cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterization of Active/Passive Pneumatic Actuators for Assistive Devices

Assistive devices have been developed for power augmentation and task-oriented assistance such as loaded walking. The effective joint dynamics of the user can be altered using a wearable system, providing assistance when a task is performed. The authors have investigated an Active/Passive Pneumatic Actuator (AP2A) for an assistive device, which has a simple structure and responds as a passive nonlinear spring with controllable stiffness. This paper introduces a novel controller for the AP2 $A$ and validates the performance through experiments. The developed controller is found to stabilize at the desired stiffness response within 1 second, confirming the ability of the AP2 $A$ to act as an adjustable passive nonlinear spring.
Relational Similarity Machines (RSM): A Similarity-based Learning Framework for Graphs

Relational machine learning has become increasingly important due to the recent proliferation and ubiquity of network data. However, existing methods are not designed for interactive learning and have many unrealistic assumptions that greatly limit their utility in practice. For instance, most existing work has focused on graphs with high relational autocorrelation (homophily) and perform poorly otherwise. To overcome these limitations, this paper presents a similarity-based relational learning framework called Relational Similarity Machines (RSM) for networks with arbitrary relational autocorrelation. The RSM framework is designed to be fast, accurate, and flexible for learning on a wide variety of networks. The experiments demonstrate the effectiveness of the RSM framework.
Not the comfy chair! Cancer drugs that act against multiple active sites

Introduction: Discoveries of novel signal transduction pathways in the 1990s stimulated drug companies to develop small molecule tyrosine kinase and serine / threonine kinase inhibitors which were based on catalytic site inhibition. All kinases bind ATP and catalyze phosphate transfer and, therefore, inhibitors that block ATP binding and its metabolism would be predicted to have a known on-target specificity but were also likely to have many unknown or unrecognized targets due to similarities in all ATP binding pockets. This on-target off-target biology of kinase inhibitors, which exhibit a "signal" in the clinic, means that therapeutically valuable agents are acting through unknown biological processes to mediate their anti-tumor effects.Areas covered: This perspective discusses drug therapies whose actions cannot be explained by their actions on the original targeted kinase; it concludes with a methodology to screen for changes in cell signaling via in-cell western immunoblotting.Expert opinion: Most malignancies do not depend on survival signaling from one specific mutated proto-oncogene, especially for previously treated malignancies where multiple clonal variants of the primary tumor have evolved. Hence, the concept of a highly "personalized medicine" approach fails because it is unlikely that a specific therapy will kill all clonal variants of the tumor.
“No Man Can Be the Judge of His Own Cause”: Applying the Principles of Due Process to Our Elections

The chief election official of a state has broad authority to decide who gets to vote based on policies that regulate voter registration applications, absentee ballots, and state voter rolls. They ...
Countries and Cultural Differences in the Stigma of Mental Illness: The East–West Divide:

Mental illness is a global public health crisis. Although rates of untreated cases stand as a primary problem, stigma is a significant obstacle. Yet, global differences in levels and roots of stigm...
Building flat-band lattice models from Gram matrices

We propose a powerful and convenient method to systematically design flat-band lattice models, which overcomes the difficulties underlying the previous method. Especially, our method requires no elaborate calculations, applies to arbitrary spatial dimensions, and guarantees to result in a completely flat ground band. We use this method to generate several classes of lattice models, including models with both short- and long-range hoppings, both topologically trivial and nontrivial flat bands. Some of these models were previously known. Our method, however, provides important insight. For example, we have reproduced and generalized the Kapit-Mueller model [Kapit and Mueller, Phys. Rev. Lett. 105, 215303 (2010)] and demonstrated a universal scaling rule between the flat-band degeneracy and the magnetic flux that was not noticed in previous studies. We show that the flat band of this model results from the (over-)completeness properties of coherent states.
Time to accept a new old standard of care in cervical cancer.

The Laparoscopic Approach to Cervical Cancer (LACC) trial disrupted the long-standing consensus that minimally invasive and open surgery are equally effective approaches to radical hysterectomy for cervical cancer.[1][1] The study’s main finding, namely that radical hysterectomy by a minimally
Discrete multi-load truss sizing optimization: model analysis and computational experiments

Discrete multi-load truss sizing optimization (MTSO) problems are challenging to solve due to their combinatorial, nonlinear, and non-convex nature. This study highlights two important characteristics of the feasible set of MTSO problems considered here, in which force balance equations, Hooke’s law, yield stress, bound constraints on displacements, and local bucking are taken into account. Namely, we use the linear or bilinear nature of the problem to take advantage of re-scaling properties of both the problem’s design and auxiliary variables, as well as to extend the superposition principle to the case in which nonlinear stress constraints are considered. Taking advantage of these characteristics, we extend the neighborhood search mixed-integer linear optimization (NS-MILO) method (Shahabsafa et al. in SMO 63: 21–38, 2018), which provides an effective heuristic solution approach based on exact solution methods for MILO problems. Through extensive computational experiments, we demonstrate that the extended NS-MILO method provides high-quality solutions for large-scale discrete MTSO problems in a reasonable time.
The Kiowa Language and Culture Revitalization Program: Designing a Community-based Learning Model for an Endangered Language

