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It is generally accepted that carbon capture and storage strategies will play a crucial role for mitigating CO2emissions at short- and mid-term scenarios. In this study, a membrane gas absorption process was assessed as potential candidate method for CO2capture in a Greek brick production industry. The membrane contactor pilot unit was installed near the flue, where a slip stream of the flue gases was continuously sampled and fed in the hollow fiber membrane module. A 0.25 M aqueous diethanolamine solution was used as a typical solvent for CO2capture. The % CO2removal was chosen as a typical performance indicator and the liquid to gas flow ratio was chosen as the main controlling variable of the process. The test results indicate that almost complete CO2removal can be attained with a liquid to gas flow rate around 1, demonstrating the high potential of the proposed technology.

A hallmark of polycystic kidney diseases (PKDs) is aberrant proliferation, which leads to the formation and growth of renal cysts. Proliferation is mediated by cyclin-dependent kinases (Cdks), and the administration of roscovitine (a pan-Cdk inhibitor) attenuates renal cystic disease in juvenile cystic kidney (jck) mice. Cdk2is a key regulator of cell proliferation, but its specific role in PKD remains unknown. The aim of this study was to test the hypothesis that Cdk2deficiency reduces renal cyst growth in PKD. Three studies were undertaken: (i) a time course (days 28, 56, and 84) of cyclin and Cdk activity was examined in jckmice and compared with wild-type mice; (ii) the progression was compared in jckmice with or without Cdk2ablation from birth; and (iii) the effect of sirolimus (an antiproliferative agent) on Cdk2activity in jckmice was investigated. Renal disease in jckmice was characterized by diffuse tubular cyst growth, interstitial inflammation and fibrosis, and renal impairment, peaking on day 84. Renal cell proliferation peaked during earlier stages of disease (days 28–56), whereas the expression of Cdk2-cyclin partners (A and E) and Cdk1and 2activity, was maximal in the later stages of disease (days 56–84). Cdk2ablation did not attenuate renal disease progression and was associated with persistent Cdk1activity. In contrast, the postnatal treatment of jckmice with sirolimus reduced both Cdk2and Cdk1activity and reduced renal cyst growth. In conclusion, (i) the kinetics of Cdk2and Cdk2-cyclin partners did not correlate with proliferation in jckmice; and (ii) the absence of Cdk2did not alter renal cyst growth, most likely due to compensation by Cdk1. Taken together, these data suggest that Cdk2is dispensable for the proliferation of cystic epithelial cells and progression of PKD.

Nowadays, smartphones are regarded as an extension of individual selves, as they are used several times throughout the day. Lately, an increasing number of universities have adopted tailored smartphone applications to enhance students' engagement, performance and overall experience. Although early studies show that students accept this practice, they seem to shape their preferences and usage decisions based on the specific features that each application offers. The literature points towards some attributes that tend to influence mobile app users' decisions, such as personalisation and shareability. The current study aims to expand the findings of past research and explore the effect of application personalisation and shareability on higher education students' preferences. The results show that apps with personalisation and shareability features are preferred by students, who are also more eager to recommend the app to their peers and hold stronger in-app purchase intentions.

The organization of space and working time, especially their location and geography, is a significant concern to researchers and politicians. However, in today's globalized economy and online age, the way we work and the workplace's whole location and geography are being redefined and researched. This paper investigates the current situation of co-working spaces in Greece, and the authors further analyse the case study of the Athens municipality. They examined views on new workplaces satisfaction and the benefits of the location. The research also explored the factors influencing ‘co-working spaces' satisfaction and views on the location's benefits. Finally, there is a detailed record of the areas in question throughout the territory, and they are scattered and concentrated in certain areas. Their characteristics are then explored, and policies and actions are proposed for their operation and development in the post-COVID-19 era.

•Technical and environmental assessment of MEA and SPEI-based CO2capture technologies.•MEA requires 3.53 GJ/ton CO2, while SPEI requires 2.36 GJ/ton CO2regeneration energy.•SPEI-based process exhibits a 7 % lower global warming potential than MEA-based process.•SPEI has a 7 % lower impact on health, 9 % on ecosystems, and 26 % on resources than MEA.

Most of the drugs currently prescribed for cancer treatment are riddled with substantial side effects. In order to develop more effective and specific strategies to treat cancer, it is of importance to understand the biology of drug targets, particularly the newly emerging ones. A comprehensive evaluation of these targets will benefit drug development with increased likelihood for success in clinical trials. The folate-mediated one-carbon (1C) metabolism pathway has drawn renewed attention as it is often hyperactivated in cancer and inhibition of this pathway displays promise in developing anticancer treatment with fewer side effects. Here, we systematically review individual enzymes in the 1C pathway and their compartmentalization to mitochondria and cytosol. Based on these insight, we conclude that (1) except the known 1C targets (DHFR, GART, and TYMS), MTHFD2 emerges as good drug target, especially for treating hematopoietic cancers such as CLL, AML, and T-cell lymphoma; (2) SHMT2 and MTHFD1L are potential drug targets; and (3) MTHFD2L and ALDH1L2 should not be considered as drug targets. We highlight MTHFD2 as an excellent therapeutic target and SHMT2 as a complementary target based on structural/biochemical considerations and up-to-date inhibitor development, which underscores the perspectives of their therapeutic potential.

