimal feedback control gains is guaranteed under appropriate uniform stabilizability and detectability conditions and consistent sampling. Some numerical results involving the optimal LQ control of a heat or diffusion equation, a hereditary or delay differential equation, and a hybrid system of ordinary and partial differential equations describing the transverse vibration of a cantilevered Voigt-Kelvin viscoelastic beam with tip mass are also presented. >
The Effects of Grouping Practices and Curricular Adjustments on Achievement

N = 645) was used in this study. achievement data were collected using a curriculum-based assess ment. repeated measures analysis of variance was employed to investigate the effects of grouping arrangements and curricular design on the treatment and comparison group posttest scores. results indicated significant differences, f (5, 246) = 22.618, p <. 001, between comparison and revision treatment groups on the posttest after adjusting for grade level (4 or 5). further results indicated significant differences, f (11, 673) = 41.548, p <. 001, among all treatment groups after adjusting for grade level.
A multi-element monolithic mass flowmeter with on-chip CMOS readout electronics

The implementation of control circuitry is presented for a multielement mass flow sensor capable of simultaneously measuring five different gas-related parameters necessary for mass flow. A process has been developed to merge the micromachined sensing structures and the CMOS readout circuitry on a single chip. The total process requires thirteen masks: eight for the double-poly, single-metal CMOS process and five for additional processing of the transducer elements. The on-chip circuitry includes offset-free instrumentation amplifiers, an analog multiplexer, heater drive circuits, self-test circuitry and a bandgap temperature sensor using substrate n-p-n bipolar transistors. The resulting multielement chip requires only ten external pins and delivers high-level buffered output signals describing gas velocity, type, direction, pressure and temperature. >
Revisiting dirt cracking as a physical weathering process in warm deserts

Abstract A half century ago C.D. Ollier proposed that insolation-driven temperature changes expand and contract fill in fissures enough to widen cracks, a process that would permit progressively deeper penetration of fissure fills, that would in turn generate a positive feedback of greater and greater strain until desert boulders and bedrock shatters. Although desert physical weathering by “dirt cracking” has occasionally been cited, this hypothesized process remains without support from subsequent research. Here, field observations, electron microscopy, X-ray powder diffraction, particle-size analysis, and laboratory experiments shed new light on dirt cracking. Little clear evidence supports the original notion of expansive pressures from thermal fluctuations. However, mineralogical, high resolution transmission electron microscopy, back-scattered electron microscopy, and experimental evidence support two alternative processes of widening fractures: wetting and drying of fills inside fissures; and the precipitation and remobilization of calcium carbonate. A re-envisioned dirt-cracking wedging process starts with calcium carbonate precipitating in fissures less than 5 μm wide. First precipitation, and then ongoing dissolution of this laminar calcrete, opens enough space for dust to penetrate into these narrow fractures. Wetting of expansive clays in the fissure fill exerts enough pressure to widen and deepen the fissure, allowing the carbonate precipitation process to penetrate even deeper and allowing even more dust to move into a fracture. As the dust infiltrates, its texture changes from a chaotic mix of particles to an alignment of clays parallel to fissure sides. This parallel alignment could increase the efficiency of fill wedging. Ollier's concept of a positive feedback remains supported; each increment of fracture deepening and widening permits more, even deeper infiltration of laminar calcrete and dust. Field and electron microscope observations of rock spalling in the winter of 2010 are consistent with Ollier's hypothesis that dirt cracking is a common physical weathering process in deserts that splits rocks of all different sizes.
Eliminating spurious lipid sidebands in 1H MRS of breast lesions