The Kiowa Language and Culture Revitalization Program is a community-based learning model designed to help language learners construct knowledge and practice an endangered language in situ through networks of community members, protocols, scaffolding, and tools. In this model, tribal members act as linguistic and cultural resources, and teachers use specially designed tools to elicit knowledge from tribal elders and to build knowledge of language and culture within the community. The design of the learning model is intended to serve as a framework for a variety of communities responding to the prospect of language extinction.
Platelet aggregation responses are critically regulated in vivo by endogenous nitric oxide but not by endothelial nitric oxide synthase

Background and purpose: Although exogenous nitric oxide (NO) clearly modifies platelet function, the role and the source of endogenous NO in vivo remain undefined. In addition, endothelial NO synthase (NOS-3) critically regulates vessel tone but its role in modulating platelet function is unclear. In this paper we have investigated the roles of endogenous NO and NOS-3 in regulating platelet function in vivo and determined the functional contribution made by platelet-derived NO. Experimental approach: We used a mouse model for directly assessing platelet functional responses in situ in the presence of an intact vascular endothelium with supporting in vitro and molecular studies. Key results: Acute NOS inhibition by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) enhanced platelet aggregatory responses to thrombin and platelets were shown to be regulated primarily by NO sources external to the platelet. Elevation of endogenous NOS inhibitors to mimic effects reported in patients with cardiovascular diseases did not enhance platelet responses. Platelet responsiveness following agonist stimulation was not modified in male or female NOS-3−/− mice but responses in NOS-3−/− mice were enhanced by L-NAME. Conclusions and implications: Platelets are regulated by endogenous NO in vivo, primarily by NO originating from the environment external to the platelet with a negligible or undetectable role of platelet-derived NO. Raised levels of endogenous NOS inhibitors, as reported in a range of diseases were not, in isolation, sufficient to enhance platelet activity and NOS-3 is not essential for normal platelet function in vivo due to the presence of bioactive NO following deletion of NOS-3.
The URA97 Model for Role-Based User-Role Assignment

In role-based access control (RBAC) permissions are associated with roles, and users are made members of appropriate roles thereby acquiring the roles’ permissions. The principal motivation behind RBAC is to simplify administration. An appealing possibility is to use RBAC itself to manage RBAC, to further provide administrative convenience. In this paper we introduce a role-based administrative model, called URA97 (user-role assignment ’97), for assignment of users to roles.
Do firms borrow at the lowest-cost maturity? The long-term share in debt issues and predictable variation in bond returns

We document that firms tend to borrow at the lowest-cost maturity. In aggregate timeseries data, the share of long-term debt issues in total debt issues is negatively related to subsequent excess bond returns, meaning that firms substitute toward long-term debt when the cost of long-term debt is low relative to the cost of short-term debt. The longterm share is also contemporaneously negatively related to the components of the longterm interest rate that predict higher excess bond returns, including inflation, the real short-term rate, and the term spread. The results suggest that firms use predictable variation in excess bond returns in an effort to reduce the cost of capital.
Abstract 18084: MiR-30e Targets IGF2-Regulated Osteogenesis in Bone Marrow Derived Mesenchymal Stem Cells, Aortic Smooth Muscle Cells, and APOE-/- Mice

Objective: In atherosclerosis, activation of an osteogenic transcriptional program in de-differentiated mesenchymal-like smooth muscle cells (SMCs) contributes substantially to the initiation of aortic calcification. We found that aortic miR-30e is downregulated with age and atherosclerosis and inversely proportional to osteogenic markers. To assess the effect of miR-30e downregulation, we tested the hypothesis that miR-30e regulates osteogenic program in bone marrow derived mesenchymal stem cells (MSCs), aortic SMCs, and APOE-/- mice. Method and Results: In aortas of old (13.5 mo) and young (6 mo) wild type and APOE-/- mice (n=4-15), we found that NFYC gene and hosted miR-30e transcripts are downregulated with age and atherosclerosis while the osteogenic markers Runx2, Opn, and Igf2 are upregulated - p Conclusion: MiR-30e represses the osteogenic program in MSCs and SMCs by targeting IGF2 and drives their differentiation into different lineages. Downregulation of miR-30e in aortas with age and atherosclerosis may trigger vascular calcification.
A contraction of the Lucas polygon

The celebrated Gauss-Lucas theorem states that all the roots of the derivative of a complex non-constant polynomial p lie in the convex hull of the roots of p, called the Lucas polygon of p. We improve the Gauss-Lucas theorem by proving that all the nontrivial roots of p' lie in a smaller convex polygon which is obtained by a strict contraction of the Lucas polygon of p.
Security-Aware Resource Allocation for Mobile Cloud Computing Systems

In this paper, a novel resource allocation algorithm is proposed for secure mobile cloud computing systems. The mobile request for using cloud resource is classified according to its level of security requirement and the amount of required resource for remote computing. We formulate the resource allocation problem as a semi-Markov decision process under the average reward criterion, where the average reward of states is expected to be optimized. Through maximizing the long-term reward while meeting the system requirements of the blocking probability and the amount of resource requested with a security guarantee, the optimal resource allocation policy is calculated by using the linear programming. Simulation results demonstrate that the system adaptively modifies the resource allocation policy for cloud computing, and determines whether to utilize extra resource for security implementation according to the mobile request type, the current traffic, and the cloud resource availability.
Relevance of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) in the structural integrity of the chromatoid body during spermatogenesis.

