bluuebunny/crossref_metadata_2025 huggingface dataset:
BEING UNCERTAIN: THE RELATIONSHIP BETWEEN ENTREPRENEURIAL ORIENTATION AND ENVIRONMENTAL UNCERTAINTY
Authors: WEAVER K. MARK , DICKSON PAT H. , GIBSON BRIAN , TURNER ANDREW
Published: November 2004

The manner in which the key managers of entrepreneurial firms perceive the environment of the firm has important implications for decisions regarding organizational structure, processes and performance. Entrepreneurial behavior has traditionally been characterized as one type of strategic response to uncertain environments. This research takes a unique position in exploring how the entrepreneurial orientation of the firm's key manager may in fact influence managerial perceptions of the environment. Utilizing survey data drawn from more than 800 key managers in three countries this study proposes and tests a model of perceived uncertainty. The results suggest that the greater the entrepreneurial orientation of the key manager the more likely he or she is to characterize the environment of the firm as uncertain. Although this relationship holds true in general the results also suggest that there are strong differences in the relationship across countries and industries and that certain firm characteristics have a potential impact on managerial perceptions.
TECHNOLOGY TRANSFER FROM GOVERNMENT LABS TO ENTREPRENEURS
Authors: WALSH STEPHEN T. , KIRCHHOFF BRUCE A.
Published: November 2004

The transfer of technologies from government operated research laboratories to commercial firms is a difficult and complicated process. Corporate research and development agreements, intellectual property licenses and other agreements are keys to this process as they offer intellectual property protection to the technology creator. But the high costs of negotiating such agreements make them prohibitively expensive for many emerging entrepreneurial firms (Steffensen, et. al, 2000). These arrangements work well for large firms because large firms have adequate funding. Moreover, they are primarily interested in evolutionary technologies that lead to rather quick market penetration and rapid returns on investment in intellectual property agreements (Christensen, 1997). Independent entrepreneurial firms, however, often focus on disruptive technologies and discontinuous innovations that take much longer to achieve market acceptance and revenue generation (Christensen, 1997).

Empirical evidence shows that small firms are more efficient innovators and develop more "major" innovations compared to large firms (Futures Group, 1984; Gellman, 1974). Thus, ineffective technology transfer from government labs to small firms may cause lower rates of innovation for society thereby reducing economic growth below its potential.

This technology transfer problem has been recognized by Sandia National Laboratories and it has responded by creating the SAMPLES program. Herein, we describe the differences between disruptive and evolutionary technologies and create a model that exemplifies the important characteristics to technology transfer. Next, we describe the SAMPLES technology transfer model that began in 1996, show how implementation of this model leads to commercialization of disruptive technologies and report empirical evidence of its success with nearly 100 entrepreneurial firms over the last four years. Success of the SAMPLES program suggests that it provides a useful model that may be replicated in other nations that seek to commercialize government laboratory research.
A TAXONOMY OF SME DEVELOPMENT SCHEMES
Authors: TOH THIAN SER
Published: November 2004

"Small and medium enterprises (SMEs) form the largest pool of enterprises in most countries. Asian governments have developed a plethora of SME assistance schemes but not many do not appear to be effective. One reason for this may be a potential clash in policy objectives. This paper develops a taxonomy for classifying SME assistance schemes based on four broad policy orientations - welfare, efficiency, building champions and transactioncost-reduction. This taxonomy may be used as a basis for the development of propositions which can be tested so that a tool can be developed for evaluating the effectiveness of government initiatives in the development of SMEs."
NEW VENTURES AS SUPPLIERS: THE BUILDING OF TRUST WITH INDUSTRIAL CUSTOMERS
Authors: SANNER LEIF
Published: November 2004

The new venture starts in an equivocal situation. To use and build trusted relationships with external actors, notably customers in spe, is an important way for the entrepreneur to establish business. In an inductive in-depth case study between entrepreneurs and customers, trust was studied. For two business start-ups the entrepreneurs' building and use of trust in action processes between the new ventures and some of their customers was investigated covering 5 years. Using a frame of reference concerning new business trust, trustbuilding in action processes is identified in interviews. Patterns of trustbuilding are summarised, conclusions concerning trustbuilding in the cases are presented and discussed. Some possible contributions for practice and theory are outlined.
A RISK MANAGEMENT MODEL FOR PRESERVATION OF FAMILY BUSINESS
Authors: CHIN YEE WAH , CHAN PATRICK K. P.
Published: November 2004

Despite the psychological and material advantages of maintaining a family business, statistic on sustained growth are grim. This paper examines why it is essential for a family business to actively plan for the management succession process using a Risk Management Model (RMM). The RMM identifies the succession exposures in the family business, evaluates the impact of the identified succession exposures, and helps to effectively control the succession exposures.
PARTNERSHIPS — A KEY TO GROWTH IN SMALL BUSINESS
Authors: MAZZAROL TIM
Published: November 2004

The conventional image of the small business owner is that of a highly independent individual, taking risks and 'doing it tough' with limited assistance from others. However, research conducted in the United Kingdom and Australia with high performance small firms suggest that this is not so. A multivariate data analysis of the relationship between business management practice and sales growth performance identified the importance of partnering. This refers to the process of working in partnership with people who affect the business. Partnering involves creating and maintaining partnerships with everyone who affects your business. Working in partnership involves the creative talents and energies of everyone who can affect your business. The effect is that everyone, from staff through to supplier and customers, works together for mutual gain. These findings suggest that the owner of a small business needs to view himself or herself less as a lonely, isolated battler and more as someone who can gain from partnering. A willingness to seek strategic alliances can prove a valuable source of potential growth for small firms.
WAL-MART INTO THE UK
Authors: ARNOLD STEPHEN J. , FERNIE JOHN
Published: November 2004