Detecting metabolites in breast lesions by in vivo 1H MR spectroscopy can be difficult due to the abundance of mobile lipids in the breast which can produce spurious sidebands that interfere with the metabolite signals. Two-dimensional J-resolved spectroscopy has been demonstrated in the brain as a means to eliminate these artifacts from a large water signal; coherent sidebands are resolved at their natural frequencies, leaving the noncoupled metabolite resonances in the zero-frequency trace of the 2D spectrum. This work demonstrates that using the zero-frequency trace—or equivalently the average of spectra acquired with different echo times—can be used to separate noncoupled metabolite signals from the lipid-induced sidebands. This technique is demonstrated with simulations, phantom studies, and in several breast lesions. Compared to the conventional approach using a single echo time, echo time averaging provides increased sensitivity for the study of small and irregularly shaped lesions. Magn Reson Med 48:215–222, 2002. © 2002 Wiley-Liss, Inc.
Cognitive impairment in patients with multiple sclerosis: association with the APOE gene and promoter polymorphisms.

Background Studies examining the e4 allele of the APOE gene as a factor affecting the severity of multiple sclerosis (MS) have yielded conflicting results. The focus of these studies on physical disability to the neglect of cognitive impairment is surprising in light of the associations between the e4 allele and other dementia conditions. Only two studies examine the relationship between the e4 allele and cognitive impairment.Methods A neuropsychological test battery was administered to 263 MS patients, and their current disability status was evaluated. Genotypes were determined for APOE epsilon and for two promoter region polymorphisms (-219 G/T and -491 A/T).Results Although effects were generally weak, female patients with the -491 AA genotype had a later age of disease onset, lower disability scores, and somewhat higher scores on the cognitive battery. Male patients with the e2 allele had lower disability and higher scores on the cognitive battery. The e4 allele was not related to physical disability,...
Neurodevelopmental Dysfunction and Specific Learning Disabilities in School-Aged Twins

The frequency of the developmental dysfunction and specific learning disabilities were assessed in the retrospective study in the group of 56 school-aged twins. The relationships between genetic, perinatal and social factors and learning disability were also determined. It was found that 12.5% of twins had learning disabilities. The most common neurodevelopmental dysfunction were language disorders, poor graphomotor fluency and poor fine motor dexterity. It was also found that educational difficulty were associated with prematurity, low Apgar scores, neonatal complications and familial predisposition.
Modeling of approximated electron transport across ion beam patterned quantum dot nanostructures

High energy ion beams are used to modify co-deposited nanolayer films of alternated materials (e.g. insulator and metal, two different semiconductors, even more complex arrangements) to form nanodots through localized nucleation. The particular application being considered here is for high efficiency thermoelectric conversion systems. The performance of a thermoelectric converter is generally given by the figure of merit, ZT, which is a function of the Seebeck coefficient, electrical conductivity, and thermal conductivity. A high performance device would have a maximized electrical conductivity and a minimized thermal conductivity (maximum electron transport, minimal phonon transport). The current models of electron and phonon transportation through 1D, 2D, 3D quantum regimented structures assume an infinitely repetitive perfect structural “cell”, with complicated algorithms requiring intensive computing power. The main focus for this modeling effort is to reduce the three-dimensional problem to a single dimensional approximation without sacrificing the quality of the result. The nanostructure being investigated has Si and Ge quantum dots arranged with perfect periodicity in all three Cartesian directions, with the heat and electricity flow monitored in the z-direction (cross-plane as initially layered). Non-Equilibrium Green’s Functions Formalism (NEGF) is the mode for calculating the theoretical electrical properties assuming a one-dimensional quantum well arrangement in the z-direction (with finite boundaries in the x and y directions) with tight binding (nearest neighbor approximation). The results are to be compared with experimental measurements on such structures.
Low cost optical up-conversion of IR-UWB signals beyond the relaxation frequency of a vertical cavity surface emitting laser (VCSEL)

In this paper, we up-convert IR-UWB (Impulse Radio-Ultra Wide-Band) signals for transmission over single mode optical fiber systems. We use a low cost device, a single mode vertical cavity surface emitting laser (VCSEL) and demonstrate the feasibility to up-convert a monocycle (800 MHz - 2.5 GHz), while retaining a high resemblance, beyond the relaxation frequency of the laser diode up to around 12 GHz. A correlation figure of 0.94 is obtained between the emitted and received pulse.
Inherited Disorders of Connective Tissue

