cssi/SciSciGPT-SciSciNet huggingface dataset:
19 An Introduction to the Finite-Element Method

This chapter provides a concise review of basic field equations in solid mechanics and then illustrates how the finite-element method (FEM) can be employed to solve them. To motivate the use of the FEM, the author derives the classical equations of mechanical equilibrium. The central feature of the FEM is to reduce the field equations in a physically sound and systematic manner to an assembly of discrete subdomains, or “elements.” The fundamental mechanism that produces forces in elastic deformation is the stretching of atomic bonds. The chapter presents the classical theory of isotropic elastic material responses for three-dimensional states of stress and strain. It discusses relationships between the stress and strain, so-called material laws or constitutive relations for geometrically linear problems (infinitesimal deformations). The chapter describes Hilbertian Sobolev spaces and global/local transformations, and outlines differential properties of shape functions. Keywords: elastic deformation; finite-element method (FEM); Hilbertian Sobolev spaces; infinitesimal linearly elastic constitutive laws; mechanical equilibrium
Evolving Concepts of Self-Determination and Autonomy in International Law: The Legal Status of Tibet

This article traces the evolution of the concept of self-determination from the end of World War I, through the era of decolonization, to the present day when it has become embedded in the human rights framework and, in limited circumstances, is used to justify secession. Various national and international cases are examined in analyzing the jurisprudence of self-determination, as well as the new European standards for State recognition after secession. The concept of autonomy is also examined as possibly providing a solution for disaffected minority groups within a greater territorial unit. The article then applies the self-determination and autonomy frameworks to Tibet and examines possible solutions for assessing Tibet's international status.
Studies Directed Toward the Regioselective Carboxylation of the 4-Oxo-4,5,6,7-Tetrahydrothieno-[3,2-C]pyridine Ring System

Abstract Carboxylation of 4-oxo-4,5,6,7-tetrahydro[3,2-c]pyridine was achieved using a metallation/carbonylation strategy with desired regioselectivity provided by the existing oxo directing group.
Mechanistic Aspects of Metal Sulfate Decomposition Processes

The decomposition reactions of the crystalline sulfate phases CaSO4MgSO4ZnSO4ZnO • 2ZnSO4CuSO4and CuO • CuSO4 were studied by the torsion-effusion method with simultaneous mass-loss measurement, and by mass spectrometry. Decomposition pressures and vapor compositions were derived from the results. In all instances, these phases decompose to the corresponding oxides or oxysulfates, plus a gas phase that would be predominantly SO2 and O2 at equilibrium. However, most of the processes are severely limited kinetically because of failure to attain S03—SO2 equilibrium in the gas phase, and direct desorption of SO3 is frequently observed. Certain noble metals and p-type semiconducting oxides are observed to catalyze the SO3—SO2 conversion and in some instances lead to dramatic increases in the observed effusion pressure. In a few cases, the catalytic additives convert the gas phase to the equilibrium SO2 + O2 composition, but have no detectable effect on decomposition pressure, suggesting that the SO3 to SO2 conversion may or may not be closely coupled to the initial sulfate ion decomposition step. An attempt is made to correlate this wide range of observed behavior. In addition, decomposition pressures derived by extrapolation to zero orifice size are compared with values calculated from thermochemical data to test the suitability of the effusion method for thermodynamic studies of these materials.
bioRxiv: the preprint server for biology

Abstract The traditional publication process delays dissemination of new research, often by months, sometimes by years. Preprint servers decouple dissemination of research papers from their evaluation and certification by journals, allowing researchers to share work immediately, receive feedback from a much larger audience, and provide evidence of productivity long before formal publication. Launched in 2013 as a non-profit community service, the bioRxiv server has brought preprint practice to the life sciences and recently posted its 64,000th manuscript. The server now receives more than four million views per month and hosts papers spanning all areas of biology. Initially dominated by evolutionary biology, genetics/genomics and computational biology, bioRxiv has been increasingly populated by papers in neuroscience, cell and developmental biology, and many other fields. Changes in journal and funder policies that encourage preprint posting have helped drive adoption, as has the development of bioRxiv technologies that allow authors to transfer papers easily between the server and journals. A bioRxiv user survey found that 42% of authors post their preprints prior to journal submission whereas 37% post concurrently with journal submission. Authors are motivated by a desire to share work early; they value the feedback they receive, and very rarely experience any negative consequences of preprint posting. Rapid dissemination via bioRxiv is also encouraging new initiatives that experiment with the peer review process and the development of novel approaches to literature filtering and assessment.
The importomer is a peroxisomal membrane protein translocase