The purpose of this case is to assess the long-term opportunity for Wal-Mart in the UK market. To make this assessment, the potential reaction of consumers, employees and competitors must be considered. The likely method of market entry must also be assessed.
AN ACTIVITY-PRODUCT AFFILIATION NETWORK APPROACH TO STUDY PRODUCT CONVERGENCE OPPORTUNITIES
Authors: ANAM FAISAL , ALLADA VENKAT
Published: November 2004

A vast majority of new products in the consumer electronics market are marked by improvements to contemporary products. It is reported that companies spend billions of dollars on product convergence projects in an effort to combine existing products. In this paper, a systematic methodology to explore new product convergence opportunities is presented. The methodology consists of the following major steps: (1) Create an activity-product affiliation network and then extract the product network in which products are related to each other by virtue of being affiliated to the same activity. (2) Explore the product network to determine the aristocrat products (based on the degree of product connectivity) and products that are affiliated to two or more activities (called bridge products). (3) Scrutinize and retain products that are both aristocrats and bridge products (called critical bridge products) based on their market potential and network stability. (4) Investigate convergence opportunities for these critical bridge products using the Analytical Hierarchical Process (AHP) model and local centrality method. The application of the proposed method is demonstrated using an example case that consists of 16 activities and 232 different consumer products.
Hypertrophy, increased ejection fraction, and reduced Na-K-ATPase activity in phospholemman-deficient mice
Authors: Jia Li-Guo , Donnet Claudia , Bogaev Roberta C. , Blatt Rebecca J. , McKinney Cindy E. , Day Kathleen H. , Berr Stuart S. , Jones Larry R. , Moorman J. Randall , Sweadner Kathleen J. , Tucker Amy L.
Published: November 2004

Phospholemman (FXYD1), a 72-amino acid transmembrane protein abundantly expressed in the heart and skeletal muscle, is a major substrate for phosphorylation in the cardiomyocyte sarcolemma. Biochemical, cellular, and electrophysiological studies have suggested a number of possible roles for this protein, including ion channel modulator, taurine-release channel, Na+/Ca2+exchanger modulator, and Na-K-ATPase-associated subunit. We have generated a phospholemman-deficient mouse. The adult null mice exhibited increased cardiac mass, larger cardiomyocytes, and ejection fractions that were 9% higher by magnetic resonance imaging compared with wild-type animals. Notably, this occurred in the absence of hypertension. Total Na-K-ATPase activity was 50% lower in the phospholemman-deficient hearts. Expression (per unit of membrane protein) of total Na-K-ATPase was only slightly diminished, but expression of the minor α2-isoform, which has been specifically implicated in the control of contractility, was reduced by 60%. The absence of phospholemman thus results in a complex response, including a surprisingly large reduction in intrinsic Na-K-ATPase activity, changes in Na-K-ATPase isoform expression, increase in ejection fraction, and increase in cardiac mass. We hypothesize that a primary effect of phospholemman is to modulate the Na-K-ATPase and that its reduced activity initiates compensatory responses.
Assessment of left ventricular diastolic suction in dogs using wave-intensity analysis
Authors: Wang Zhibin , Jalali Fereshteh , Sun Yi-Hui , Wang Jiun-Jr , Parker Kim H. , Tyberg John V.
Published: November 2004

Two apparently different types of mechanisms have emerged to explain diastolic suction (DS), that property of the left ventricle (LV) that tends to cause it to refill itself during early diastole independent of any force from the left atrium (LA). By means of the first mechanism, DS depends on decreased elastance [e.g., the relaxation time constant (τ)] and, by the second, end-systolic volume (VLVES). We used wave-intensity analysis (WIA) to measure the total energy transported by the backward expansion wave ( IW−) during LV relaxation in an attempt to reconcile these mechanisms. In six anesthetized, open-chest dogs, we measured aortic, LV (PLV), LA (PLA), and pericardial pressures and LV volume by orthogonal ultrasonic crystals. Mitral velocity was measured by Doppler echocardiography, and aortic velocity was measured by an ultrasonic flow probe. Heart rate was controlled by pacing, VLVES by volume loading, and τ by isoproterenol or esmolol administration. IW− was found to be inversely related to τ and VLVES. Our measure of DS, the energy remaining after mitral valve opening, IW−DS, was also found to be inversely related to τ and VLVES and was ∼10% of the total “aspirating” energy generated by LV relaxation (i.e., IW−). The size of the Doppler (early filling) E wave depended on IW−DS in addition to IW+, the energy associated with LA decompression. We conclude that the energy of the backward-going wave generated by the LV during relaxation depends on both the rate at which elastance decreases (i.e., τ) and VLVES. WIA provides a new approach for assessing DS and reconciles those two previously proposed mechanisms. The E wave depends on DS in addition to LA decompression.
Met5-enkephalin-induced cardioprotection occurs via transactivation of EGFR and activation of PI3K
Authors: Cao Zhiping , Liu Lijuan , Van Winkle Donna M.
Published: November 2004