Marfan syndrome is an autosomal dominant disease characterized by pleiotropic manifestations involving the cardiovascular, ocular, and skeletal systems. The most common cardiovascular complication in patients with Marfan syndrome is progressive aortic root enlargement initially occurring at the sinuses of Valsalva. Some patients have dissections of the aorta, most often a type I dissection. Mitral valve prolapse is very common in these patients. The majority of patients with thoracic aortic aneurysms and dissections who have cystic medial necrosis of the aorta do not have Marfan syndrome. Ehlers-Danlos syndrome (EDS) is a heterogeneous group of disorders that are classified together on the basis of skin hyperextensibility, cutaneous fragility, joint laxity, dystrophic scarring, and easy bruising. Spontaneous arterial rupture occurs in type IV EDS. Supravalvular aortic stenosis is an autosomal dominant disorder caused by narrowing of the ascending aorta just distal to the coronary ostia. Pseudoxanthoma elasticum is an inherited disease caused by progressive calcification of elastic fibers in the connective tissue throughout the body.
Mechanisms of Insulin Resistance in Humans and Possible Links With Inflammation

Insulin resistance is a major player in the pathogenesis of the metabolic syndrome and type 2 diabetes, and yet, the mechanisms responsible for it remain poorly understood. Magnetic resonance spectroscopy studies in humans suggest that a defect in insulin-stimulated glucose transport in skeletal muscle is the primary metabolic abnormality in insulin-resistant type 2 diabetics. Fatty acids appear to cause this defect in glucose transport by inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1 associated phosphatidylinositol 3-kinase activity. A number of different metabolic abnormalities may increase intramyocellular/intrahepatic fatty acid metabolites; these include increased fat delivery to muscle/liver as a consequence of either excess energy intake or defects in adipocyte fat metabolism and acquired or inherited defects in mitochondrial fatty acid oxidation. Understanding the molecular/biochemical defects responsible for insulin resistance is beginning to unveil novel therapeutic targets for treatment of the metabolic syndrome and type 2 diabetes.
Computer Communications Software

The sections in this article are 1 Core Functionality and Implementation Techniques 2 The Internet Architecture 3 High-Level Communication Services 4 Optimizing Communication Software
Interframe video coding using adaptive sampling and classified vector quantization

The authors propose an adaptive sampling and vector quantization scheme to compress motion compensated differential images (MCDI). MCDI are adaptively sampled based on either their local spectral or geometrical characteristics. Various image decomposition schemes are proposed to design the nonuniform sampling patterns that are used in the sample selection process. The sampling structure can serve as a classifier to distinguish different features of the subimage regions, i.e., uniform, edge, etc. The set of vectors formed by the chosen samples associated with each distinct sampling pattern is used to generate a codebook for vector quantization (VQ), resulting in a classified multicodebook approach to VQ. This adaptive sampling and vector quantization scheme demonstrated superior performance over direct VQ in terms of both coding fidelity and computational efficiency. Simulation results have shown good coding fidelity at low bit rates: below 0.1 bits/sample with signal-to-noise ratio above 30 dB. >
Parkinson’s disease: clinical features and diagnosis

Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.
Children’s Self-Perceptions and Sources of Physical Competence Information: A Cluster Analysis

This study explored relationships among children’s age, individual differences, and sources of physical competence information. Children (N = 183) completed measures of competitive trait anxiety (CTA), perceived physical competence (PC), general self-esteem (SE), and sources of competence information in the sport domain. A cluster analysis revealed four distinct profiles of children. In Cluster 1, children were younger, scored relatively higher in CTA and lower in PC, and indicated strongest preference for pregame anxiety as a source of information. Cluster 2 was characterized by children with lower PC and SE scores who placed lower importance on parental evaluation and pre­ game anxiety sources. In Cluster 3, children scored higher on PC and SE, moderately lower on CTA, and preferred self-referenced and parental evaluation criteria. In Cluster 4, children were older, higher in CTA, lower in PC and SE, and indicated strongest preference for social comparison/evaluation criteria. The criteria children use ...
Vowel Hiatus and Faithfulness In Tohono O'Odham Reduplication