Progression through mitosis is balanced by the timely regulation of phosphorylation and dephosphorylation events ensuring the correct segregation of chromosomes before cytokinesis. This balance is regulated by the opposing actions of CDK1 and PP2A, as well as the Greatwall kinase/MASTL. MASTL is commonly overexpressed in cancer, which makes it a potential therapeutic anticancer target. Loss of Mastlinduces multiple chromosomal errors that lead to the accumulation of micronuclei and multilobulated cells in mitosis. Our analyses revealed that loss of Mastlleads to chromosome breaks and abnormalities impairing correct segregation. Phospho-proteomic data for Mastlknockout cells revealed alterations in proteins implicated in multiple processes during mitosis including double-strand DNA damage repair. In silico prediction of the kinases with affected activity unveiled NEK2 to be regulated in the absence of Mastl. We uncovered that, RAD51AP1, involved in regulation of homologous recombination, is phosphorylated by NEK2 and CDK1 but also efficiently dephosphorylated by PP2A/B55. Our results suggest that MastlKOdisturbs the equilibrium of the mitotic phosphoproteome that leads to the disruption of DNA damage repair and triggers an accumulation of chromosome breaks even in noncancerous cells.

In light of the accumulating evidence on the negative predictive value of soluble urokinase plasminogen activator receptor (suPAR), a group of experts from the fields of intensive care medicine, emergency medicine, internal medicine and infectious diseases frame a position statement on the role of suPAR in the screening of patients admitted to the emergency department. The statement is framed taking into consideration existing publications and our own research experience. The main content of this statement is that sUPAR is a non-specific marker associated with a high negative predictive value for unfavourable outcomes; levels < 4 ng/ml indicate that it is safe to discharge the patient, whereas levels > 6 ng/ml are an alarming sign of risk for unfavourable outcomes. However, the suPAR levels should always be interpreted in light of the patient's history.

A hallmark of polycystic kidney diseases (PKDs) is aberrant proliferation, which leads to the formation and growth of renal cysts. Proliferation is mediated by cyclin-dependent kinases (Cdks), and the administration of roscovitine (a pan-Cdk inhibitor) attenuates renal cystic disease in juvenile cystic kidney (jck) mice. Cdk2is a key regulator of cell proliferation, but its specific role in PKD remains unknown. The aim of this study was to test the hypothesis that Cdk2deficiency reduces renal cyst growth in PKD. Three studies were undertaken: (i) a time course (days 28, 56, and 84) of cyclin and Cdk activity was examined in jckmice and compared with wild-type mice; (ii) the progression was compared in jckmice with or without Cdk2ablation from birth; and (iii) the effect of sirolimus (an antiproliferative agent) on Cdk2activity in jckmice was investigated. Renal disease in jckmice was characterized by diffuse tubular cyst growth, interstitial inflammation and fibrosis, and renal impairment, peaking on day 84. Renal cell proliferation peaked during earlier stages of disease (days 28–56), whereas the expression of Cdk2-cyclin partners (A and E) and Cdk1and 2activity, was maximal in the later stages of disease (days 56–84). Cdk2ablation did not attenuate renal disease progression and was associated with persistent Cdk1activity. In contrast, the postnatal treatment of jckmice with sirolimus reduced both Cdk2and Cdk1activity and reduced renal cyst growth. In conclusion, (i) the kinetics of Cdk2and Cdk2-cyclin partners did not correlate with proliferation in jckmice; and (ii) the absence of Cdk2did not alter renal cyst growth, most likely due to compensation by Cdk1. Taken together, these data suggest that Cdk2is dispensable for the proliferation of cystic epithelial cells and progression of PKD.

Cell cycle regulation, especially faithful DNA replication and mitosis, are crucial to maintain genome stability. Cyclin-dependent kinase (CDK)/cyclin complexes drive most processes in cellular proliferation. In response to DNA damage, cell cycle surveillance mechanisms enable normal cells to arrest and undergo repair processes. Perturbations in genomic stability can lead to tumor development and suggest that cell cycle regulators could be effective targets in anticancer therapy. However, many clinical trials ended in failure due to off-target effects of the inhibitors used. Here, we investigate in vivo the importance of WEE1- and MYT1-dependent inhibitory phosphorylation of mammalian CDK1. We generated Cdk1AFknockin mice, in which two inhibitory phosphorylation sites are replaced by the non-phosphorylatable amino acids T14A/Y15F. We uncovered that monoallelic expression of CDK1AFis early embryonic lethal in mice and induces S phase arrest accompanied by γH2AX and DNA damage checkpoint activation in mouse embryonic fibroblasts (MEFs). The chromosomal fragmentation in Cdk1AFMEFs does not rely on CDK2 and is partly caused by premature activation of MUS81-SLX4 structure-specific endonuclease complexes, as well as untimely onset of chromosome condensation followed by nuclear lamina disassembly. We provide evidence that tumor development in liver expressing CDK1AFis inhibited. Interestingly, the regulatory mechanisms that impede cell proliferation in CDK1AFexpressing cells differ partially from the actions of the WEE1 inhibitor, MK-1775, with p53 expression determining the sensitivity of cells to the drug response. Thus, our work highlights the importance of improved therapeutic strategies for patients with various cancer types and may explain why some patients respond better to WEE1 inhibitors.

Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquetstage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit, Trf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment in Trf1-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to-end fusion due to the failure of recruiting meiosis specific telomere associated proteins. Further investigations uncovered that TRF1 could directly interact with Speedy A, and Speedy A might work as a scaffold protein to further recruit Cdk2, thus protecting telomeres from fusion at this stage. Together, our results reveal a novel mechanism of TRF1, Speedy A, and Cdk2 in protecting telomere from fusion in a highly crowded microenvironment during meiosis.