Our previous studies indicated that opioid-induced cardioprotection occurs via activation of mitochondrial ATP-sensitive K+ (KATP) channels. However, other elements of the Met5-enkephalin (ME) cardioprotection pathway are not fully characterized. In the present study, we investigated the role of tyrosine kinase, MAPK, and phosphatidylinositol 3-kinase (PI3K) signaling in ME-induced protection. Ca2+-tolerant, adult rabbit cardiomyocytes were isolated by collagenase digestion and subjected to simulated ischemia for 180 min. ME was administered 15 min before the 180 min of simulated ischemia; blockers were administered 15 min before ME. Cell death was assessed by trypan blue as a function of time. The epidermal growth factor receptor (EGFR) kinase inhibitor AG-1478 (250 nM) blocked ME-induced protection, but the inactive analog AG-9 (100 μM) did not. Treatment with herbimycin (1 μM) completely eliminated ME-induced protection. To verify that ME activates EGFR and to determine the involvement of Src, Western blotting of EGFR was performed after ME administration with and without herbimycin A. ME resulted in herbimycin-sensitive robust phosphorylation of EGFR at Tyr992 and Tyr1068. Administration of the selective MAPK inhibitor PD-98059 (10 nM) and the specific MEK1/2 inhibitor U-0126 (10 μM) also inhibited ME-induced cardioprotection. ME-induced ERK1/2 phosphorylation was significantly reduced by PD-98059, the EGFR kinase inhibitor PD-153035 (10 μM), and chelerythrine (2 μM). The PI3K inhibitor LY-294002 (20 μM) abrogated ME-induced protection, and ME-induced Akt phosphorylation at Ser473 was suppressed by LY-294002, PD-153035, and chelerythrine. We conclude that ME-induced cardioprotection is mediated via Src-dependent EGFR transactivation and activation of the PI3K and MAPK pathways.
Mitochondrial membrane potential modulates regulation of mitochondrial Ca2+in rat ventricular myocytes
Authors: Saotome Masao , Katoh Hideki , Satoh Hiroshi , Nagasaka Shiro , Yoshihara Shu , Terada Hajime , Hayashi Hideharu
Published: November 2004

Although recent studies focused on the contribution of mitochondrial Ca2+to the mechanisms of ischemia-reperfusion injury, the regulation of mitochondrial Ca2+under pathophysiological conditions remains largely unclear. By using saponin-permeabilized rat myocytes, we measured mitochondrial membrane potential (ΔΨm) and mitochondrial Ca2+concentration ([Ca2+]m) at the physiological range of cytosolic Ca2+concentration ([Ca2+]c; 300 nM) and investigated the regulation of [Ca2+]mduring both normal and dissipated ΔΨm. When ΔΨmwas partially depolarized by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP, 0.01–0.1 μM), there were dose-dependent decreases in [Ca2+]m. When complete ΔΨmdissipation was achieved by FCCP (0.3–1 μM), [Ca2+]mremained at one-half of the control level despite no Ca2+influx via the Ca2+uniporter. The ΔΨmdissipation by FCCP accelerated calcein leakage from mitochondria in a cyclosporin A (CsA)-sensitive manner, which indicates that ΔΨmdissipation opened the mitochondrial permeability transition pore (mPTP). After FCCP addition, inhibition of the mPTP by CsA caused further [Ca2+]mreduction; however, inhibition of mitochondrial Na+/Ca2+exchange (mitoNCX) by a Na+-free solution abolished this [Ca2+]mreduction. Cytosolic Na+concentrations that yielded one-half maximal activity levels for mitoNCX were 3.6 mM at normal ΔΨmand 7.6 mM at ΔΨmdissipation. We conclude that 1) the mitochondrial Ca2+uniporter accumulates Ca2+in a manner that is dependent on ΔΨmat the physiological range of [Ca2+]c; 2) ΔΨmdissipation opens the mPTP and results in Ca2+influx to mitochondria; and 3) although mitoNCX activity is impaired, mitoNCX extrudes Ca2+from the matrix even after ΔΨmdissipation.
Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction
Authors: Smith Lauren L. , Kukielka Monica , Billman George E.
Published: November 2004

Heart rate recovery after exercise, thought to be related to cardiac parasympathetic tone, has been shown to be a prognostic tool for all-cause mortality. However, the relationship between this variable and confirmed susceptibility to ventricular fibrillation (VF) has not been established. Therefore, myocardial ischemia was induced with a 2-min occlusion of the left circumflex artery during the last minute of exercise in mongrel dogs with myocardial infarction ( n = 105 dogs). VF was induced in 66 animals (susceptible), whereas the remaining 39 dogs had no arrhythmias (resistant). On a previous day, ECG was recorded and a time-series analysis of heart rate variability was measured 30, 60, and 120 s after submaximal exercise (treadmill running). The heart rate recovery was significantly greater in resistant dogs than in susceptible dogs at all three times, with the most dramatic difference at the 30-s mark (change from maximum: 48.1 ± 3.6 beats/min, resistant dogs; 31.0 ± 2.2 beats/min, susceptible dogs). Correspondingly, indexes of parasympathetic tone increased to a significantly greater extent in resistant dogs at 30 and 60 s after exercise. These differences were eliminated by atropine pretreatment. When considered together, these data suggest that resistant animals exhibit a more rapid recovery of vagal activity after exercise than those susceptible to VF. As such, postexercise heart rate recovery may help identify patients with a high risk for VF following myocardial infarction.
Endogenous endothelin attenuates the pressor response to acute environmental stress via the ETAreceptor
Authors: D’Angelo Gerard , Pollock Jennifer S. , Pollock David M.
Published: November 2004