L'A. s'interesse au phenomene de reduplication et, particulierement, aux relations entre la base et l'element repete. La Theorie de l'Optimalite utilise la notion de contraintes de fidelite pour etablir des regles de regulations de ces relations. McCarthy et Prince (1999) ont avance deux modeles caracterisant la reduplication et les contraintes d'ordonnancement des affixes par rapport a la base : le Modele Basique et le Modele Integral. L'A. etudie la pertinence de ces modeles pour la description de la reduplication (accompagnee d'un phenomene de hiatus vocalique) en tohono o'odham (papago), une langue uto-aztec
THE IMPACT OF CONTINUING EDUCATION TRAINING ON LAW GUARDIAN KNOWLEDGE, EFFICACY, AND PRACTICE BEHAVIORS

There is an increased demand for law guardians in domestic violence cases, especially those involving child witnesses. Training is required for law guardians to meet child clients’ needs. While workshops and conferences are typical venues for continuing education training, their effectiveness is unknown. This pilot study compared law guardians who attended a conference on community violence and children to nonattendees on several training outcomes. Results showed a positive impact on attendees’ feelings of efficacy and intentions to carry out new practice behaviors post-conference; differences were maintained at follow-up. Limitations and implications of this pilot study are discussed.
Amplification of the gene for SCAP, coupled with Insig-1 deficiency, confers sterol resistance in mutant Chinese hamster ovary cells

The endoplasmic reticulum membrane proteins Insig-1 and Insig-2 limit cholesterol synthesis, in part through their sterol-dependent binding to sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP). This binding prevents proteolytic processing of SREBPs, membrane-bound transcription factors that enhance cholesterol synthesis. We report here the characterization of mutant Chinese hamster ovary (CHO) cells, designated SRD-19, that are resistant to 25-hydroxycholesterol, a potent inhibitor of SREBP processing. SRD-19 cells were produced by mutagenesis of Insig-1-deficient SRD-14 cells, followed by selection in high levels of 25-hydroxycholesterol. 25-Hydroxycholesterol fails to suppress SREBP processing in SRD-19, even though they express normal levels of Insig-2. The number of copies of the gene encoding SCAP was found to be increased by 4-fold in SRD-19 cells compared with wild-type CHO cells, leading to the overproduction of SCAP mRNA and protein. Our data indicate that overproduced SCAP saturates the remaining Insig-2 in SRD-19 cells, thus explaining their resistance to 25-hydroxycholesterol. Consistent with this conclusion, regulated SREBP processing is restored in SRD-19 cells upon transfection of plasmids encoding either Insig-1 or Insig-2. These results highlight the importance of SCAP/Insig ratios in normal sterol-regulated processing of SREBPs in cultured cells.
How not to learn: Reflections on Wittgenstein and learning

It is well known that when considering a particular concept, language game, or linguistic technique, Wittgenstein often asked “How would one teach this?” or “How is it learned?” What is not so often commented upon is that the latter question is frequently framed negatively: “Who would learn anything from this?” — and the implication is that no one could learn anything from the reported remark.
Effect of early gestational undernutrition on angiogenic factor expression and vascularity in the bovine placentome

The effect of early gestation maternal undernutrition followed by realimentation on placento- mal vascular growth and angiogenic factor expression was determined in multiparous beef cows bred to the same bull. Cows gestating only female fetuses (n = 30) were fed in equal numbers to meet the NRC require- ments (control) or were fed below the NRC require- ments to lose BW (nutrient restricted; NR) from d 30 to 125 of gestation. After slaughter on d 125 of gestation, 10 control and 10 NR cows were necropsied. The re- maining NR cows (n = 5) were then fed to achieve a BCS equal to their control group contemporaries (n = 5) by d 220 of gestation. All cows were fed the control diet from d 220 until 250 of gestation, when the re- maining control and NR cows were slaughtered and necropsied. At necropsy, placentomes were fixed via perfusion of the caruncular and cotyledonary arteries to determine capillary vascular density. Cotyledonary (fetal placental) and caruncular (maternal placental) tissues also were snap-frozen in liquid nitrogen, and mRNA concentrations of vascular endothelial growth
Pericyte chemomechanics and the angiogenic switch: insights into the pathogenesis of proliferative diabetic retinopathy?