Abstract Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), a multifunctional protein and a component of ribonucleoprotein complexes, is essential for the completion of spermatogenesis. We investigated the nuclear/cytoplasmic shuttling of GRTH in germ cells and its impact on the chromatoid body (CB)—a perinuclear organelle viewed as a storage/processing site of mRNAs. GRTH resides in the nucleus, cytoplasm and CB of round spermatids. Treatment of these cells with inhibitors of nuclear export or RNA synthesis caused nuclear retention of GRTH and its absence in the cytoplasm and CB. The nuclear levels of GRTH bound RNA messages were significantly enhanced and major reduction was observed in the cytoplasm. This indicated GRTH main transport function of mRNAs to the cytoplasm and CB. MVH, a germ cell helicase, and MIWI, a component of the RNA-induced-silencing complex (RISC), confined to the CB/cytoplasm, were absent in the CB and accumulated in the cytoplasm upon treatment. This also occurred in spermatids of GRTH-KO mice. The CB changed from lobular-filamentous to a small condensed structure after treatment resembling the CB of GRTH-KO. No interaction of GRTH with MVH or RISC members in both protein and RNA were observed. Besides of participating in the transport of messages of relevant spermatogenic genes, GRTH was found to transport its own message to cytoplasmic sites. Our studies suggest that GRTH through its export/transport function as a component of mRNP is essential to govern the CB structure in spermatids and to maintain systems that may participate in mRNA storage and their processing during spermatogenesis.
Quantitative Fluorescence Photoacoustic Tomography

Fluorescence photoacoustic tomography (fPAT) is a multimodality biomedical imaging technique that combines high-resolution ultrasound imaging with high-contrast fluorescence optical tomography. In the first step of fPAT, one utilizes the photoacoustic effect to recover the total absorbed energy map inside the media with ultrasound tomography. In the second step, called quantitative fPAT (QfPAT), one uses interior absorbed energy data to recover either the quantum efficiency or the concentration distribution or both of the fluorophores inside the media. The objective of this work is to derive the mathematical model for QfPAT and to study the corresponding inverse problems. We derive some uniqueness and stability results on these inverse problems and propose a few (often explicit) reconstruction algorithms. Numerical simulations based on synthetic data are presented to verify the theory and algorithms proposed.
Miniature radio-frequency mobility analyzer as a gas chromatographic detector for oxygen-containing volatile organic compounds, pheromones and other insect attractants.

Abstract A high electric field, radio-frequency ion mobility spectrometry (RF-IMS) analyzer was used as a small detector in gas chromatographic separations of mixtures of volatile organic compounds including alcohols, aldehydes, esters, ethers, pheromones, and other chemical attractants for insects. The detector was equipped with a 2 mCi 63Ni ion source and the drift region for ion characterization was 5 mm wide, 15 mm long and 0.5 mm high. The rate of scanning for the compensation voltages was 60 V s−1 and permitted four to six scans to be obtained across a capillary chromatographic elution profile for each component. The RF-IMS scans were characteristic of a compound and provided a second dimension of chemical identity to chromatographic retention adding specificity in instances of co-elution. Limits of detection were 1.6–55×10−11 g with an average detection limit for all chemicals of 9.4×10−11 g. Response to mass was linear from 2–50×10−10 g with an average sensitivity of 4 pA ng−1. Separations of pheromones and chemical attractants for insects illustrated the distinct patterns obtained from gas chromatography with RF-IMS scans in real time and suggest an analytical utility of the RF-IMS as a small, advanced detector for on-site gas chromatographs.
Drug Utilization and Prescribing Patterns in a Skilled Nursing Facility: The Need for a Rational Approach to Therapeutics

: A study was made of 50 patients drawn at random from a Skilled Nursing Facility (SNF) attended by seven physicians. For 59 percent of these patients, polypharmacy was practiced but no substantiating diagnoses were recorded. Approximately half of the drugs were administered pro re nata. More drugs were prescribed in potentially toxic dosages than in subtherapeutic dosages. The risk of an adverse drug reaction (ADR) was most often associated with anticholinergic agents, sedative-hypnotic drugs, and neuroleptics (thioridazine and chlorpromazine), particularly when prescribed concurrently. Risk of an ADR was highest when a drug was prescribed without recording a definite diagnostic indication. Lack of consistency by individual physicians in their approaches to the therapy of similar disease entities in comparable patients tended to support the concept of peer review in SNFs and also the need for teaching a rational approach to therapeutics in SNFs based on clinical pharmacology as applied to the elderly.
Lattice spacing variations in gold-nickel superlattices