Clinical studies have documented an abrupt rise in plasma endothelin-1 (ET-1) coincident with an increase in mean arterial pressure (MAP) during the response to acute stress. We therefore examined the ETAand ETBreceptor-dependent effects of ET-1 on the pressor response to acute environmental stress in ET-1-dependent hypertension. Stress was induced by administration of air jet pulses (3 min) in ETBreceptor-deficient (ETBsl/sl) rats fed normal salt (NS; 0.8% NaCl), high salt (HS; 8% NaCl), and HS plus the ETAreceptor antagonist ABT-627 (5 mg·kg−1·day−1) on successive weeks. MAP was chronically monitored by telemetry. Total pressor response (area under the curve) was significantly reduced in ETBsl/sl rats maintained on a HS vs. NS diet [−6.8 mmHg (SD 18.7) vs. 29.3 mmHg (SD 8.1) × 3 min, P < 0.05]. Conversely, the total pressor response was augmented in both wild-type [34.2 mmHg (SD 29.2) × 3 min, P < 0.05 vs. NS] and ETBsl/sl rats [49.1 mmHg (SD 11.8) × 3 min, P < 0.05 vs. NS] by ABT-627. Blockade of ETBreceptors in Sprague-Dawley rats caused an increase in basal MAP that was enhanced by HS and lowered by mixed ETA/ETBreceptor antagonism; none of these treatments, however, had any effect on the pressor response. These data demonstrate that increasing endogenous ET-1 suppresses the pressor response to acute stress through ETAreceptor activation in a genetic model of ET-1-dependent hypertension. These results are consistent with reports that ET-1 can attenuate sympathetically mediated responses.
C-reactive protein does not relax vascular smooth muscle: effects mediated by sodium azide in commercially available preparations
Authors: Swafford Albert N. , Bratz Ian N. , Knudson Jarrod D. , Rogers Paul A. , Timmerman Jennifer M. , Tune Johnathan D. , Dick Gregory M.
Published: November 2004

C-reactive protein (CRP), an acute-phase protein and newly recognized indicator of cardiovascular risk, may have direct actions on the vascular wall. Previous studies suggest that CRP is a vasodilator that activates smooth muscle K+ channels. We examined the reported vasoactive properties of CRP and further explored its mechanisms of action. CRP decreased blood pressure in rats and increased coronary flow in open-chest dogs at a constant coronary perfusion pressure. CRP relaxed rat aortic rings and mesenteric small arteries that were contracted with phenylephrine. Relaxation was not affected by endothelial denudation or inhibition of nitric oxide (NO) synthase but was blocked by inhibition of soluble guanylate cyclase or K+ channels. CRP solutions remained effective, i.e., elicited vasodilation, even after boiling or enzymatic digestion, which suggests the presence of a nonprotein contaminant. Sodium azide (NaN3, 0.1%) is the preservative used for commercially available CRP and a potential source of NO. NaN3 elicited the same cardiovascular effects as CRP preparations at equal concentrations, and its actions were blocked by inhibition of guanylate cyclase and K+ channels. NaN3-free CRP, prepared by gel-filtration centrifugation and confirmed by electrophoresis, had no effect on vascular tone. Inhibition of vascular smooth muscle catalase with 3-amino-1,2,4-triazole completely prevented the effects of NaN3 and NaN3-containing CRP solutions. We demonstrate that the acute vasoactive properties of commercially available CRP preparations are attributable to NaN3 (and subsequent production of NO by catalase); therefore, this study suggests a reappraisal of the acute role of CRP in regulating vascular tone.
Protease-activated receptor-1 in human lung fibroblasts mediates a negative feedback downregulation via prostaglandin E2
Authors: Sokolova Elena , Grishina Zoryana , Bühling Frank , Welte Tobias , Reiser Georg
Published: November 2004

Among the four protease-activated receptors (PARs), PAR-1 plays an important role in normal lung functioning and in the development of lung diseases, including fibrosis. We compared the expression and functional activity of PARs in normal and fibrotic human lung fibroblasts. Both normal and fibrotic cells express PAR-1, -2, and -3, with PAR-2 showing the lowest level. There was no significant difference between normal and fibrotic fibroblasts in expression levels of PAR-1 and PAR-3, whereas a fourfold higher expression level of PAR-2 was observed in fibrotic cells compared with normal cells. Ca2+imaging studies revealed apparently only PAR-1-induced Ca2+signaling in lung fibroblasts. PAR-1 agonists, thrombin and synthetic activating peptide, induced concentration-dependent Ca2+mobilization with EC50values of 5 nM and 1 μM, respectively. The neutrophil protease cathepsin G produced a transient Ca2+response followed by disabling PAR-1, whereas elastase did not affect Ca2+level. PAR-1 activation by thrombin or receptor-activating peptide downregulated expression of all three PARs in lung fibroblasts, with maximal effect at 3–6 h, whereas expression returned toward basal level after 24 h. Furthermore, PAR-1 agonists dose dependently increased PGE2secretion from lung fibroblasts and induction of cyclooxygenase-2 expression. We then found that PGE2downregulated expression of all three PARs. The effect of PGE2was continuously growing with time. Furthermore, PGE2exerts its effect through the EP2 receptor that was confirmed using the selective EP2 agonist butaprost. This novel autocrine feedback mechanism of PGE2in lung fibroblasts seems to be an important regulator in lung physiology and pathology.
IL-13 may mediate allergen-induced hyperresponsiveness independently of IL-5 or eotaxin by effects on airway smooth muscle
Authors: Eum Seok-Yong , Maghni Karim , Tolloczko Barbara , Eidelman David H. , Martin James G.
Published: November 2004