Purpose To establish the regulatory roles that pericytes have in coordinating retinal endothelial cell (EC) growth and angiogenic potential. Methods Pericytes were derived from donor diabetic (DHuRP) or normal (NHuRP) human retinae, and characterized using vascular markers, coculture, contraction, morphogenesis, and proliferation assays. To investigate capillary "cross-talk," pericyte-endothelial coculture growth, and connexin-43 (Cx43) expression assays were performed. Paracrine effects were examined via treating EC with pericyte-derived conditioned media (CM) in proliferation, angiogenesis, and angiocrine assays. The effects of sphingosine 1-phosphate (S1P) were assessed using receptor antagonists. Results The DHuRP exhibit unique proliferative and morphologic properties, reflecting distinctive cytoskeletal and isoactin expression patterns. Unlike NHuRP, DHuRP are unable to sustain EC growth arrest in coculture and display reduced Cx43 expression. Further, CM from DHuRP (DPCM) markedly stimulates EC proliferation and tube formation. Treatment with S1P receptor antagonists mitigates DPCM growth-promotion in EC and S1P-mediated pericyte contraction. Angiocrine assays on normal and diabetic pericyte secretomes reveal factors involved in angiogenic control, inflammation, and metabolism. Conclusions Effects from the diabetic microenvironment appear sustainable in cell culture: pericytes derived from diabetic donor eyes seemingly possess a "metabolic memory" in vitro, which may be linked to original donor health status. Diabetes- and pericyte-dependent effects on EC growth and angiogenesis may reflect alterations in bioactive lipid, angiocrine, and chemomechanical signaling. Altogether, our results suggest that diabetes alters pericyte contractile phenotype and cytoskeletal signaling, which ultimately may serve as a key, initiating event required for retinal endothelial reproliferation, angiogenic activation, and the pathological neovascularization accompanying proliferative diabetic retinopathy.
Echo Chambers, Lions' Dens, and Networks: Matching in Political Information Markets

I consider the role of the media in transmitting information about competing candidates or policies to voters. Information suppliers in the media ("pundits") may be matched to voters of their own preference-type "echo chambers"), voters of the opposite preference-type ("lions' dens"), or multiple types of voters ("networks"). I show that: a.) pundits in lion's dens and minority-type pundits on networks convey no useful information, and where they exist, they must serve primarily as entertainers, as foils for other pundits, or for some other non-informational purpose; b.) language used by pundits in echo chambers will typically be characterized by high degrees of inflammatory humor, rhetoric, and demagoguery relative to networks; c.) when a variety of media exist, media consumption by voters will tend to be separated across preference-types; and d.) echo chamber pundits are vital to the informational structure of the market, and a decrease in minority-type echo chambers may diminish the truthfulness of all pundits.
Surveillance, Consumers, and Virtual Worlds

This is a brief essay, we call "think-pieces", designed to stimulate a discussion on a particular topic. For this series of essays we propose the following question: "Consumer behavior in virtual worlds, is it really any different to the real world, or is it simply a case of 'old wine in a new bottle'?"
Rights and Responsibilities of the American Business Corporation