Strained layered superlattices of Au and Ni have been grown by sputter deposition. The repeat periodicity, d Au/Ni , of the (111) oriented submicron thick films ranged from 0.78 to 4.60 nm. A variation of lattice spacing, d 111 , in the superlattice growth direction, with the repeat periodicity of the superlattice has been measured using standard theta/2theta CuKa x-ray diffraction. A minimum in (1/d 111 ) was found at d Au/Ni equal 2 nm, with increasing values of (1/d 111 ) above and below this repeat period. This variation of (1/d 111 ) with d Au/Ni , reported for the first time for the Au/Ni system, is anticipated in thosenoble/transition metal superlattice systems which exhibit the supermodulus effect“.
Wall coating behavior of catalyst slurries in non-porous ceramic microstructures

Abstract We report the use of the gas-displacement technique to generate wall coatings of catalyst slurries in fused silica capillaries, as well as ceramic microreactors. The non-porous and glassy surfaces make it difficult to prepare adherent coatings within ceramic structures. In the fused silica capillaries, we were able to show adherent catalyst coats up to 20 μ m thick and found that the maximum fraction coated decreased as the capillary diameter decreased. We developed a model for the various diameters showing the relationship of the fraction coated versus the capillary number, Ca. It was determined that the coating behavior was controlled by the coupled effects of the fluid rheology and the dramatic increase in the Reynold's number as the diameters decreased. For the ceramic microreactor, we determined that the coatings were adherent and tests showed the wall-coated catalyst in these structures to be catalytically active for the steam reforming of methanol.
Extending vaterite microviscometry to ex vivo blood vessels by serial calibration

The endothelial glycocalyx layer is a ~2 µm thick glycosaminoglycan rich pericellular matrix expressed on the luminal surface of vascular endothelial cells, which has implications in vessel mechanics and mechanotransduction. Despite its role in vascular physiology, no direct measurement has of yet been made of vessel glycocalyx material properties. Vaterite microviscometry is a laser tweezers based microrheological method, which has been previously utilized to measure the viscosity of linear and complex fluids under flow. This form of microrheology has until now relied on complete recollection of the forward scattered light. Here we present a novel method to extend vaterite microviscometry to relatively thick samples. We validate our method and its assumptions and measure the apparent viscosity as a function of distance from the vascular endothelium. We observe a differential response in conditions designed to preserve the EGL in comparison to those designed to collapse it.
Termination of Protease-activated Receptor-1 Signaling by β-Arrestins Is Independent of Receptor Phosphorylation *

Protease-activated receptor 1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is the prototypic member of a family of protease-activated receptors. PAR1 is irreversibly proteolytically activated; thus, the magnitude and duration of thrombin cellular responses are determined primarily by mechanisms responsible for termination of receptor signaling. Both phosphorylation and beta-arrestins contribute to rapid desensitization of PAR1 signaling. However, the relative contribution of each of these pathways to the termination of PAR1 signaling is not known. Co-expression of PAR1 with beta-arrestin 1 (betaarr1) in COS-7 cells resulted in a marked inhibition of PAR1 signaling, whereas beta-arrestin 2 (betaarr2) was essentially inactive. Strikingly, signaling by a PAR1 cytoplasmic tail mutant defective in agonist-induced phosphorylation was also attenuated more effectively by betaarr1 compared with betaarr2. In contrast, both beta-arrestin isoforms were equally effective at desensitizing the substance P receptor, a classic reversibly activated GPCR. PAR1 coimmunoprecipitated betaarr1 in an agonist-dependent manner, whereas betaarr2 association was virtually undetectable. Remarkably, betaarr1 also interacted with phosphorylation defective PAR1 mutant, whereas betaarr2 did not. Moreover, constitutively active beta-arrestin mutants, betaarr1 R169E and betaarr2 R170E, that bind to activated receptor independent of phosphorylation failed to enhance either wild type or mutant PAR1 desensitization compared with normal versions of these proteins. In contrast, beta-arrestin mutants displayed enhanced activity at desensitizing the serotonin 5-hydroxytryptamine(2A) receptor. Taken together, these results suggest that, in addition to PAR1 cytoplasmic tail phosphorylation itself, beta-arrestin binding independent of phosphorylation promotes desensitization of PAR1 signaling. These findings reveal a new level of complexity in the regulation of protease-activated GPCR signaling.
Rigorous evaluation research among US police departments: special cases or a representative sample?