IL-13 is a mediator of allergen-induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate whether eotaxin and IL-5 were implicated in the effects of IL-13 on allergen-induced AHR or whether IL-13 may exert its effects through direct actions on airway smooth muscle (ASM). To study this question airway inflammation and AHR were induced in mice by sensitization and subsequent challenge on three successive days with ovalbumin. A monoclonal anti-IL-13 antibody administered before each challenge significantly reduced AHR without affecting airway eosinophilia. No changes of mRNA in BAL and lung tissues or protein levels in BAL of IL-5 or eotaxin were found following anti-IL-13 treatment. Combined injection of monoclonal anti-IL-5 and antieotaxin antibodies before each antigen challenge blocked airway eosinophilia but failed to reduce AHR. IL-13 induced calcium transients in cultured murine ASM cells and augmented the calcium and contractile responses of these cells to leukotriene D4. These results suggest that IL-13 plays an important role in allergen-induced AHR and is important in the early phases of the inflammatory process. Its effects on AHR are mediated independently of IL-5 and eotaxin and may involve a direct effect on ASM to augment its responsiveness.
UT-B1 urea transporter is expressed along the urinary and gastrointestinal tracts of the mouse
Authors: Lucien N. , Bruneval P. , Lasbennes F. , Belair M.-F. , Mandet C. , Cartron J.-P. , Bailly P. , Trinh-Trang-Tan M.-M.
Published: November 2004

Selective transporters account for rapid urea transport across plasma membranes of several cell types. UT-B1 urea transporter is widely distributed in rat and human tissues. Because mice exhibit high urea turnover and are the preferred species for gene engineering, we have delineated UT-B1 tissue expression in murine tissues. A cDNA was cloned from BALB/c mouse kidney, encoding a polypeptide that differed from C57BL/6 mouse UT-B1 by one residue (Val-8-Ala). UT-B1 mRNA was detected by RT-PCR in brain, kidney, bladder, testis, lung, spleen, and digestive tract (liver, stomach, jejunum, colon). Northern blotting revealed seven UT-B1 transcripts in mouse tissues. Immunoblots identified a nonglycosylated UT-B1 protein of 29 kDa in most tissues and of 36 and 32 kDa in testis and liver, respectively. UT-B1 protein of gastrointestinal tract did not undergo N-glycosylation. Immunohistochemistry and in situ hybridization localized UT-B1 in urinary tract urothelium (papillary surface, ureter, bladder, and urethra), prominently on plasma membranes and restricted to the basolateral area in umbrella cells. UT-B1 was found in endothelial cells of descending vasa recta in kidney medulla and in astrocyte processes in brain. Dehydration induced by water deprivation for 2 days caused a tissue-specific decrease in UT-B1 abundance in the urinary bladder and the ureter.
Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin activity but does not activate caspase-3
Authors: Wei Wei , Fareed Moin U. , Evenson Amy , Menconi Michael J. , Yang Hongmei , Petkova Victoria , Hasselgren Per-Olof
Published: November 2004

We examined the influence of sepsis on the expression and activity of the calpain and caspase systems in skeletal muscle. Sepsis was induced in rats by cecal ligation and puncture (CLP). Control rats were sham operated. Calpain activity was determined by measuring the calcium-dependent hydrolysis of casein and by casein zymography. The activity of the endogenous calpain inhibitor calpastatin was measured by determining the inhibitory effect on calpain activity in muscle extracts. Protein levels of μ- and m-calpain and calpastatin were determined by Western blotting, and calpastatin mRNA was measured by real-time PCR. Caspase-3 activity was determined by measuring the hydrolysis of the fluorogenic caspase-3 substrate Ac-DEVD-AMC and by determining protein and mRNA expression for caspase-3 by Western blotting and real-time PCR, respectively. In addition, the role of calpains and caspase-3 in sepsis-induced muscle protein breakdown was determined by measuring protein breakdown rates in the presence of specific inhibitors. Sepsis resulted in increased muscle calpain activity caused by reduced calpastatin activity. In contrast, caspase-3 activity, mRNA levels, and activated caspase-3 29-kDa fragment were not altered in muscle from septic rats. Sepsis-induced muscle proteolysis was blocked by the calpain inhibitor calpeptin but was not influenced by the caspase-3 inhibitor Ac-DEVD-CHO. The results suggest that sepsis-induced muscle wasting is associated with increased calpain activity, secondary to reduced calpastatin activity, and that caspase-3 activity is not involved in the catabolic response to sepsis.
On the Banach algebra ℬ(lp(α))
Authors: de Malafosse Bruno
Published: November 2004