Three sites of membrane protein biogenesis (the endoplasmic reticulum, mitochondria and chloroplasts) receive unfolded substrates from organelle-specific protein targeting factors, then integrate them using separate translocation channels. Peroxisomes also receive membrane proteins from known targeting factors, but whether a separate translocase is needed for integration remains unknown. Here, using a novel genetic screening strategy, we reveal that the importomer--known for matrix protein import--integrates the peroxisomal membrane protein Pex14. In importomer mutants, Pex14 is arrested in a pre-integrated state on the peroxisome surface. To undergo integration, a Pex14 translocation signal binds the importomer9s substrate receptor Pex5 at a distinct site from matrix proteins. En bloc translocation of an engineered protein complex with Pex149s luminal region argues that integration occurs without substrate unfolding. Our work shows that the handling of membrane protein targeting and integration by discrete machineries is a fundamental principle shared by diverse membrane protein biogenesis pathways.
Integrating Viewpoint and Space: How Lamination across Gesture, Body Movement, Language, and Material Resources Shapes Learning

Gesture is recognized as part of and integral to cognition. The value of gesture for learning is contingent on how it gathers meaning against the ground of other relevant resources in the setting—i...
Where Have You Been? Realizing Absorptive Capacity to Leverage Director International Experience

Our paper expands upon extant corporate governance literature to explore the relationship between directors with professional international experience and firm performance. We draw on theory regard...
The effect of tumor grade heterogeneity on recurrence in non-muscle invasive bladder cancer.

Abstract Objective To investigate the outcomes of mixed-grade non-muscle invasive bladder cancer (NMIBC) based on the degree of high-grade predominance. Methods We identified patients in our institutional database who had a transurethral resection of bladder tumor(s) for NMIBC. Tumors with mixed-grade features on pathology report were reanalyzed, assigned the percentage high-grade component, and stratified into ≤ 5% high-grade and > 5% high-grade groups. All others were classified as low-grade or high-grade NMIBC. Differences in recurrence-free survival were assessed by log-rank test. A multivariable Cox regression model was used to evaluate the impact of tumor grade on recurrence, controlling for tumor stage, size, multifocality, and intravesical therapy. Results Two hundred and twenty patients were followed for a median of 2 years; 127 (58%) had low-grade NMIBC, 66 (30%) had high-grade NMIBC, and 27 (12%) had mixed-grade NMIBC. Of the mixed-grade patients, 14 had a ≤ 5% high-grade component, and 13 had a > 5% high-grade component. Recurrence rates across all groups ranged from 42% to 79%. There was no significant difference in intravesical recurrence-free survival among the grade categories as assessed by log-rank test. On multivariable Cox regression analysis, grade category was not significantly associated with likelihood of recurrence. Conclusions The prognosis of mixed-grade histology in NMIBC has not previously been well defined. Although grade category was not found to be an independent significant predictor of recurrence, the recurrence rate for mixed-grade tumors was quite high overall. Further studies are required to better understand appropriate risk stratification and treatment of mixed-grade NMIBC.
Case-control study evaluating risk factors for SARS-CoV-2 outbreak amongst healthcare personnel at a tertiary care center.

Abstract Background Despite several outbreaks of SARS-CoV-2 amongst healthcare personnel (HCP) exposed to COVID-19 patients globally, risk factors for transmission remain poorly understood. Methods We conducted an outbreak investigation and case-control study to evaluate SARS-CoV-2 transmission risk in an outbreak among HCP at an academic medical center in California that was confirmed by whole genome sequencing. Results A total of 7/9 cases and 93/182 controls completed a voluntary survey about risk factors. Compared to controls, cases reported significantly more patient contact time. Cases were also significantly more likely to have performed airway procedures on the index patient, particularly placing the patient on high flow nasal cannula, continuous positive airway pressure (CPAP), or bilevel positive airway pressure (BiPAP) (OR = 11.6; 95% CI = 1.7 –132.1). Discussion This study highlights the risk of nosocomial infection of SARS-CoV-2 from patients who become infectious midway into their hospitalization. Our findings also reinforce the importance of patient contact time and aerosol-generating procedures as key risk factors for HCP infection with SARS-CoV-2. Conclusions Re-testing patients for SARS-CoV-2 after admission in suspicious cases and using N95 masks for all aerosol-generating procedures regardless of initial patient SARS-CoV-2 test results can help reduce the risk of SARS-COV-2 transmission to HCP.
The utilization of perfused cadaver simulation in urologic training: a pilot study.