This study considers whether police departments’ characteristics relate to the methodology and results of the evaluations that they participate in, and contrasts police departments that have carried out rigorous crime prevention research to comparison groups of US police agencies. Findings include departments that participate in quasi-experimental crime prevention research are larger and more likely to find statistically significant successes than those that participate in experiments, and evaluators differ in composition and practices from most US police departments. This suggests that researchers and policy makers should involve smaller suburban and rural police agencies to increase the generalizability of evaluation research.
Solid state structure–property behavior of semicrystalline poly(ether-block-amide) PEBAX® thermoplastic elastomers

Abstract The solid state structure–property behavior was investigated of a series of poly(ether- block -amide) PEBAX ® thermoplastic elastomers based on nylon 12 and poly(tetramethylene oxide) with varying hard segment content. Particular emphasis was placed on better defining the morphological features of this entire series of commercially available materials. Compression molded and solution cast samples were studied by the techniques of DMA, DSC, WAXS, SAXS, AFM, SALS and stress–strain response. The strain-induced crystallization behavior of the soft polyether (PE) segments was also investigated. All samples exhibited a microphase separated morphology over a broad temperature range. As expected, an increase in the interconnectivity of the polyamide hard phase was greatly controlled by the polyamide (PA) content. Due to the crystallization of the PA hard segment, the formation of PA lamellar crystals was noted in both melt and solution cast films. At the higher PA contents, a distinct spherulitic superstructure was also observed but this form of morphological texture was diminished as the PE soft segment content increased. Limited studies of the deformation/recovery behavior of the spherulitic superstructure provided further information concerning the interaction between the hard and soft segments.
A case study of LEGO Mindstorms'™ suitability for artificial intelligence and robotics courses at the college level

This paper examines LEGO Mindstorms'™ suitability as a hardware platform for integrating robotics into an Artificial Intelligence course organized around the agent paradigm popularized by Russell and Norvig. This evaluation discusses how kits and projects based on Mindstorms supported students' exploration of the issues behind the design of agents from three classes in Russell and Norvig's intelligent agent taxonomy. The paper's investigation also examines several popularly-perceived limitations of the Mindstorms package for college-level robotics projects and shows that most of these "limitations" are not serious impediments to Mindstorms' use, while certain other of these "limitations" do indeed present challenges to the platform's use.
The conversion of fibrinogen to fibrin. VII. Rigidity and stress relaxation of fibrin clots; effect of calcium

1. 1. Dynamic rigidity has been measured by the method of wave propagation in bovine fibrin clots at pH 7.0 at various fibrin concentrations and temperatures, and in the absence and presence of small amounts of calcium. Static rigidity and stress relaxation have been measured at pH 6.2 and 7.0 at various temperatures with and without calcium. 2. 2. The dynamic rigidity without calcium decreases reversibly with increasing temperature between 5 ° and 30 °C., and at 25 ° is proportional to the 2.3 power of the fibrin concentration. The addition of small amounts of calcium (in the presence of the serum factor of Laki and Lorand, as deduced from insolubility in 3.5 M urea) increases the rigidity somewhat and diminishes the temperature dependence. 3. 3. In the presence of calcium, the dynamic rigidity (corresponding to measurement within a millisecond) agrees with the static rigidity (corresponding to measurement within several seconds). In the absence of calcium, the static rigidity cannot be determined because of rapid stress relaxation. 4. 4. The rate of relaxation of stress in clots formed without calcium increases rapidly with increasing temperature; when the strain is returned to zero after relaxation, a reverse stress appears which in turn relaxes. 5. 5. The rate of relaxation of stress in clots formed with calcium is extremely small. 6. 6. The results indicate that in clots formed without calcium some of the linkages which compose the network are weak associations which can easily rearrange. In clots formed in the presence of calcium (and serum factor), the network strands are joined by bonds of a far more permanent nature.
Nonstarter Lactobacilli in Cheddar Cheese: A Review

Abstract Lactobacilli constitute the majority of nonstarter lactic acid bacteria (NSLAB) in Cheddar cheese. Species predominating are Lactobacillus casei, Lactobacillus plantarum , and Lactobacillus brevis . Typical cell densities in Cheddar cheese range from 10 to 10 4 /g during the first 10 d to about 10 8 /g within a few weeks postmanufacture. Numbers in cheese are affected by numbers in raw milk and the extent of postpasteurization contamination. Lactobacilli sustain growth in cheese depleted of fermentable carbohydrate by metabolizing peptides, amino acids, sugars released from enzymic hydrolysis of casein, and products of degrading starter bacteria. Lactobacilli, which require several amino acids for growth, possess numerous proteases and peptidases. Peptidases produced by L. casei include dipeptidase, tripeptidase, carboxypeptidase, aminopeptidase, and endopeptidase. Results have been variable in numerous experiments testing the use of selected lactobacilli as adjuncts to lactic starter culture for cheese ripening. Results depended on numbers, strain, type of cheese, and condition of manufacture. Shocking lactobacilli with heat, freezing, lysozyme, ultrasound, organic solvents, or alkaline conditions has been used to minimize proteolytic activity while enhancing peptidolysis. These efforts to accelerate cheese ripening by increasing amounts of active peptidases have been only partially successful.
Mitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor.