We give some properties of the Banach algebra of bounded operators
ℬ(lp(α))
for 1 ≤ p ≤ ∞,
where lp(α) = (1/α) −1∗lp. Then we deal with the continued fractions and give some properties of the operator Δh
for h > 0
or integer greater than or equal to one mapping lp(α)
into itself for p ≥ 1
real. These results extend, among other things, those
concerning the Banach algebra Sα
and some results on the continued fractions.
Antivirals for the Treatment of Chronic Hepatitis B: Current and Future Options
Authors: Humphries Jason C. , Dixon Jonathan S.
Published: November 2004

Despite effective vaccination programmes, new hepatitis B virus (HBV) infections remain common and there are many millions of individuals already infected. Therapeutic agents are needed to reverse existing liver disease and prevent future disease progression. This article reviews recently published clinical data on the two currently available antivirals for the treatment of chronic hepatitis B infection, lamivudine and adefovir dipivoxil. Lamivudine, a nucleoside analogue, is currently the only licensed antiviral for the treatment of chronic hepatitis B in Asia. Extensive clinical trials have shown that lamivudine is effective and well tolerated in a wide range of patients. YMDD variants have been identified in some patients with reduced sensitivity to lamivudine after extended therapy. Adefovir dipivoxil, a nucleotide analogue, will soon be commercially available in Asia. Adefovir dipivoxil 10 mg is well tolerated and is as effective as lamivudine in reducing serum HBV DNA and alanine aminotransaminase levels and increasing seroconversion in patients with hepatitis B e antigen. No adefovir-resistant mutants have been reported during 48-week clinical trials. The addition of adefovir dipivoxil to ongoing lamivudine therapy, in patients with YMDD variants and a reduced response to lamivudine, leads to significant inhibition of viral replication and improvement in liver function after 1 year of therapy.
The Alignment Template Approach to Statistical Machine Translation
Authors: Och Franz Josef , Ney Hermann
Published: November 2004

A phrase-based statistical machine translation approach — the alignment template approach — is described. This translation approach allows for general many-to-many relations between words. Thereby, the context of words is taken into account in the translation model, and local changes in word order from source to target language can be learned explicitly. The model is described using a log-linear modeling approach, which is a generalization of the often used source-channel approach. Thereby, the model is easier to extend than classical statistical machine translation systems. We describe in detail the process for learning phrasal translations, the feature functions used, and the search algorithm. The evaluation of this approach is performed on three different tasks. For the German-English speech Verbmobil task, we analyze the effect of various system components. On the French-English Canadian Hansards task, the alignment template system obtains significantly better results than a single-word-based translation model. In the Chinese-English 2002 National Institute of Standards and Technology (NIST) machine translation evaluation it yields statistically significantly better NIST scores than all competing research and commercial translation systems.
A Probabilistic Framework for Region-Specific Remodeling of Dendrites in Three-Dimensional Neuronal Reconstructions
Authors: Narayanan Rishikesh , Narayan Anusha , Chattarji Sumantra
Published: November 2004

Dendritic arborization is an important determinant of single-neuron function as well as the circuitry among neurons. Dendritic trees undergo remodeling during development, aging, and many pathological conditions, with many of the morphological changes being confined to certain regions of the dendritic tree. In order to analyze the functional consequences of such region-specific dendritic remodeling, it is essential to develop techniques that can systematically manipulate three-dimensional reconstructions of neurons. Hence, in this study, we develop an algorithm that uses statistics from precise morphometric analyses to systematically remodel neuronal reconstructions. We use the distribution function of the ratio of two normal distributed random variables to specify the probabilities of remodeling along various regions of the dendritic arborization. We then use these probabilities to drive an iterative algorithm for manipulating the dendritic tree in a region-specific manner. As a test, we apply this framework to a well-characterized example of dendritic remodeling: stress-induced dendritic atrophy in hippocampal CA3 pyramidal cells. We show that our pruning algorithm is capable of eliciting atrophy that matches biological data from rodent models of chronic stress.
Limited Field of View of Head-Mounted Displays Is Not the Cause of Distance Underestimation in Virtual Environments
Authors: Knapp Joshua M. , Loomis Jack M.
Published: November 2004

Observers binocularly viewed a target placed in a large open field under two viewing conditions: unrestricted field of view and reduced field of view, as effected using a simulated head-mounted display. Observers indicated the perceived distance of the target, which ranged from 2 to 15 m, using both verbal report and blind walking. For neither response was there a reliable effect of limiting the field of view on the perception of distance. This result indicates that the significant underperception of distance observed in several studies on distance perception in virtual environments is not caused by the limited field of view of the head-mounted display.
The Importance of Stereo and Eye-Coupled Perspective for Eye-Hand Coordination in Fish Tank VR
Authors: Arsenault Roland , Ware Colin
Published: November 2004

It is possible to simulate a high-quality virtual environment with viewpoint-controlled perspective, high-quality stereo, and a sense of touch obtained with the PHANToM force feedback device using existing “fish tank VR” technologies. This enables us to investigate the importance of different depth cues and touch using higher quality visual display than is possible with more immersive technologies. Prior work on depth perception suggests that different depth cues are important depending on the task performed. A number of studies have shown that motion parallax is more important than stereopsis in perceiving 3D patterns, but other studies suggest that stereopsis should be critically important for visually guided reaching. A Fitts' Law tapping task was used to investigate the relative importance of stereo and head tracking in visually guided hand movements. It allowed us to examine the intertap intervals following a head movement in order to look for evidence of rapid adaptation to a misplaced head position. The results show that stereo is considerably more important than eye-coupled perspective for this task, and that the benefits increase as task difficulty increases. Disabling stereo increased mean intertap intervals by 33%, while disabling head tracking produced only an 11% time increase. However, we failed to find the expected evidence for adaptation during the series of taps. We conclude by discussing the theoretical and practical implications of the results.
The Role of Graphical Feedback About Self-Movement when Receiving Objects in an Augmented Environment
Authors: Mason Andrea H. , MacKenzie Christine L.
Published: November 2004