Background We sought to determine if participating in a surgical training session using perfused fresh human cadavers (PFHC) had a positive effect on urology residents' confidence in performing open and endoscopic procedures. Methods Urology residents at our institution participated in a surgical training session in the West Virginia University Fresh Tissue Training Program, which utilized fresh cadavers with vascular perfusion. The session consisted of performing different urologic procedures (open and endoscopic) on the perfused fresh human cadavers (PFHC). Residents were given a survey to rate their confidence in different urologic procedures before, after, and 6 months after the session. Each procedure on the survey had 3-6 questions associated with it, with scores ranging from 0 (no confidence) to 4 (great confidence). Scores for each procedure before and after the session were compared. Results Six residents participated in the session. There was an increase in the score for every procedure performed after the session. Scores at 6 month follow up remained higher than the pre-session scores. Conclusion PFHCs offer an excellent opportunity to teach a wide variety of urologic procedures to residents. Incorporation of PFHCs may be very useful in urologic training, and further studies on its use are warranted.
Assessing the suitability of mangrove habitats for juvenile Atlantic goliath grouper

While juvenile Atlantic goliath grouper, Epinephelus itajara (Lichtenstein, 1822), are known to depend on mangrove root structure, relationships with water properties (e.g., salinity) and depth remain unclear or understudied. Because availability of suitable mangrove habitat has been suggested as the primary bottleneck to the recovery of this threatened species in the US, we investigated habitat associations of juvenile Atlantic goliath grouper with respect to physical water properties within mangrove habitats. Our study was conducted in six coastal rivers and three canals within the Ten Thousand Islands region of southwest Florida. Results suggested that juvenile Atlantic goliath grouper differed in how they associated with specific mangrove habitats based on season and size. We found that smaller juveniles ( 3 mg L−1) within mangrove habitat. For small juveniles, extreme temperatures influenced habitat association; for large juveniles, extreme salinity influenced distribution. We also found evidence that juvenile Atlantic goliath grouper associated more with natural rivers over man-made canals. The present study has utility for delineating suitable mangrove habitats for protection and potentially in the design of sampling surveys that aim to estimate population abundance.
Model Checking: Theory into Practice

Model checking is an automatic method for verifying correctness of reactive programs. Originally proposed as part of the dissertation work of the author, model checking is based on efficient algorithms searching for the presence or absence of temporal patterns. In fact, model checking rests on a theoretical foundation of basic principles from modal logic, lattice theory, as well as automata theory that permits program reasoning to be completely automated in principle and highly automated in practice. Because of this automation, the practice of model checking is nowadays well-developed, and the range of successful applications is growing. Model checking is used by most major hardware manufacturers to verify microprocessor circuits, while there have been promising advances in its use in software verification as well. The key obstacle to applicability of model checking is, of course, the state explosion problem. This paper discusses part of our ongoing research program to limit state explosion. The relation of theory to practice is also discussed.
Statistical and Neural Network Forecasts of Apparel Sales

In this paper, we are investigating both statistical and soft computing (e.g., neural networks) forecasting approaches. Using sales data from 1997 – 1999 to train our model, we forecasted sales for the year 2000. We found an average correlation of 90% between forecast and actual sales using statistical time series analysis, but only 70% correlation for the model based on neural networks. We are now working to convert standard input parameters into fuzzified inputs. We believe that fuzzy rules would help neural networks learn more efficiently and provide better forecasts.
The Researcher’s Personal Pursuit of Balance Between Academic and Practical Contributions

While reflecting on her own experience with giving back in Zimbabwe, Fortmann considers how the idea of “giving back” sits at the intersection of feminist theory, participatory research, and the democratization of science. From feminist theory arises the question of how to reciprocate to those who have contributed to our research. The participatory research and democratization of science literature push us to recognize and consider the collaborative nature of our research. Fortmann concludes by identifying three categories of reciprocity in research: material, intellectual, and personal. Sharing must occur, regardless of the kind of research taking place.
Learning to Align Sequences: A Maximum-Margin Approach

We propose a discriminative method for learning the parameters of linear sequence alignment models from training examples. Compared to conventional generative approaches, the discriminative method is straightforward to use when operations (e.g. substitutions, deletions, insertions) and sequence elements are described by vectors of attributes. This admits learning flexible and more complex alignment models. While the resulting training problem leads to an optimization problem with an exponential number of constraints, we present a simple algorithm that finds an arbitrarily close approximation after considering only a subset of the constraints that is linear in the number of training examples and polynomial in the length of the sequences. We also evaluate empirically that the method effectively learns good parameter values while being computationally feasible.
Market frictions and stock return dynamics: Evidence from the Athens Stock Exchange

Purpose – This paper seeks to test the hypothesis that stock returns in the Athens Stock Exchange (ASE) adjust asymmetrically to past information due to differential adjustment costs.Design/methodology/approach – The methodological approach is based on the asymmetric price adjustment model suggested by Koutmos. The model is estimated using daily sector stock return data for the ASE over the period 2 January 1992‐1 March 1999.Findings – The empirical evidence suggests that prices respond asymmetrically to past information. Specifically, positive past returns are more persistent than negative past returns of an equal magnitude. This behavior is consistent with an asymmetric partial adjustment price model where news suggesting overpricing (negative returns) are incorporated faster into current market prices than news suggesting underpricing (positive returns).Research limitations/implications – This paper does not investigate the possibility that the asymmetric price adjustment is related to conditional hete...
Human catecholamine sulfotransferase (SULT1A3) pharmacogenetics: functional genetic polymorphism.