Head and neck squamous cell carcinomas (HNSCC) are characterized by upregulation of the epidermal growth factor receptor (EGFR), where EGFR serves as a potential therapeutic target. We previously reported that a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) autocrine growth pathway is activated early in HNSCC carcinogenesis. In the present study, we examined the mechanism of EGFR activation by GRP/GRPR in HNSCC proliferation. In HNSCC cells that express elevated levels of both GRPR and EGFR, we found that GRP induced rapid phosphorylation of EGFR as well as p44/42-MAPK activation. Using several EGFR-specific tyrosine kinase inhibitors and cells derived from EGFR knockout mice, we demonstrated that GRP-induced p44/42-MAPK activation was dependent upon EGFR activation. Further investigation demonstrated that cleavage of transforming growth factor-alpha (TGF-α) by matrix metalloproteinases mediated GRP-induced MAPK activation. In addition, HNSCC proliferation stimulated by GRP was eliminated upon specific inhibition of EGFR or MEK, and GRP failed to stimulate proliferation in EGFR-deficient cells. These results imply that the mitogenic effects of GRP in HNSCC are mediated by extracellular release of TGF-α and require the activation of an EGFR-dependent MEK/MAPK-dependent pathway.
Theoretical Investigations on the Light Scattering of Colloidal Spheres. V. Forward Scattering

The scattering of light, by nonabsorbing colloidal spheres, in the direction of the primary beam (forward direction), is calculated by means of the Mie theory as a function of α and m. The parameters considered are: α=1(1)15 for m=1.05(0.05)1.30 and, in addition, α=0.2(0.2)15.2 for m=1.20. In addition to the i values, the experimentally important quantity, I180/I0c, obtainable by Zimm plots, is evaluated. Its variation with particle size is compared to that of the total turbidity. The performance of the hitherto almost exclusively used Rayleigh‐Gans‐Debye equation is tested quantitatively against the exact Mie data. The advantages of the ``forward scattering method'' for determining particle sizes are enumerated and a series of desirable definitions and clarifications of angular light scattering quantities are included.
Self-Cultivation and Moral Choice

Philosophical luminaries including Aristotle, Immanuel Kant, David Hume, and John Stuart Mill have all theorized that our human capacity of reason calls us to become the best that we can be by developing our “natural abilities.” This article explores the thesis that the development of our talents is not a moral duty to oneself and suggests that it may be avoided for other reasons than failures of rationality. In the face of the opportunity-costs associated with different life-goals, resistance to developing our powers may spring from an informed and perfectly rational choice in favor of an equally valuable alternative to talent development as a way of life. Thus, the arguments in this essay suggest that the predominant, rationalistic view in defense of a duty to develop one’s talents ignores a distinctively human capacity, namely, the capacity for reasoned moral choice. The paper argues, however, that we do well in viewing the development of one’s talents as worthwhile. In other words, it is correct to sustain that the individual would be acting in a morally deficient manner if she declined to develop her abilities for the wrong reasons even if no duty to self to avoid that course of action exists.
Neuroscience: What females really want.

The identification of neural subcircuits used by female fruit flies to make a choice about whether to copulate with a potential mate provides a template for understanding how the brain integrates complex information to reach decisions.
Lobster GABA receptor subunit expressed in neural tissues.

A cDNA encoding an ionotropic gamma-aminobutyric acid (GABA) receptor subunit was isolated from a lobster (Homarus americanus) cDNA library. A longer version of this cDNA, containing a 108-bp insert, was also detected. The two cDNAs are predicted to encode alternatively spliced proteins of 485 and 521 amino acids, respectively. The sequences were most similar to the Drosophila RDL (resistance to dieldrin) GABA subunit with 54% identity, and 30–35% identity with vertebrate ionotropic GABA receptor subunits. Only the shorter clone formed functional ion channels when transfected into human embryonic kidney (HEK) 293 cells. GABA caused a Cl--selective current in the presence of GABA that was blocked by picrotoxin. The GABA-induced current was weakly sensitive to the GABAA antagonist, bicuculline, but was enhanced by pentobarbital. Expression of the GABA receptor mRNA was highest in brain and the olfactory organ, but was not detected in leg muscle. These data suggest that the isolated cDNAs are likely to encode proteins that comprise subunits of native GABA receptors expressed in olfactory receptor neurons and projection neurons of the olfactory deutocerebrum. J. Neurosci. Res. 59:534–541, 2000 © 2000 Wiley-Liss, Inc.
Assay sensitivity and study features in neuropathic pain trials: An ACTTION meta-analysis

Objective: Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials. Methods: We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain. Results: There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regression analyses indicated that larger SESs were significantly associated with trials that had 1) greater minimum baseline pain inclusion criteria, 2) greater mean subject age, 3) a larger percentage of Caucasian subjects, and 4) a smaller total number of subjects. In a multiple meta-regression analysis, the associations between SES and minimum baseline pain inclusion criterion and age remained significant. Conclusions: Our analyses have examined potentially modifiable correlates of study SES and shown that a minimum pain inclusion criterion of 40 or above on a 0 to 100 scale is associated with a larger SES. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of falsely negative outcomes in clinical trials of efficacious treatments for neuropathic pain.
Function of lymphocytes and macrophages after cryopreservation by procedures for pancreatic islets: potential for reducing tissue immunogenicity.