This work explored how the presence of graphical information about self-movement affected reach-to-grasp movements in an augmented environment. Twelve subjects reached to grasp objects that were passed by a partner or rested on a table surface. Graphical feedback about self-movement was available for half the trials and was removed for the other half. Results indicated that removing visual feedback about self-movement in an object-passing task dramatically affected both the receiver's movement to grasp the object and the time to transfer the object between partners. Specifically, the receiver's deceleration time, and temporal and spatial aspects of grasp formation, showed significant effects. Results also indicated that the presence of a graphic representation of self-movement had similar effects on the kinematics of reaching to grasp a stationary object on a table as for one held by a stationary or moving partner. These results suggest that performance of goal-directed movements, whether to a stationary object on a table surface or to objects being passed by a stationary or moving partner, benefits from a crude graphical representation of the finger pads. The role of providing graphic feedback about self-movement is discussed for tasks requiring precision. Implications for the use of kinematic measures in the field of Human-Computer Interaction (HCI) are also discussed.
Child Bodies, Blessed Bodies: the Contest Between Christian Virginity and Confucian Chastity
Authors: Menegon Eugenio
Published: November 2004

In late imperial China chastity of a widowed or betrothed woman, rather than virginity per se, was considered the core female virtue in social practice, in literary discourse, and in law. However, religious chastity as offered in Buddhism and other Chinese religious traditions was a way for women to evade the strictures of married life. This helps explain why, when introduced in the seventeenth century by Spanish Dominican friars, the concept of virginity as a prerequisite for consecrated religious life found enthusiastic acceptance among some women in Fujian province. To legitimize virginity as a virtue and a perpetual state of life for some Chinese women, missionaries and their converts ingeniously revised the meaning of filiality, claiming a place for Christian filiality within orthodox boundaries of filial piety (xiao), while suggesting that Christianity offered a truer meaning of filiality, subordinated to the divine prerogatives of the Christian God.
Correlations between Hypothalamus-Pituitary-Adrenal Axis Parameters Depend on Age and Learning Capacity
Authors: Meijer O. C. , Topic B. , Steenbergen P. J. , Jocham G. , Huston J. P. , Oitzl M. S.
Published: November 2004

Glucocorticoid hormones are released after activation of the hypothalamus-pituitary-adrenal (HPA) axis and in the brain can modulate synaptic plasticity and memory formation. Clear individual differences in spatial learning and memory in the water maze allowed classification of groups of young (3 months) and aged (24 months) male Wistar rats as superior and inferior learners. We tested 1) whether measures of HPA activity are associated with cognitive functions and aging and 2) whether correlations of these measures depend on age and learning performance. Basal ACTH, but not corticosterone, was increased in aged rats, with the stress-induced ACTH response exaggerated in aged-inferior learners. Aged-superior learners had lower expression of glucocorticoid receptor and CRH mRNA in the parvocellular paraventricular nucleus of the hypothalamus compared with all other groups. Hippocampal mineralocorticoid receptor and glucocorticoid receptor mRNAs differed modestly between groups, but steroid receptor coactivator and heat-shock-protein 90 mRNAs were not different. Strikingly, correlations between HPA axis markers were dependent on grouping animals according to learning performance or age. CRH mRNA correlated with ACTH only in aged animals. Parvocellular arginine vasopressin mRNA was negatively correlated to basal corticosterone, except in aged-inferior learners. Corticosteroid receptor mRNA expression showed a number of correlations with other HPA axis regulators specifically in superior learners. In summary, the relationships between HPA axis markers differ for subgroups of animals. These distinct interdependencies may reflect adjusted set-points of the HPA axis, resulting in adaptation (or maladaptation) to the environment and, possibly, an age-independent determination of learning ability.
Chronic Treatment with the Monoamine Oxidase Inhibitor Phenelzine Increases Hypothalamic-Pituitary-Adrenocortical Activity in Male C57BL/6 Mice: Relevance to Atypical Depression
Authors: Kier Alison , Han Jie , Jacobson Lauren
Published: November 2004