The purpose of this article is to investigate and model retail consumer purchase behavior and determine factors affecting the purchasing decision. The following hypotheses were verified: H1 tests the influence of “Decision-making Time” over “Final Purchase”. H2 tests “Promotion” over “Final Purchase”. H3, H4 and H5 were established to test the influence of demographic characteristics (respectively: Age, Nationality, Gender) over “Final Purchase”. SPSS 23 was used to analyze the collected data from the observations completed in the supermarket. In order to identify the explanatory power of the variables, a Logistic Regression model was developed. Empirical findings indicated that demographic characteristics (Age, Nationality, Gender), as well as “Time” and “Promotion,” have a significant effect on “Purchase” and that “Time” has a greater impact on “Purchase.” These results could be used to design marketing strategies in order to increase sales. However, a few limitations occurred during the study such as observation timing, the unicity of location and observers' subjectivity.

The meiotic functions of Emi2, an inhibitor of the APC/C complex, have been best characterized in oocytes where it mediates metaphase II arrest as a component of the cytostatic factor. We generated knockout mice to determine the in vivo functions of Emi2—in particular, its functions in the testis, where Emi2 is expressed at high levels. Male and female Emi2 knockout mice are viable but sterile, indicating that Emi2 is essential for meiosis but dispensable for embryonic development and mitotic cell divisions. We found that, besides regulating cell-cycle arrest in mouse eggs, Emi2 is essential for meiosis I progression in spermatocytes. In the absence of Emi2, spermatocytes arrest in early diplotene of prophase I. This arrest is associated with decreased Cdk1 activity and was partially rescued by a knockin mouse model of elevated Cdk1 activity. Additionally, we detected expression of Emi2 in spermatids and sperm, suggesting potential post-meiotic functions for Emi2.

ABSTRACTCyclin A2 is an essential gene for development and in haematopoietic stem cells and therefore its functions in definitive erythropoiesis have not been investigated. We have ablated cyclin A2 in committed erythroid progenitors in vivo using erythropoietin receptor promoter-driven Cre, which revealed its critical role in regulating erythrocyte morphology and numbers. Erythroid-specific cyclin A2 knockout mice are viable but displayed increased mean erythrocyte volume and reduced erythrocyte counts, as well as increased frequency of erythrocytes containing Howell-Jolly bodies. Erythroblasts lacking cyclin A2 displayed defective enucleation, resulting in reduced production of enucleated erythrocytes and increased frequencies of erythrocytes containing nuclear remnants. Deletion of the Cdk inhibitor p27Kip1but not Cdk2, ameliorated the erythroid defects resulting from deficiency of cyclin A2, confirming the critical role of cyclin A2/Cdk activity in erythroid development. Loss of cyclin A2 in bone marrow cells in semisolid culture prevented the formation of BFU-E but not CFU-E colonies, uncovering its essential role in BFU-E function. Our data unveils the critical functions of cyclin A2 in regulating mammalian erythropoiesis.

A unique feature of female germ cell development in mammals is their remarkably long arrest at the prophase of meiosis I, which lasts up to 50 years in humans. Both dormant and growing oocytes are arrested at prophase I and completely lack the ability to resume meiosis. Here, we show that the prolonged meiotic arrest of female germ cells is largely achieved via the inhibitory phosphorylation of Cdk1 (cyclin-dependent kinase 1). In two mouse models where we have introduced mutant Cdk1T14AY15Fwhich cannot be inhibited by phosphorylation (Cdk1AF) in small meiotically incompetent oocytes, the prophase I arrest is interrupted, leading to a premature loss of female germ cells. We show that in growing oocytes, Cdk1AF leads to premature resumption of meiosis with condensed chromosomes and germinal vesicle breakdown followed by oocyte death, whereas in dormant oocytes, Cdk1AF leads to oocyte death directly, and both situations damage the ovarian reserve that maintains the female reproductive lifespan, which should be around 1 year in mice. Furthermore, interruption of the inhibitory phosphorylation of Cdk1 results in DNA damage, which is accompanied by induction of the Chk2 (checkpoint kinase 2)-p53/p63-dependent cell death pathway, which eventually causes global oocyte death. Together, our data demonstrate that the phosphorylation-mediated suppression of Cdk1 activity is one of the crucial factors that maintain the lengthy prophase arrest in mammalian female germ cells, which is essential for preserving the germ cell pool and reproductive lifespan in female mammals.

Results of a study by Synchrotron X-ray Topography in transmission of the perfection of vapour grown single crystals of mercuric iodide, α-HgI2, in regions containing striations are presented. The geometry of the striations was precisely defined because we could examine several samples cut along different orientations ; moreover topographs recorded at different stages of crystal thinning allowed us to have an insight of the long range strain field associated with the striations and to resolve the defects inside them. A possible origin of these defects is discussed.

Material weaknesses in the internal control system of a company create more opportunities for managers to engage in opportunistic earnings management. In this study the authors investigate the relation between earnings management and disclosed material weaknesses in the internal controls, both under SOX 302 and SOX 404, and examine whether audit quality, measured as being audited by a Big Four auditor, has an effect on that relation. The results suggest that material weakness firms have more absolute discretionary accruals and greater income-decreasing discretionary accruals. So evidence is provided that material weakness firms engage in more earnings management, however not in opportunistic income-increasing earnings management. When audit quality is high, measured as being audited by a Big Four auditor, the disclosed material weaknesses are lower just as total and absolute discretionary accruals are. It is also interesting in our findings that when material weakness firms are audited by a Big Four auditor a positive relationship seems to exist with discretionary accruals, suggesting that when a firm is audited by a Big Four auditor, material weaknesses in the internal controls will lead to opportunistic earnings management.