Sulfotransferase (SULT) 1A3 catalyzes the sulfate conjugation of catecholamines and structurally related drugs. As a step toward studies of the possible contribution of inherited variation in SULT1A3 to the pathophysiology of human disease and/or variation in response to drugs related to catecholamines, we have resequenced all seven coding exons, three upstream non-coding exons, exon–intron splice junctions and the 5′-flanking region of SULT1A3 using DNA samples from 60 African-American (AA) and 60 Caucasian-American (CA) subjects. Eight single nucleotide polymorphisms (SNPs) were observed in AA and five in CA subjects, including one non-synonymous cSNP (Lys234Asn) that was observed only in AA subjects with an allele frequency of 4.2%. This change in amino acid sequence resulted in only 28 ± 4.5% (mean ± SEM) of the enzyme activity of the wild-type (WT) sequence after transient expression in COS-1 cells, with a parallel decrease (54 ± 2.2% of WT) in level of SULT1A3 immunoreactive protein. Substrate kinetic studies failed to show significant differences in apparent Km values of the two allozymes for either dopamine (10.5 versus 10.2 µm for WT and variant, respectively) or the cosubstrate 3′-phosphoadenosine 5′-phosphosulfate (0.114 versus 0.122 µm, respectively). The decrease in level of immunoreactive protein in response to this single change in amino acid sequence was due, at least in part, to accelerated SULT1A3 degradation through a proteasome-mediated process. These observations raise the possibility of ethnic-specific inherited alterations in catecholamine sulfation in humans.
MSR-MT: The Microsoft Research Machine Translation System

MSR-MT is an advanced research MT prototype that combines rulebased and statistical techniques with example-based transfer. This hybrid, large-scale system is capable of learning all its knowledge of lexical and phrasal translations directly from data. MSR-MT has undergone rigorous evaluation showing that, trained on a corpus of technical data similar to the test corpus, its output surpasses the quality of best-of-breed commercial MT systems.
Decolonizing music education: Moving beyond tokenism

Current music education curricula across Canada designate Western classical music as the music most worthy of study through emphasis on elements of music that are decidedly Western. Despite the way the curriculum is constructed, many music teachers strive to create diverse programs for their students. In her examination of women’s studies programs, Chandra Talpade Mohanty (2003) puts forward three curricular models that describe the manner in which “Other” subject material is engaged in the curriculum within the discipline of women’s studies. I rethink her pedagogical models and apply them to music education. Mohanty’s first two models are more tokenistic in nature while the third model is comparative. While there are benefits to the first two models, the third, when applied to music, reveals that musics are better understood relationally. Mohanty’s (2003) third pedagogical model has much to offer music education.
The latissimus dorsi flap for reconstruction of the brachium and shoulder.

The latissimus dorsi was transferred on its neurovascular pedicle to reconstruct the shoulder or brachium in nineteen patients. Group I consisted of seven patients in whom transfer of the latissimus dorsi was used only to obtain active flexion of the elbow. Although there was complete necrosis of the transferred muscle in one patient, six patients achieved an average of 111 degrees of active flexion and full extension of the elbow. There was only a modest gain in active supination because of pre-existing pronation contractures. The three patients in Group II had sustained loss of the flexor muscles of the elbow and the overlying soft tissue as a result of trauma. After the latissimus dorsi musculocutaneous flexorplasty, an average of 135 degrees of active flexion of the elbow was restored, but there was an average loss of 12 degrees of extension. The three patients in Group III had a large, noninfected defect of the soft tissue over the shoulder or brachium; the bone, shoulder joint, or neurovascular structures were exposed in each patient. Transfer of the latissimus dorsi with the overlying skin provided satisfactory coverage of the defect. The six patients in Group IV had chronic osteomyelitis or septic arthritis of the glenohumeral joint. Treatment consisted of radical debridement of the infected soft tissue and bone followed by transfer of the latissimus dorsi. This provided satisfactory coverage for subsequent osteosynthesis of the humerus or arthrodesis of the shoulder when one of these procedures was indicated. At the time of writing, an average of 2.3 years after the latissimus dorsi transfer, none of the patients in this group (including one who died nine months post-operatively of unrelated causes) had drainage.
Strategy in motion: Using motion pictures to illustrate strategic management concepts