Atypical depression has been linked to low hypothalamic-pituitary-adrenocortical axis activity and exhibits physical and affective symptoms resembling those of glucocorticoid deficiency. Because atypical depression has also been defined by preferential responsiveness to monoamine oxidase inhibitors (MAO-I), we hypothesized that MAO-I reverse these abnormalities by interfering with glucocorticoid feedback and increasing hypothalamic-pituitary-adrenocortical activity. To test this hypothesis, we measured plasma hormones and ACTH secretagogue gene expression in male C57BL/6 mice treated chronically with saline vehicle or phenelzine, a representative MAO-I. Changes in glucocorticoid feedback were evaluated using adrenalectomized (ADX) mice with and without corticosterone replacement. Antidepressant efficacy was confirmed by decreased immobility during forced swim testing. Phenelzine significantly increased circadian nadir and postrestraint plasma corticosterone levels in sham-operated mice, an effect that correlated with increased adrenocortical sensitivity to ACTH. Phenelzine increased circadian nadir, but not poststress ACTH in ADX mice, suggesting that phenelzine augmented corticosterone secretion in sham-operated mice by increasing stimulation and decreasing feedback inhibition of hypothalamic-pituitary activity. Consistent with the latter possibility, phenelzine significantly increased plasma ACTH and paraventricular hypothalamus CRH mRNA in ADX, corticosterone-replaced mice. Phenelzine did not increase paraventricular hypothalamus CRH or vasopressin mRNA in ADX mice lacking corticosterone replacement. We conclude that chronic phenelzine treatment induces sustained increases in glucocorticoids by impairing glucocorticoid feedback, increasing adrenocortical responsiveness to ACTH, and increasing glucocorticoid-independent stimulation of hypothalamic-pituitary activity. The resulting drive for adrenocortical activity could account for the ability of MAO-I to reverse endocrine and psychiatric symptoms of glucocorticoid deficiency in atypical depression.
Increased Neurogenesis in Dentate Gyrus of Long-Lived Ames Dwarf Mice
Authors: Sun Liou Y. , Evans M. Steven , Hsieh Jenny , Panici Jacob , Bartke Andrzej
Published: November 2004

Neurogenesis occurs throughout adult life in the dentate gyrus of mammalian hippocampus and has been suggested to play an important role in cognitive function. Multiple trophic factors including IGF-I have been demonstrated to regulate hippocampal neurogenesis. Ames dwarf mice live considerably longer than normal animals and maintain physiological function at youthful levels, including cognitive function, despite a deficiency of circulating GH and IGF-I. Here we show an increase in numbers of newly generated cells [bromodeoxyuridine (BrdU) positive] and newborn neurons (neuronal nuclear antigen and BrdU positive) in the dentate gyrus of adult dwarf mice compared with normal mice using BrdU labeling. Despite the profound suppression of hippocampal GH expression, hippocampal IGF-I protein levels are up-regulated and the corresponding mRNAs are as high in Ames dwarf as in normal mice. Our results suggest that local/hippocampal IGF-I expression may have induced the increase in hippocampal neurogenesis, and increased neurogenesis might contribute to the maintenance of youthful levels of cognitive function during aging in these long-lived animals.
The Putative Tumor Suppressor Deleted in Malignant Brain Tumors 1 Is an Estrogen-Regulated Gene in Rodent and Primate Endometrial Epithelium
Authors: Tynan Sharon , Pacia Emmanuel , Haynes-Johnson Donna , Lawrence Danielle , D’Andrea Michael R. , Guo Jian-Zhong , Lundeen Scott , Allan George
Published: November 2004

Deleted in malignant brain tumors 1 (DMBT1) is a candidate suppressor of malignancies of the brain, lung, gut, and breast. We have been studying gene expression in the uterus in the presence of estrogens and their antagonists. Here, we show that DMBT1 RNA levels are robustly increased by estrogen treatment in the uteri of ovariectomized monkeys and rats. In monkeys, the progestin antagonist mifepristone inhibits estrogen-dependent uterine proliferation. As determined by a microarray experiment and quantitative analysis of RNA levels, mifepristone inhibited estrogenic induction of DMBT1. DMBT1 was not expressed in intact monkeys that were treated with a gonadotropin agonist to suppress steroidogenesis. An in vitro transfection study with human DMBT1 promoter constructs showed that an Alu site approximately 3000 nucleotides upstream of the gene mediates estrogenic regulation. Surprisingly, the estrogen antagonists tamoxifen, raloxifene, and ICI 182,780 also induced gene expression via this Alu site. Rodents represent a more convenient model system for studying uterine biology than monkeys. In rats, uterine DMBT1 RNA levels were dramatically up-regulated by estrogen. Consistent with the transfection study, tamoxifen and raloxifene increased DMBT1 RNA levels in vivo, but ICI 182,780 inhibited an estrogen-induced increase. Immunohistochemical studies showed that DMBT1 is specifically induced in glandular and luminal epithelia of the rat endometrium. Our experiments establish that DMBT1 is an estrogen-responsive gene with a possible role in endometrial proliferation or differentiation, and they have implications for the putative tumor suppressive and mucosal protective functions of DMBT1 in the uterus.
Influence of the Outer Surface Layers of Crystals on the X-Ray Diffraction Intensity of Basal Reflections
Authors: Sakharov Boris A. , Plançon Alain , Lanson Bruno , Drits Victor A.
Published: November 2004

This study presents a mathematical formalism describing diffraction effects from periodic and mixed-layer minerals in which the outer surface layers of crystals possibly differ from layers forming the core of the crystals. The X-ray diffraction (XRD) patterns calculated for structure models of chlorite and irregular chlorite-smectites terminated on both sides of the crystals by either brucite-like sheets or 2:1 layers show the strong influence that different outer surface layers have on the distribution of basal reflection intensities. Simulation of the experimental XRD patterns from two chlorite samples having different Fe contents shows that in these two samples the chlorite crystals were terminated by brucite-like sheets on both sides. In contrast, crystals in a corrensite sample were terminated by water molecules and exchangeable cations. The nature of diffraction effects due to outer surface layers is discussed.