A comparative study of two Greek cities, Chania and Kalamata, has been conducted regarding their creative potential. The cities are similar in many ways, i.e. regarding climate, goods produced, dependence on tourism etc, yet their cultural capital has been created through different patterns, and also identity formation of local societies has been built on different foundations. Cultural policies of the municipalities have also been oriented to different goals. Municipality of Kalamata has launched an all-encompassing cultural campaign, having dance as its spearhead. On the other hand, municipality of Chania, while offering an integrated cultural program in summer, it focuses more on letters and local history. Since promotion of arts has been hindered due to austerity measures, municipalities had to re-orient their strategy according to the new unfavorable developments. Despite their rich cultural capital, it is questionable whether these cities could be designated as “creative” according to Florida’s criteria, mainly because of the tight bonding ties of local societies.

During neurogenesis, cell cycle regulators play a pivotal role in ensuring proper proliferation, cell cycle exit, and differentiation of neural precursors. However, the precise role of cyclin‐dependent kinases (Cdks) in these processes is not well understood. We generated Cdk2 and Cdk4 double knockout (DKO) mice and found a striking ablation of the intermediate zone and cortical plate in mouse embryonic brain. When neural stem cells (NSCs) were isolated and analyzed, DKO NSCs proliferated comparable to wild type as Cdk1 now binds to cyclin D1 and E1 and assumes the role vacated by the loss of Cdk2 and Cdk4 in phosphorylating Rb. Although compensation was sufficient for the maintenance of self‐renewal and multilineage potential, DKO NSCs displayed an altered cell cycle profile and were more prone to neuronal differentiation. This was manifested in vivo as a marked reduction in S‐phase length and an increased tendency for neurogenic divisions that prevented proper expansion of the basal progenitor pool. Our data thus demonstrate the induction of neurogenic divisions in the absence of critical mediators of G1/S transition—Cdk2 and Cdk4, and highlight their evolutionary importance in the determination of cortical thickness. STEMCells2012;30:1509–1520

Plant growth and crop production can be greatly affected by common environmental stresses such as drought, high salinity and low temperatures. Gene expression is affected by several abiotic stresses. Stress-inducible genes are regulated by transcription factors and epigenetic mechanisms such as histone modifications. In this Mini-Review, we have explored the role of transcriptional adaptor ADA2b in Arabidopsis responses to abiotic stress. ADA2b is required for the expression of genes involved in abiotic stress either by controlling H3 and H4 acetylation in the case of salt stress or affecting nucleosome occupancy in low temperatures response.

Cdk2 was once believed to play an essential role in cell cycle progression, but cdk2-/- mice have minimal phenotypic abnormalities. In this study, we examined the role of cdk2 in hepatocyte proliferation, centrosome duplication, and survival. Cdk2-/- hepatocytes underwent mitosis and had normal centrosome content after mitogen stimulation. Unlike wild-type cells, cdk2-/- liver cells failed to undergo centrosome overduplication in response to ectopic cyclin D1 expression. After mitogen stimulation in culture or partial hepatectomy in vivo, cdk2-/- hepatocytes demonstrated diminished proliferation. Cyclin D1 is a key mediator of cell cycle progression in hepatocytes, and transient expression of this protein is sufficient to promote robust proliferation of these cells in vivo. In cdk2-/- mice and animals treated with the cdk2 inhibitor seliciclib, cyclin D1 failed to induce hepatocyte cell cycle progression. Surprisingly, cdk2 ablation or inhibition led to massive hepatocyte and animal death following cyclin D1 transfection. In a transgenic model of chronic hepatic cyclin D1 expression, seliciclib induced hepatocyte injury and animal death, suggesting that cdk2 is required for survival of cyclin D1-expressing cells even in the absence of substantial proliferation. In conclusion, our studies demonstrate that cdk2 plays a role in liver regeneration. Furthermore, it is essential for centrosome overduplication, proliferation, and survival of hepatocytes that aberrantly express cyclin D1 in vivo. These studies suggest that cdk2 may warrant further investigation as a target for therapy of liver tumors with constitutive cyclin D1 expression.

The protonation of [Co2(CO)6{9‐[(allyldimethylsilyl)ethynyl]‐9H‐fluoren‐9‐ol}] (4), with HBF4in CH2Cl2led to migration of the allyl group from silicon to the cobalt‐stabilised cationic site to furnish [Co2(CO)6{9‐allyl‐9‐[(dimethylfluorosilyl)ethynyl]‐9H‐fluorene}] (17). However, under the same conditions, [Co2(CO)6{9‐[(benzyldimethylsilyl)ethynyl]‐9H‐fluoren‐9‐ol}] (5) underwent desilylation and rearrangement of the resulting terminal alkyne–dicobalt complex to give [Co3(CO)9(9H‐fluorenylmethylcarbynyl)] (24); moreover, dimerisation of the (benzyldimethylsilyl)ethynyl‐9H‐fluorenyl moiety led to the propargyl–allene 26. In contrast, protonation of 5in THF yielded [{Co2(CO)6{[(benzyldimethylsilyl)ethynyl‐9H‐fluorenyl])}2peroxide] (27) through a radical coupling process. Analogously, protonation of [Co2(CO)6{9‐[(vinyldimethylsilyl)ethynyl]‐9H‐fluoren‐9‐ol}] (6) yields the corresponding peroxide 28. X‐ray crystallographic data are reported for, among others, complexes 17, 24, 26, 27and 28.