Abstract A company is more likely to enjoy excellent organizational performance if its employees understand the importance of strategic management and are actively engaged in helping the company pursue its strategies. Many employees view strategy as disconnected from their jobs, however, and getting them to embrace strategy can be challenging. Using a series of vivid examples, we describe how motion pictures can bring strategic management concepts to life for employees. By making strategic management concepts more relevant and less abstract, movies can lead employees to enjoy thinking about and discussing strategy.
Management guidelines for efficient irrigation of vegetables using closed-end level furrows

Closed-end level furrows are commonly used to irrigate vegetables in the Lower Colorado River region (LCRR). The application efficiency of furrow irrigation in this area is often low. The objective of this study is to develop management tools and guidelines for the efficient irrigation of vegetables using closed-end level furrows. The study consisted of field experiment and modeling (model calibration, model verification, and the development of management tools by simulation). Field experiments were performed over a period of 27 months. Infiltration parameters were estimated for four soil textural groups (i.e., moderately coarse textured, medium textured, moderately fine textured, and fine textured soils) using a two-point method modified for closed-end level furrows. Model verification shows that the surface irrigation hydraulic model used in this study (SRFR) is capable of simulating the furrow irrigation process with acceptable levels of accuracy. Results of the study also indicate that adequate and efficient irrigations can be achieved using closed-end level furrows through the proper selection of unit inlet flow rate, Qo, and cutoff time, tco. However, given the soil and crop combinations in the LCRR, sometimes significant increases in irrigation efficiency, compared to present levels, can be attained only if furrow lengths are shorter than the typical size currently in use in the LCRR. Limitations of the proposed management tools and on-going research to address these limitations are briefly discussed.
Plasmon resonant liposomes for controlled drug delivery

Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil ® and Ambisome ® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37 o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5 o C increase in temperature or by laser illumination (760 nm and 88 mW/cm 2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.
Drug screening strategy for human membrane proteins: From NMR protein backbone structure to in silica- and NMR-screened hits

About 8000 genes encode membrane proteins in the human genome. The information about their druggability will be very useful to facilitate drug discovery and development. The main problem, however, consists of limited structural and functional information about these proteins because they are difficult to produce biochemically and to study. In this paper we describe the strategy that combines Cell-free protein expression, NMR spectroscopy, and molecular DYnamics simulation (CNDY) techniques. Results of a pilot CNDY experiment provide us with a guiding light towards expedited identification of the hit compounds against a new uncharacterized membrane protein as a potentially druggable target. These hits can then be further characterized and optimized to develop the initial lead compound quicker. We illustrate such "omics" approach for drug discovery with the CNDY strategy applied to two example proteins: hypoxia-induced genes HIGD1A and HIGD1B.
Impact of ENSO on the Atmospheric Variability over the North Atlantic in Late Winter—Role of Transient Eddies

AbstractThe dynamical mechanism for the late-winter teleconnection between El Nino–Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO) is examined using the output from a 2000-yr integration of a coupled general circulation model (GCM). The coupled model captures many salient features of the observed behavior of both ENSO and NAO, as well as their impact on the surface climate in late winter. Both the observational and model data indicate more occurrences of negative phase of NAO in late winter during El Nino events, and positive NAO in La Nina episodes.The potential role of high-frequency transient eddies in the above teleconnection is diagnosed. During El Nino winters, the intensified transient disturbances along the equatorward-shifted North Pacific storm track extend their influences farther downstream. The eddy-induced negative height tendencies are found to be more coherent and stronger over North Atlantic than that over North Pacific. These negative height tendencies over the North...
Functional characterization of α-adrenoceptors mediating pupillary dilation in rats