Two issues dominate discussions about business corporations in the twenty-first century: corporate social responsibility and corporate participation in the political process. Each of these issues has roots that date back generations, and each has been the subject of heated controversy for almost as long. Despite the lengthy period of time in which they have been debated, and despite the current degree of interest in them, these two issues have not been examined collectively in legal scholarship. That is, discussions about corporate social responsibility ordinarily occur entirely separate from discussions about corporate participation in the political process. The two subject matters are treated as entirely distinct, with little substantive connection between them. This is mistaken. Any robust theory of corporate social responsibility must also address the question of corporate participation in the political process, and vice-versa. Moreover, I suggest that the two phenomena are, by nature, directly proportionate to one another. That is, the degree to which a corporation is deemed beholden to notions of corporate social responsibility ought to correlate to the cognizable rights that the corporation possesses. For each phenomenon helps to delineate the role of the corporation in our society – and in parallel fashion.
Hospitalizations at Nonfederal Facilities for Lower Respiratory Tract Infection in American Indian and Alaska Native Children Younger than 5 Years of Age, 1997-2012.

Objectives To evaluate hospitalizations at nonfederal facilities for lower respiratory tract infection (LRTI) in American Indian/Alaska Native (AI/AN) children and to compare associated rates and risk factors in AI/AN children and white children. Study design We used Kids' Inpatient Database samples from 1997-2012 to identify discharges in non-Hispanic AI/AN and white children ages Results During the study period, LRTI-associated discharge rates (per 1000) declined for white children (from 14.8 to 10.9; P P = .35 for trend). Discharges in AI/AN children were associated with low household income, Medicaid insurance, and rural residence. In a case-cohort analysis of infants hospitalized with LRTI in 2012, discharge rates were higher for AI/AN infants than for white infants only in the West (72.8 vs 22.2; aOR, 2.5; 95% CI, 1.8-3.4). Conclusions Among young children who use nonfederal hospitals, LRTI-associated hospitalizations occur at substantially higher rates for AI/AN children than for white children. These hospitalizations occur at rates that are particularly high for AI/AN infants in the West, where rates are comparable with those reported for Indian Health Service enrollees.
The Generality of Theory and the Specificity of Social Behavior: Contrasting Experimental and Hermeneutic Social Science

Since its inception, experimental social psychology has arguably been of two minds about the nature and role of theory. Contemporary social psychology's experimental approach has been strongly informed by the “nomological-deductive” approach of Carl Hempel in tandem with the “hypothetico-deducive” approach of Karl Popper. Social psychology's commitment to this hybrid model of science has produced at least two serious obstacles to more fruitful theorizing about human experience: (1) the problem of situational specificity, and (2) the manifest impossibility of formulating meaningful general laws of human social behavior. It is argued that a social psychology based on the search for this kind of lawfulness, under the auspices of either a strict or loose interpretation of the largely Hempelian model, is ultimately unworkable. An alternative approach to social psychology that is attentive both to the need for understanding individual situations and behaviors and to the need for generalized understanding of actual human behaviors is offered. This approach is grounded in the hermeneutic tradition.
Expandable Metal Stents for the Treatment of Cancerous Obstruction of the Gastrointestinal Tract

Expandable metal stents have been approved by the Food and Drug Administration for the treatment of gastrointestinal obstruction due to cancer. Although they have not been approved for use in benign disease, there are specific clinical indications for which expandable metal stents may be beneficial. This article reviews the uses of expandable metal stents for gastrointestinal obstruction due to cancer. General Concepts Gastrointestinal stents are placed by gastroenterologists under endoscopic guidance with the aid of fluoroscopy or by interventional radiologists using fluoroscopic guidance alone. Expandable metal stents are made of metal alloys and have varying shapes and sizes, depending on . . .
Effect of Working Time on Fatigue Condition of The Station Attendants on Duty along Jiaozhou-Xinyi Railway