Abstract: This paper places certain religious ideas of Eastern Christianity about our relationship to nature critically against techno-scientific thinking and practice. Specifically, the two focal issues of the discussion are the concept of religious sin, on the one hand, and the peculiarly modern fusion of science and technology, resulting in the novel phenomenon of techno-science, on the other. Two corresponding theses are advanced: that of sin as an epistemic, and not as a moral, error, and that of the “Eucharistic” viz., celebratory relation with God. The paper then proceeds to trace significant parallels that may be discerned between the Orthodox theological view and Heidegger’s position on technology, and metaphysics more generally, culminating in the suggestion that the way out of the ‘danger’ of technology as techno-science must be found in art or religion.

Cdk1 was proposed to compensate for the loss of Cdk2. Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint. Cdk2–/–mouse embryonic fibroblasts in vitro as well as regenerating liver cells after partial hepatectomy (PH) in Cdk2–/–mice, arrest promptly at the G1/S checkpoint in response to γ-irradiation due to activation of p53 and p21 inhibiting Cdk1. Furthermore re-entry into S phase after irradiation was delayed in Cdk2–/–cells due to prolonged and impaired DNA repair activity. In addition, Cdk2–/–mice were more sensitive to lethal irradiation compared to wild-type and displayed delayed resumption of DNA replication in regenerating liver cells. Our results suggest that the G1/S DNA damage checkpoint is intact in the absence of Cdk2, but Cdk2 is important for proper repair of the damaged DNA.

Cdk1 was proposed to compensate for the loss of Cdk2. Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint. Cdk2−/−mouse embryonic fibroblasts in vitro as well as regenerating liver cells after partial hepatectomy (PH) in Cdk2−/−mice, arrest promptly at the G1/S checkpoint in response to γ-irradiation due to activation of p53 and p21 inhibiting Cdk1. Furthermore re-entry into S phase after irradiation was delayed in Cdk2−/−cells due to prolonged and impaired DNA repair activity. In addition, Cdk2−/−mice were more sensitive to lethal irradiation compared to wild-type and displayed delayed resumption of DNA replication in regenerating liver cells. Our results suggest that the G1/S DNA damage checkpoint is intact in the absence of Cdk2, but Cdk2 is important for proper repair of the damaged DNA.

Advances in information and communications technologies (ICTs) have strategic implications for a wide range of industries. Tourism and hospitality have been dramatically changed by the ICTs and the Internet and have gradually emerged as the leading industry in online expenditure. The Internet revolutionized traditional distribution models, enabled new entries, propelled both disintermediation and reintermediation and altered the sources of competitive advantage. This paper explores the strategic implications of ICTs and the perceived advantages and disadvantages of Internet distribution for small and medium-sized hospitality enterprises (SMEs). Primary research in Athens' hotels demonstrates the effects of the Internet and ICTs for secondary markets, where there is lower penetration and ICT adoption. Interviews and questionnaires identified a number of strategies in order to optimize distribution. The analysis illustrates the strategic role of ICTs and the Internet for hospitality organizations and small and medium-sized organizations in general. Most hotels employ a distribution mix that determines the level and employment of the Internet. The paper demonstrates that only organizations that use ICTs strategically will be able to develop their electronic distribution and achieve competitive advantages in the future.

Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell-cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of S-phase entry. We used Cdk2-deficient mice to decipher the requirement of Cdk2 for the generation of new neurons in the adult hippocampus. The quantification of cell cycle markers first revealed that the lack of Cdk2 activity does not influence spontaneous or seizure-induced proliferation of neural progenitor cells (NPC) in the adult DG. Using bromodeoxyuridine incorporation assays, we showed that the number of mature newborn granule neurons generated de novo was similar in both wild-type (WT) and Cdk2-deficient adult mice. Moreover, the apparent lack of cell output reduction in Cdk2-/- mice DG did not result from a reduction in apoptosis of newborn granule cells as analyzed by TUNEL assays. Our results therefore suggest that Cdk2 is dispensable for NPC proliferation, differentiation and survival of adult-born DG granule neurons in vivo. These data emphasize that functional redundancies between Cdks also occur in the adult brain at the level of neural progenitor cell cycle regulation during hippocampal neurogenesis.