Previously, we reported that the alpha(1A)-adrenoceptor, but not the alpha(1D)-adrenoceptor, mediates pupillary dilation elicited by sympathetic nerve stimulation in rats. This study was undertaken to further characterize the alpha-adrenoceptor subtypes mediating pupillary dilation in response to both neural and agonist activation. Pupillary dilator response curves were generated by intravenous injection of norepinephrine in pentobarbital-anesthetized rats. Involvement of alpha(1)-adrenoceptors was established as mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenoceptor antagonists, phentolamine (0.3-3 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as by the selective alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg). The alpha(2)-adrenoceptor antagonist, rauwolscine (0.5 mg/kg), was without antagonistic effects. alpha(1A)-Adrenoceptor selective antagonists, 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101; 0.1-1 mg/kg) and 5-methylurapidil (0.1-1 mg/kg), the alpha(1B)-adrenoceptor selective antagonist, 4-amino-2-[4-[1-(benzyloxycarbonyl)-2(S)- [[(1,1-dimethylethyl)amino]carbonyl]-piperazinyl]-6,7-dimethoxyquinazoline (L-765314; 0.3-1 mg/kg), as well as the alpha(1D)-adrenoceptor selective antagonist, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY-7378; 1 mg/kg), were used to delineate the adrenoceptor subtypes involved. Mydriatic responses to norepinephrine were significantly antagonized by intravenous administration of both WB-4101 and 5-methylurapidil, but neither by L-765314 nor by BMY-7378. L-765314 (0.3-3 mg/kg, i.v.) was also ineffective in inhibiting the mydriasis evoked by cervical sympathetic nerve stimulation. These results suggest that alpha(1B)-adrenoceptors do not mediate sympathetic mydriasis in rats, and that the alpha(1A)-adrenoceptor is the exclusive subtype mediating mydriatic responses in this species.
Primary Central Nervous System Phaeohyphomycosis: A Review of 101 Cases

Phaeohyphomycosis refers to infections caused by darkly pigmented fungi. These fungi rarely cause life-threatening disease. We reviewed 101 cases of culture-proven primary central nervous system phaeohyphomycosis reported in the English-language literature from 1966 to 2002. The most frequently isolated species was Cladophialophora bantiana. The next most frequent isolate was Ramichloridium mackenziei, seen exclusively in patients from the Middle East. More than one-half of the cases occurred in patients with no known underlying immunodeficiency. Mortality rates were high regardless of immune status. Therapy is not standardized, although the combination of amphotericin B, flucytosine, and itraconazole may improve survival rates. Newer azoles, such as voriconazole, also have a broad spectrum of activity against these fungi, although clinical experience is limited. Complete excision of brain lesions may provide better results than simple aspiration. An aggressive medical and surgical approach is warranted in treating these infections to optimize outcomes.
Comment on ‘standard operative temperatures of two desert rodents, Gerbillus allenbyi and Gerbillus pyramidum: The effects of morphology, microhabitat and environmental factors’

Abstract 1. 1. Because the effect of wind is to increase convective heat transfer, standard operative temperature, Tes, will always be less than operative temperature, Tc, when Tc is less than body temperature, Tb. If Tc is greater than Tb, then Tes will always exceed Tc. 2. 2. Standard operative temperature daa in a paper by Goodfriend, Ward and Subach [J. ther. Biol. 16, 157–166 (1991)] are suspect because Tes value presented exceed the values of Tc used to compute Tes, even though Te is well below Tb.
Ultrastructural studies on the developing neurohypophysis of the Pacific Treefrog, Hyla regilla☆

Abstract The differentiation of the hypothalamo-hypophysial neurosecretory system of the Pacific Treefrog Hyla regilla has been examined by correlated light and electron microscopy. Growing neurosecretory axons reach the diencephalic floor in close proximity to the “migrating” adenohypophysis at embryonic stage 23, approximately at the time of hatching. These axons, which already contain typical elementary neurosecretory granules and small vesicles, then grow caudad into the thin-walled infundibulum, reaching the site of the future neurohypophysis by larval stage 1. Not until active outgrowth of the nerve fibers is completed can the neurosecretory material within them be visualized with the light microscope. A striking synchrony exists between the rate of axon growth and the rate of adenohypophysial “migration.” Axons, usually containing small vesicles and small dense granules, penetrate the pars intermedia extensively, beginning with embryonic stage 24. Vascularization of the neurohypophysial area coincides with the arrival of neurosecretory axons at the site of the pars nervosa, just prior to larval stage I. As soon as these events have occurred, the pars nervosa is a miniature but ultrastructurally complete version of the adult neurohemal organ. Further development of the pars nervosa involves an increase in the number and size of axons, in number and possibly size of elementary neurosecretory granules, and in number of glial cells and capillaries. The median eminence differs from the pars nervosa in ultrastructure. Its axon terminals contain smaller neurosecretory granules (1000 A as opposed to 1500 A) and a greater abundance of small vesicles; the difference is reflected in the lesser intensity of paraldehyde fuchsin staining in the median eminence as compared to the pars nervosa. The characteristic terminals do not appear in large numbers in the median eminence until just before metamorphic climax. The observations are discussed in terms of the ontogeny of neurohypophysial function and the possibility of inductive relationships between various parts of the hypophysis.
Lactate dehydrogenase isolated from human liver mitochondria: its purification and partial biochemical characterization.