The survival of tissue allografts can be extended by pretreating the tissue to remove the stimulatory leucocytes that populate the graft; with this in mind, we have recently begun to explore a cryobiological approach to modulating tissue immunogenicity by using the differential susceptibility of different cells to freezing injury. The sensitivity of leucocytes to fast cooling rates, which were used in procedures that have been reported to yield viable pancreatic islets of Langerhans, was examined. The loss of both cell numbers and the ability of peripheral blood lymphocytes to undergo blastogenic transformation in response to the mitogen concanavalin A after freezing and thawing was determined over a range of cell concentrations using the “curve-shift” method. Lymphocytes frozen at 1 °C/min by a control procedure that was designed to yield maximum survival of lymphocytes showed that although there was a decrease in the number of responding cells, there was no reduction in the ability of the recovered cells to undergo blastogenesis when compared with the response of nonfrozen cells. However, cooling at 1 °C/min in the experimental procedures resulted in both the loss of cells as well as a marked reduction in the ability of recovered cells to incorporate 125I-deoxyuridine into nucleic acid. Cells cooled at either 20 or 75 °C/min by any of the procedures showed total inability to respond to stimulation. Lysozyme is produced continuously by all types of macrophages in culture. The large net increase in total lysozyme content of macrophage cultures is therefore a useful measure of the viability of these accessory cells. Cooling at 1 °C/min by a control, optimized procedure yielded 91% survival of viable peritoneal exudate cells. Cooling at either 1 or 20 °C/min in the experimental procedures resulted in 72–75% survival of cells frozen by one method and 33% survival when frozen by an alternative procedure. Negligible recovery of viable cells was obtained after cooling at 75 °C/min. The preservation protocols employed in this study differ significantly in the variables known to influence the survival of the cells; these include the concentration of cryoprotectant (CPA), the length and temperature of exposure to CPA, the dilution regimen, and the optimum cooling rate for survival of pancreatic islets. This study therefore defines clearly those conditions most likely to effect a depletion of “passenger” lymphoid cells by freezing during the Cryopreservation of islets of Langerhans.
The bHLH Protein, MUTE, Controls Differentiation of Stomata and the Hydathode Pore in Arabidopsis

Stomata are turgor-driven epidermal valves on the surface of plants that allow for efficient gas and water exchange between the plant and its environment. The Arabidopsis thaliana basic helix-loop-helix (bHLH) protein, MUTE, is a master regulator of stomatal differentiation where it is required for progression through the stomatal lineage and the differentiation of stomata. The genetic control of stomatal spacing across the epidermal surface is variable in different organs. For instance, a distinct suite of genes from those in leaves regulates stomatal patterning in hypocotyls. Here we report that regardless of organ type, MUTE controls downstream events directing stomatal differentiation, specifically the transition from meristemoid to guard mother cell. Ectopic MUTE expression is sufficient to over-ride cell fate specification in cell types that do not normally differentiate stomata. Furthermore, MUTE is required for the production of the structure evolutionarily related to stomata, the hydathode pore. Consistently, MUTE displays expression at the tip of cotyledons and leaves, thus co-localizing with the auxin maxima. However, MUTE itself was not regulated by the auxin, and the absence of hydathode pores in mute did not affect the auxin maxima. Surprisingly, our analysis revealed that the requirement for MUTE could be partially circumvented under conditions of compromised inhibitory signaling.
Spectroscopy and reactivity of a photogenerated tryptophan radical in a structurally defined protein environment.

Near-UV irradiation of structurally characterized [Re(I)(CO)_3(1,10-phenanthroline)(Q107H)](W48F/Y72F/H83Q/Y108W)AzM(II) [Az = Pseudomonas aeruginosa azurin, M = Cu, Zn]/[Co(NH_3)_5Cl]Cl_2 produces a tryptophan radical (W108•) with unprecedented kinetic stability. After rapid formation (k = 2.8 × 10^6 s^(-1)), the radical persists for more than 5 h at room temperature in the folded ReAzM(II) structure. The absorption spectrum of ReAz(W108•)M(II) exhibits maxima at 512 and 536 nm. Oxidation of K_4[Mo(CN)_8] by ReAz(W108•)Zn(II) places the W108•/W108 reduction potential in the protein above 0.8 V vs NHE.
Posterior Reversible Encephalopathy Syndrome and Eclampsia: Pressing the Case for More Aggressive Blood Pressure Control

OBJECTIVE To assess the prevalence, clinical presentations, and neuroimaging abnormalities in a series of patients treated for eclampsia at Mayo Clinic in Rochester, MN. PATIENTS AND METHODS We reviewed the records of all pregnant patients diagnosed as having eclampsia at Mayo Clinic in Rochester, MN, between January 1, 2001, and December 31, 2008. All patients who underwent neuroimaging were identified, and all studies were reviewed by an independent neuroradiologist. Comparisons were made between groups who did and did not undergo imaging to identify differentiating clinical or laboratory variables. RESULTS Thirteen cases of eclampsia were found, with neuroimaging studies available for 7: magnetic resonance imaging (n=6) and computed tomography (n=1). All 7 patients developed eclamptic seizures, and 2 of 7 patients had severe hypertension, with recorded systolic blood pressures exceeding 180 mm Hg. Neuroimaging showed characteristic changes of posterior reversible encephalopathy syndrome (PRES) in all patients. Follow-up imaging showed resolution in 2 of 3 patients; 1 patient had residual neuroimaging abnormalities. CONCLUSION Our results suggest that the clinical syndrome of eclampsia is associated with an anatomical substrate that is recognizable by neuroimaging as PRES. The levels of blood pressure elevation are lower than those reported in cases of PRES because of hypertensive encephalopathy. Further studies are needed to determine whether more aggressive blood pressure control and early neuroimaging may have a role in the management of these patients.
Critically ischemic myocardium in clinically stable patients following thrombolytic therapy for acute myocardial infarction: Potential implications for early coronary angioplasty in selected patients