PvLHYand Lhcbexpression has been studied in primary bean leaves after exposure of etiolated leaves to two or three white light-pulses and under different photoperiods. Under the tested photoperiods, the steady-state mRNA levels exhibit diurnal oscillations with zenith in the morning between ZT21 and 4 for PvLHYand between ZT4 and 6 for Lhcb. Nadir is in the evening between ZT12 and 18 for PvLHYand ZT18 and 24 for Lhcb. Light-pulses to etiolated seedlings induce a differentiated acute response that is reciprocally correlated with the amplitude of the following circadian cycle. In addition, the clock modulates the duration of the acute response (descending part of the curve included), which according to the phase of the rhythm at light application extends from 7 to 18 h. This constitutes the response dynamics of the Phaseolusclock to light. Similarly, the waveform of PvLHYand Lhcbexpression during the day of different photoperiods resembles in induction capability (accomplishment of peak after lights-on) and duration (from lights-on phase to trough) the phase-dependent progression of acute response in etiolated seedlings. Consequently, the peak of Lhcb(all tested photoperiods) and PvLHY(in LD 18:6) attained in the photophase corresponds to the acute response peak, while the peak of PvLHYduring the scotophase (in LD 12:12 and 6:18) corresponds to the circadian peak. Thus, the effect of the response dynamics in the photoperiod determines the coincidence of the peak with the photo- or scotophase, respectively. This represents a new model mechanism for the adaptation of the Phaseolusclock to light.PvLHYand Lhcbexpression has been studied in primary bean leaves after exposure of etiolated leaves to two or three white light-pulses and under different photoperiods. Under the tested photoperiods, the steady-state mRNA levels exhibit diurnal oscillations with zenith in the morning between ZT21 and 4 for PvLHYand between ZT4 and 6 for Lhcb. Nadir is in the evening between ZT12 and 18 for PvLHYand ZT18 and 24 for Lhcb. Light-pulses to etiolated seedlings induce a differentiated acute response that is reciprocally correlated with the amplitude of the following circadian cycle. In addition, the clock modulates the duration of the acute response (descending part of the curve included), which according to the phase of the rhythm at light application extends from 7 to 18 h. This constitutes the response dynamics of the Phaseolusclock to light. Similarly, the waveform of PvLHYand Lhcbexpression during the day of different photoperiods resembles in induction capability (accomplishment of peak after lights-on) and duration (from lights-on phase to trough) the phase-dependent progression of acute response in etiolated seedlings. Consequently, the peak of Lhcb(all tested photoperiods) and PvLHY(in LD 18:6) attained in the photophase corresponds to the acute response peak, while the peak of PvLHYduring the scotophase (in LD 12:12 and 6:18) corresponds to the circadian peak. Thus, the effect of the response dynamics in the photoperiod determines the coincidence of the peak with the photo- or scotophase, respectively. This represents a new model mechanism for the adaptation of the Phaseolusclock to light.

Depending upon the cellular and physiologic context, the overexpression of the MYC proto-oncogene results in rapid cell growth, proliferation and/or induction of apoptosis. What determines the precise consequences upon MYC activation is not clear. We have found that cyclin-dependent kinase 2 (CDK2) is required by MYC to induce apoptosis. MYC-induced apoptosis was suppressed in mouse embryonic fibroblasts (MEF) knocked out for Cdk2 or normal human fibroblasts (NHF) upon expression of the CDK2 inhibitor p27 or treated with RNAi directed at CDK2. Knockout of Cdk2 did not prevent MYC from inducing p53 and Bim. The inhibition of CDK2 did not prevent apoptosis induced by the DNA damaging agent etoposide. Our results surprisingly suggest that CDK2 defines whether MYC induction causes apoptosis.

It has been long believed that the cyclin-dependent kinase 2 [Cdk2] binds to cyclin E or cyclin Aand exclusively promotes the G1/S phase transition and that Cdc2/cyclin B complexes play a majorrole in mitosis. We now provide evidence that Cdc2 binds to cyclin E [in addition to cyclin A & B]and is able to promote the G1/S transition. This new concept indicates that both Cdk2 and/or Cdc2can drive cells through G1/S phase in parallel. In this review we discuss the classic cell cycle modeland how results from knockout mice provide new evidence that refute this model. We focus on newroles of Cdc2 and p27 in regulating the mammalian cell cycle and propose a new model for cellcycle regulation that accommodates these novel findings.

Abstract Is a Health Care Ethics possible? Against sceptical and relativist doubts Kantian deontology may advance a challenging alternative affirming the possibility of such an ethics on the condition that deontology be adopted as a total programme or complete vision. Kantian deontology is enlisted to move us from an ethics of two-person informal care to one of institutions. It justifies this affirmative answer by occupying a commanding meta-ethical stand. Such a total programme comprises, on the one hand, a dual-aspect strategy incorporating the macro- (institutional) and micro- (person-to-person) levels while, on the other, it integrates consistently within moral epistemology a meta-ethics with lower-ground moral theories. The article describes the issues to be dealt with and the problems which have to be solved on the way to a unifying theory of that kind (Sections I-III) and indicates elements of Kantian moral philosophy which may serve as building blocks (Section IV). Among these are not only Kant’s ideas concerning the moral acting of persons and his ideas concerning civil society and state but also his ideas concerning morality, schematism and religion.

Kaposi sarcoma–associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kCYC mRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYC mRNA by in situ hybridization. In summary, kCYC expression within VEGFR-3+ cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors.

Kaposi sarcoma–associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin(kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYCunder the control of the VEGFR-3 promoter. kCYCmRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYCmRNA by in situ hybridization. In summary, kCYCexpression within VEGFR-3+cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors.

In this essay, I will argue that there is a formal contradiction at the heart of The Personals: the intensely serious content and austere presentation of Du’s private life stand in striking opposition to the comical content and playful presentation of her interviews with prospective suitors. Following this, I explore the desires underlying this contradiction, and contextualized the film’s representational strategies and within contemporary discourses of gender and sexuality. I follow this with a brief discussion of the film’s generic qualities, namely resonances between The Personals and some similarly-structured Taiwan films of recent years. Finally, I conclude with information on the film’s marketing strategy and international circulation.