We have demonstrated that lactate dehydrogenase is not solely a cytosolic enzyme by the isolation and purification of the enzyme from the mitochondria of human liver. Treatment of the mitochondria with digitonin reveals the LD activity to be associated with the inner membrane—inner matrix and the outer membrane. The mitochondrial LD consists of two fractions separated by ion exchange and affinity chromatography. The first mitochondrial fraction, LD-Mt 1 , with isoelectric points of 9.8, 9.6, and 4.8, has subunit components of 14500 and 34000 daltons. The second mitochondrial fraction, LD-Mt 2 , is similar to cytosolic LD-5 with respect to both isoelectric points and subunit molecular weight. The first mitochondrial fraction, LD-Mt 1 , has physical characteristics previously associated with the isoenzyme LD-6.
Embedded market: challenges and opportunities

There is a convergence trend in the computing, communication and consumer markets and with a forecast of an additional 1 billion connected computing users by 2015, it is of high value to provide a common experience between the devices. Intel's vision of Compute Continuum will enable the users to realize the potential of a seamless cross-device experience with more consistency and accessibility to their information. The convergence trend and the Compute Continuum make System-on-Chip [SoC] a key ingredient for the embedded markets. At Intel Labs, we are focusing on delivering differentiating technology solutions to enable our business partners to successfully capture their targeted market segments. We are working on a variety of research that will enable modular system architecture and silicon technology breakthroughs for rapid customization and integration facilitating faster time-to-market. Intel's vision along with some technology challenges and possible solutions will be highlighted.
THE SIX MINUTE WALK DISTANCE AS AN INDICATOR OF FRAILTY AND FUNCTIONAL INCAPACITY IN ELDERLY HEART FAILURE PATIENTS

While cardiopulmonary exercise testing (CPX) is commonly used as the gold standard for functional evaluation in heart failure (HF) management, it may not reflect many pertinent aspects of physical function. We studied CPX and 6 minute walk distance (6MWD) in relation to strength and integrative
Three-dimensional SRAM design with on-chip access time measurement

An SRAM design in a 3D 0.18 µm silicon-on-insulator technology is presented. A novel delay-locked loop based access time measurement circuit was designed on-chip for accurately evaluating the 3D SRAM performance. Results show that a 32% improvement in the access time is gained by using 3D technology.
Role of the carboxy-terminal transactivation domain and active transcription in the ligand-induced and ligand-independent degradation of the mouse Ahb−1 receptor

To assess the importance of transactivation domains (TAD), DNA binding and transcription on the degradation of the AH receptor (AHR), Hepa-1 cells were pre-treated with actinomycin D (AD) or cycloheximide (CHX) and exposed to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). AD or CHX did not affect nuclear localization or DNA binding of the AHR but inhibited ligand-induced degradation. In contrast, AD or CHX did not inhibit geldanamycin (GA) induced degradation of the AHR. To assess the role of the COOH-terminal TAD in AHR degradation, stop codons were placed at nucleotide 1501 and 1921 of the Ahb−1 AHR coding region to generate AHR500 and AHR640. Stable cell lines were generated and exposed to TCDD. Cells expressing AHR500 did not induce CYP1A1 protein, but exhibited significant degradation of AHR500. Cells expressing AHR640 induced CYP1A1 protein to 50% of the level of cells expressing wild type AHR and exhibited significant degradation of AHR640. Importantly, AD and CHX did not inhibit the TCDD-induced degradation of either AHR500 and AHR640 and these receptors showed a more rapid profile of ligand-induced degradation compared to cells expressing wild type AHR. TCDD exposure to Hepa-1 cells with reduced aryl hydrocarbon receptor nuclear translocator (ARNT), showed ligand-induced degradation of the AHR that was not blocked by AD. However, AD inhibited TCDD-induced degradation when ARNT expression was restored. These results show that multiple mechanisms exist for the ligand and GA-induced degradation of the AHR and suggest that ligand-induced degradation can switch between two mechanisms depending on the presence of a functional TAD and the binding to DNA.
A Functional NSP4 Enterotoxin Peptide Secreted from Rotavirus-Infected Cells