[Objective]To understand the effect of the working time on fatigue condition of station attendants on duty,and provide basis for reasonable shifts and employment of railway transportation.[Methods]The physical fatigue factors changes of 117 station attendants on duty along Jiaozhou-Xinyi railway were investigated before working and after different working hours,the physical and psychological condition during working and the fatigue condition before and after working were evaluated.[Results]It can be seen from the testing indicators of the station attendants on duty before and after work that the items of head sank,headache,general malaise,yawn of the body factor,the items of rhembasmus,sedentariness,reticence of the mental factor,the items of eyes fatigue,eyes dry,not flexible,hypacusia and tinnitus of the nerve factor had significant differences.10 h working had more obvious impact on physical fatigue than 6h and 8h working.The items of choice reaction time,CFF,work capacity and short-term memory,etc in fatigue testing also had a difference before and after work,as well as error and missing deleting words and error rate.Fatigue condition of 10 h working was more serious than that of 6 and 8 h working.[Conclusion]The fatigue mainly causes by the long working time,monotonous work and heavy responsibility.Scientific arrangement of work,health education and intervention are the main means to ensure the physical health of station attendants on duty.
Use of display technologies for augmented reality enhancement

Augmented reality (AR) is seen as an important tool for the future of user interfaces as well as training applications. An important application area for AR is expected to be in the digitization of training and worker instructions used in the Brilliant Factory environment. The transition of work instructions methods from printed pages in a book or taped to a machine to virtual simulations is a long step with many challenges along the way. A variety of augmented reality tools are being explored today for industrial applications that range from simple programmable projections in the work space to 3D displays and head mounted gear. This paper will review where some of these tool are today and some of the pros and cons being considered for the future worker environment.
Monoaminergic innervation of the rat kidney: a quantitative study

The sympathetic innervation of the renal tubules and vasculature was characterized by measuring the overlap of accumulations of autoradiographic grains (AAGs) on these structures in autoradiograms of kidney sections from rats injected with tritiated norepinephrine. AAG overlap was used as an indirect measure of the innervation of those structures. The renal vasculature showed x 4.5 more AAG overlap than observed on renal tubules. The greatest amount of AAG overlap occurred on afferent arterioles, followed by efferent arterioles, interlobular arteries, cortical capillaries, arcuate arteries, and renal veins. High concentration of AAGs occurred along the vascular bundles of the outer stripe. In the tubular nephron the proximal tubule had the greatest amount of AAG overlap, followed by the cortical thick ascending limb of Henle, the connecting tubule, the distal convoluted tubule, and the collecting duct. It was found that afferent arterioles had significantly higher mean density of AAG overlap than efferent arterioles for the superficial, midcortical, and juxtamedullary (vascular bundles excluded) renal cortex. There was consistently more AAG perimeter facing the interstitium than overlapping the vasculature. These observations, together with the ultrastructural distribution of synaptic vesicles in varicosities, suggest that the interstitium might be an additional pathway of neurotransmitter access to the effector structures.
Historical perspectives on the epidemiology and ecology of mosquito-borne virus encephalitides in the United States.

This talk will be a sketchy history of the mosquito-borne virus encephalitides in the United States. I have tried to select those efforts and findings which have strongly influenced the course of development in this field. You should not be at all surprised to find William C. Reeves inextricably involved throughout. After all, he has worked on the virus encephalitides essentially all of his adult life. As an eminent investigator, leader, and teacher, he has in great part set the pace and been responsible for our present high state of knowledge in this area. The viruses to be considered are western equine encephalomyelitis (WEE), eastern equine encephalomyelitis (EEE), St. Louis encephalitis (SLE), and the California serogroup. I was tempted to include Venezuelan equine encephalitis (VEE) also, as it is a fascinating subject.
Letter to the Editor on ‘The urgency of annotating pathogen hypothetical genes’

Abstract Hypothetical genes, despite encompassing 25–50% of all coding genes of pathogenic bacteria have been under-investigated. For inherent obstacles in homology-based annotation, these genes have been relegated, which seems to have been a huge mistake in drug discovery pursuits. Among other factors, in vitro adaptation leads to radical shuffling of genome, and lack of ambient conditions prevent elaboration of several virulence-associated enzymes, transcription factors and adhesion proteins. Novel approaches, including experimental and in silico protein motif search should be adopted to assign functions to these cryptic genes which is likely to fast track drug target search.