This paper presents aphilosophical approach to the semiotics of lawin terms of an exercise in symbolictransposition whereby aesthetic categories arebrought to bear on jurisprudence, and inparticular on two of its foundationalquestions. These questions, the backdropagainst which the analysis unfolds, ask (1)whether law is static or dynamic; and (2)whether law `constitutes' human beings, in somespecific sense, or whether the reverse holds. The notions of universality and necessity andthat of utopia are employed together with twoopposite art symbols and a model of theirantitheses is constructed revealing diverseanswers as to how to conceive law in relationto the two questions. One answer is singled outby adopting the principles of Kantian aesthetic(reflective) judgement: to elicit an aestheticclaim, law must be seen as a utopian socialorder exhibiting purposiveness without,however, presupposing any predeterminedsubstantive normative end. This is effected bya special reading permitting the combination ofnecessitation (obligation) with free play – thisbeing the common ground shared by both law andaesthetics but only in this limiting utopianmoment. This is a unique sense in which legaldiscourse is formally assimilated to aestheticnon-purposive judgements yet withoutrelinquishing law's distinctive feature aspurposive order prescribing, however,prescription alone as a formal end.

This work reports the CO2 plasticization of gas‐separation hollow‐fiber membranes based on polyimide and polyethersulfone blends. The feed pressure effect on the permeance of pure gases (CO2, N2) and the separation performance of a gaseous mixture (CO2/N2, 55/45%) is examined. Contrary to dense membranes, the permeance of CO2 through ultrathin asymmetric fibers increases immediately with pressure resulting in pronounced apparent plasticization and reduction of the ideal CO2/N2 selectivity. However, no evidence of plasticization was observed when a CO2/N2, 55/45% mixture was fed to the hollow‐fiber membranes. In all cases, CO2 permeance decreased with pressure, while that of N2 remained constant. Experimental results were validated by means of mathematical modeling. Membrane‐separation performance was overestimated when pressure‐independent permeabilities were used in the model, while pressure‐dependent permeabilities, due to the overall effect of plasticization and competition phenomena, explained excellently, the obtained stage‐cut and permeate purity.

In order to understand some aspects of the circadian clock function in Phaseolus vulgaris, we analyzed the temporal transcript profile of Lhcbgenes, typical clock reporters in plants, and that of PvLHY, an orthologue of Arabidopsis thaliana LHYwhich is a putative transcription factor of Lhcbgenes. Under different light regimes, Lhcband PvLHYexhibit a clear circadian pattern of expression. Moreover, the rhythm of Lhcbgenes appears to be tightly coupled to that of PvLHYwith the latter having a slightly earlier phase. This supports the idea that the oscillating capacity of PvLHYmay be one of the causes of the rhythmic expression of Lhcbgenes in bean. In addition to their circadian regulation, Lhcband PvLHYare induced by light with similar and relatively slow induction kinetics. Moreover, this light induction is gated by the circadian oscillator: minimal responses occur at times around peaks of the pre-existing rhythm, while maximal ones occur at troughs of the pre-existing rhythm. This pattern of gating is opposite to that observed in Arabidopsis. The failure to block the light induction pathways at pre-existing troughs appears to have a detrimental effect to the subsequent circadian rhythmicity. Briefly, the overall regulation of PvLHYand Lhcbgenes by light and the circadian clock reveals different strategies between Phaseolusand Arabidopsisin the adaptation to photoperiodic conditions.

Upon protonation with HBF4, [2-endo-((allyldimethylsilyl)ethynyl)borneol]Co2(CO)6 (2) suffers elimination of water or propene, to yield [2-((allyldimethylsilyl)ethynyl)born-2-ene]Co2(CO)6 (11) and [2-endo-((dimethylfluorosilyl)ethynyl)borneol]Co2(CO)6 (12), respectively, and, surprisingly, the tricobalt complex (2-norbornylidene)CHCCo3(CO)9 (13). In contrast, protonation of the terminal alkyne (2-endo-ethynylborneol)Co2(CO)6 (19), an anticipated precursor to 13, led instead to (2-ethynyl-2-bornene)Co2(CO)6 (21) and the ring-opened species (2-ethynyl-4-isopropyl-1-methylcyclohexa-1,3-diene)Co2(CO)6 (22). However, conversion of 19 to 13 was achievable upon prolonged heating at reflux in acetone, thereby also affording the corresponding alcohol [2-(2-hydroxybornyl)]CH2CCo3(CO)9 (20). A mechanistic rationale is offered for the formation of RCH2CCo3(CO)9 clusters upon protonation of alkyne complexes of the type (RC&tbd1;CH)Co2(CO)6.

Mild thermolysis of a toluene solution of [(η5-C₅H₅)Mo(CO)₃(C&z.tbd;CPh)] and [Fe₃(CO)₉(μ₃-E)₂] (E = S, Se) resulted in the formation of mixed-metal clusters, [(η5-C₅H₅)₂Mo₂Fe₃(CO)₈(μ₃-E)₂{μ₅-CC(Ph)CC(Ph)}] (E = S, 1; Se, 2), [(η5-C₅H₅)₂Mo₂Fe₄(CO)₉(μ₃-E)₂(μ₄-CCPh)₂] (E = S, 3; Se, 4) and [(η5-C₅H₅)₂Mo₂Fe₃(CO)₇(μ₃-E)₂{μ₅-CC(Ph)C(Ph)C}] (E = S 5; E = Se 6) which feature head-to-tail coupling of two acetylide groups, two acetylide groups which remain uncoupled and a tail-to-tail coupling of two acetylide groups, respectively, on the chalcogen-bridged Fe/Mo cluster framework. Under similar conditions, the reaction of [(η5-C₅H₅)W(CO)₃(C&z.tbd;CPh)] and [Fe₃(CO)₉(μ₃-E)₂] formed the clusters [(η5-C₅H₅)₂W₂Fe₃(CO)₇(μ₃-E)₂(μ₃-η2-CCPh)(μ₃-η1-CCH₂Ph)] (E = S, 7 or Se, 8) and [(η5-C₅H₅)WFe₂(CO)₈(μ-CCPh)] (9). All compounds have been characterised by IR and 1H and 13C NMR spectroscopy. The Se-bridged compounds have been further characterised by 77Se NMR spectroscopy. The crystal structures of 1, 3 and 5–9 were elucidated by X-ray diffraction methods.