Previous studies have shown that the nonstructural glycoprotein NSP4 plays a role in rotavirus pathogenesis by functioning as an enterotoxin. One prediction of the mechanism of action of this enterotoxin was that it is secreted from virus-infected cells. In this study, the media of cultured (i) insect cells infected with a recombinant baculovirus expressing NSP4, (ii) monkey kidney (MA104) cells infected with the simian (SA11) or porcine attenuated (OSU-a) rotavirus, and (iii) human intestinal (HT29) cells infected with SA11 were examined to determine if NSP4 was detectable. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis–Western blotting, immunoprecipitation and N-terminal amino acid sequencing identified, in the early media from virus-infected cells, a secreted, cleavage product of NSP4 with an apparent molecular weight of 7,000 that represented amino acids 112 to 175 (NSP4 aa112–175). The secretion of NSP4 aa112–175 was not affected by treatment of cells with brefeldin A but was abolished by treatment with nocodazole and cytochalasin D, indicating that secretion of this protein occurs via a nonclassical, Golgi apparatus-independent mechanism that utilizes the microtubule and actin microfilament network. A partial gene fragment coding for NSP4 aa112–175 was cloned and expressed using the baculovirus-insect cell system. Purified NSP4 aa112–175 increased intracellular calcium mobilization in intestinal cells when added exogenously, and in insect cells when expressed endogenously, similarly to full-length NSP4. NSP4 aa112–175 caused diarrhea in neonatal mice, as did full-length NSP4. These results indicate that NSP4 aa112–175 is a functional NSP4 enterotoxin peptide secreted from rotavirus-infected cells.
Endothelial cell monolayer formation: effect of substrate and fluid shear stress.

The formation of an endothelial cell (EC) monolayer is one critical factor in the development of a tissue engineered vascular graft. One potential method of endothelialization is the migration of native ECs from the surrounding blood vessel onto the newly implanted graft. In the present study, in vitro experiments were performed to investigate the potential of ECs to migrate on a tissue-engineered blood vessel wall model (TEWM) and form a new monolayer. The TEWM was composed of a three-dimensional, type I collagen matrix seeded with smooth muscle cells. The potential of ECs to form new monolayer was evaluated in the absence and presence of fluid shear stress (10 dynes/cm2). The monolayer formation on the TEWM was compared to a control, two-dimensional substrate of glass coated with type I collagen. Results from these studies showed that EC monolayer formation was inhibited on the TEWM in comparison to glass coated with collagen. This correlated with an inhibition of proliferation on the TEWM. The applicat...
Molecular Insights into the Pathogenesis of Alzheimer's Disease and Its Relationship to Normal Aging

Alzheimer's disease (AD) is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age), Alz (Alzheimer), Inflame (inflammation), and NdStress (neurodegenerative stress). BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT) transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression.
Effect of gamma-chlordane on synchronized lymphoma cells and inhibition of cell division.

BOTH acute and chronic toxicities are exhibited by human and murine cells grown in culture in the presence of chlorinated hydrocarbon pesticides1–5. To learn more about the underlying mechanisms responsible for the acute toxicity, we have examined the effects of γ-chlordane on cell division and DNA synthesis utilizing synchronized mouse leukaemia cells (L-5178Y) grown in suspension culture. Synchronized cells provide a means of amplifying a toxic response which ultimately should provide significant clues to the nature of the molecular mechanisms of chlordane toxicity.
Calculating tissue shear modulus and pressure by 2D Log-Elastographic methods

Shear modulus imaging, often called elastography, enables detection and characterization of tissue abnormalities. In this paper the data is two displacement components obtained from successive MR or ultrasound data sets acquired while the tissue is excited mechanically. A 2D plane strain elastic model is assumed to govern the 2D displacement, u. The shear modulus, μ, is unknown and whether or not the first Lame parameter, λ, is known the pressure p = λ∇ · u which is present in the plane strain model cannot be measured and is unreliably computed from measured data and can be shown to be an order one quantity in the units kPa. So here we present a 2D Log-Elastographic inverse algorithm that: (1) simultaneously reconstructs the shear modulus, μ, and p, which together satisfy a first order partial differential equation system, with the goal of imaging μ; (2) controls potential exponential growth in the numerical error; and (3) reliably reconstructs the quantity p in the inverse algorithm as compared to the same quantity computed with a forward algorithm. This work generalizes the Log-Elastographic algorithm in [20] which uses one displacement component, is derived assuming the component satisfies the wave equation, and is tested on synthetic data computed with the wave equation model. The 2D Log-Elastographic algorithm is tested on 2D synthetic data and 2Din-vivo data from Mayo Clinic. We also exhibit examples to show that the 2D Log-Elastographic algorithm improves the quality of the recovered images as compared to the Log-Elastographic and Direct Inversion algorithms.
An Unfavourable Situation: NATO and the Conventional Balance

The view, long and widely held, that NATO conventional military forces are inferior to Warsaw Pact forces is one of the most important factors shaping post-war history. It influenced the size and nature of the American military commitment to Europe. It is at the heart of the ‘extended deterrence’ strategy, in which the US commitment to use nuclear weapons in the defence of Europe offsets the Warsaw Pact’s perceived conventional superiority. The notion of Western inferiority runs through much of today’s public debate on security policy — the INF Treaty, the future of nuclear and conventional arms control, US and Allied defence programmes, the burden-sharing debate, and so forth. These debates have spawned a new round of discussions on the nature of the conventional military balance in Europe and will affect US and Western policies.