Abstract The utility of post-thombolysis, rest-redistribution thallium (TI)-201 scintigraphy was studied in 32 patients with a first myocardial infarction who were clinically stable following reperfusion. Day 1 scintigraphy obtained 5 ± 4 hours (range 1 to 16) after thrombolysis revealed an average perfusion defect of 6.5 ± 2.6 segments (range 1 to 11). There was a total of 208 abnormal segments, 137 of which were nonreversible at 4 hours, 50 of which were fully or partially reversible, and 21 of which had a reverse redistribution pattern. Repeat TI-201 scintigraphy on day 10 revealed significantly smaller perfusion defects of 4.9 ± 2.4 segments (range 0 to 9) with improvement predominantly of the day 1 reversible segments, and the improvement in segmental perfusion correlated with better regional left ventricular function. Twenty-nine (58%) of the 50 reversible segments normalized by day 10, and 11 (22%) improved, whereas only 16 (12%) of 137 nonreversible segments had normalized by day 10, only 9 had (6%) improved and 112 (82%) were unchanged ( p p p
Conducting research with racial/ethnic minorities: methodological lessons from the NIDA Clinical Trials Network.

Background: Multiple studies in the National Institute on Drug Abuse Clinical Trials Network (CTN) demonstrate strategies for conducting effective substance abuse treatment research with racial/ethnic minorities (REMs). Objectives: The objectives of this article are to describe lessons learned within the CTN to (1) enhance recruitment, retention, and other outcomes; (2) assess measurement equivalence; and (3) use data analytic plans that yield more information. Method: This article includes background information and examples from multiple CTN studies on inclusion, measurement, and data analysis. Results and Conclusions: Seven recommendations are included for conducting more effective research on REMs.
Effects of methyl bromide on antibiotic production by Armillaria mellea

Two isolates of Armillaria mellea (Vahl ex Fr.) Kummer produced in vitro , substances inhibitory to strains of Streptococcus sp., Mucor sp., Trichoderma longibrachiatum , Rifai aggr., T. harzianum , Rifai aggr., Rhizopus stolonifer (Ehrenb. ex Fr.) Lind, Fusarium solani (Mart.) Sacc, F. roseum , Link ex Fr. and to one of two strains of Gliocladium virens , Miller, Giddens & Foster. Antibiotic production was reduced by fumigation of inoculae of A. mellea with sublethal concentrations of methyl bromide. It is suggested that in these conditions, A. mellea is predisposed to subsequent parasitic attack associated with the biological control of A. mellea often reported after fumigation.
Group B streptococcal septicemia following intracavernous injection therapy for erectile dysfunction in diabetes

Autoinjection of vasoactive medicines remains a popular form of treatment for patients with erectile dysfunction. However, it is not without complications. Its use is especially prominent in men with diabetes, since only 50% respond to sildenafil citrate.1 We report life threatening streptococcal septicemia due to intracavernous injection in a man with diabetes requiring surgical corporotomy. CASE REPORT A 40-year-old man with diabetes presented with a 3-day history of fever and penile edema following intracavernous injection of 10 g alprostadil. The patient recalled normal detumescence after intercourse but noticed asymmetrical swelling at the base of the penis, which prompted a visit to the emergency department. Examination revealed a temperature of 100.4F and an uncircumcised penis with retractable foreskin despite mild generalized edema and erythema. The left corporeal body was indurated and tender. White blood cell count was 17,700 and urinalysis was normal. Plasma glucose was 663 mg/dl. The patient was hospitalized for intravenous antibiotics, glucose control and observation. Computerized tomography of the pelvis showed an area of hypoattenuation at the base of the left corporeal body (fig. 1). Retrograde urethrogram was normal. Reexamination of the patient 7 hours later demonstrated increased penile pain, tachycardia, fever of 103F and worsening generalized penile swelling and erythema. The foreskin was now phimotic. Surgical exploration with the patient under anesthesia was performed. The penis was degloved to Buck’s fascia through a circumcision incision, and aspiration of the left corporeal body revealed frank pus. A 1 cm corporotomy was made followed by irrigation and placement of an intracorporeal Penrose drain (fig. 2). A circumcision was then completed with 6 interrupted 3-zero polyglactin sutures placed circumferentially. The patient became afebrile, with normalization of serum glucose and white blood cell count. Intraoperative cultures as well as blood cultures showed group B streptococcus and he remained on appropriate antibiotics for 7 days. He was discharged home on postoperative day 2 following removal of the Penrose drain and Foley catheter. Genital examination appeared normal 4 weeks later. DISCUSSION