CAK1 encodes a protein kinase in Saccharomyces cerevisiae whose sole essential mitotic role is to activate the Cdc28p cyclin-dependent kinase by phosphorylation of threonine-169 in its activation loop. SMK1 encodes a sporulation-specific mitogen-activated protein (MAP) kinase homolog that is required to regulate the postmeiotic events of spore wall assembly. CAK1 was previously identified as a multicopy suppressor of a weakened smk1 mutant and shown to be required for spore wall assembly. Here we show that Smk1p, like other MAP kinases, is phosphorylated in its activation loop and that Smk1p is not activated in a cak1 missense mutant. Strains harboring a hyperactivated allele of CDC28 that is CAK1 independent and that lacks threonine-169 still require CAK1 to activate Smk1p. The data indicate that Cak1p functions upstream of Smk1p by activating a protein kinase other than Cdc28p. We also found that mutants lacking CAK1 are blocked early in meiotic development, as they show substantial delays in premeiotic DNA synthesis and defects in the expression of sporulation-specific genes, including IME1. The early meiotic role of Cak1p, like the postmeiotic role in the Smk1p pathway, is CDC28 independent. The data indicate that Cak1p activates multiple steps in meiotic development through multiple protein kinase targets.

ABSTRACTCAK1encodes a protein kinase in Saccharomyces cerevisiaewhose sole essential mitotic role is to activate the Cdc28p cyclin-dependent kinase by phosphorylation of threonine-169 in its activation loop. SMK1encodes a sporulation-specific mitogen-activated protein (MAP) kinase homolog that is required to regulate the postmeiotic events of spore wall assembly. CAK1was previously identified as a multicopy suppressor of a weakened smk1mutant and shown to be required for spore wall assembly. Here we show that Smk1p, like other MAP kinases, is phosphorylated in its activation loop and that Smk1p is not activated in a cak1missense mutant. Strains harboring a hyperactivated allele of CDC28that is CAK1independent and that lacks threonine-169 still require CAK1to activate Smk1p. The data indicate that Cak1p functions upstream of Smk1p by activating a protein kinase other than Cdc28p. We also found that mutants lacking CAK1are blocked early in meiotic development, as they show substantial delays in premeiotic DNA synthesis and defects in the expression of sporulation-specific genes, including IME1. The early meiotic role of Cak1p, like the postmeiotic role in the Smk1p pathway, is CDC28independent. The data indicate that Cak1p activates multiple steps in meiotic development through multiple protein kinase targets.

CAK1encodes a protein kinase in Saccharomyces cerevisiaewhose sole essential mitotic role is to activate the Cdc28p cyclin-dependent kinase by phosphorylation of threonine-169 in its activation loop. SMK1encodes a sporulation-specific mitogen-activated protein (MAP) kinase homolog that is required to regulate the postmeiotic events of spore wall assembly. CAK1was previously identified as a multicopy suppressor of a weakened smk1mutant and shown to be required for spore wall assembly. Here we show that Smk1p, like other MAP kinases, is phosphorylated in its activation loop and that Smk1p is not activated in a cak1missense mutant. Strains harboring a hyperactivated allele of CDC28that is CAK1independent and that lacks threonine-169 still require CAK1to activate Smk1p. The data indicate that Cak1p functions upstream of Smk1p by activating a protein kinase other than Cdc28p. We also found that mutants lacking CAK1are blocked early in meiotic development, as they show substantial delays in premeiotic DNA synthesis and defects in the expression of sporulation-specific genes, including IME1. The early meiotic role of Cak1p, like the postmeiotic role in the Smk1p pathway, is CDC28independent. The data indicate that Cak1p activates multiple steps in meiotic development through multiple protein kinase targets.

In normal cells, activation of cyclin-dependent kinases (cdks) requires binding to a cyclin and phosphorylation by the cdk-activating kinase (CAK). The Kaposi's sarcoma-associated herpesvirus encodes a protein with similarity to D-type cyclins. This KSHV-cyclin activates CDK6, alters its substrate specificity, and renders CDK6 insensitive to inhibition by the cdk inhibitor p16INK4a. Here we investigate the regulation of the CDK6/KSHV-cyclin kinase with the use of purified proteins and a cell-based assay. We find that KSHV-cyclin can activate CDK6 independent of phosphorylation by CAK in vitro. In addition, CAK phosphorylation decreased the p16INK4asensitivity of CDK6/KSHV-cyclin complexes. In cells, expression of CDK6 or to a lesser degree of a nonphosphorylatable CDK6T177Atogether with KSHV-cyclin induced apoptosis, indicating that CDK6 activation by KSHV-cyclin can proceed in the absence of phosphorylation by CAK in vivo. Coexpression of p16 partially protected cells from cell death. p16 and KSHV-cyclin can form a ternary complex with CDK6 that can be detected by binding assays as well as by conformational changes in CDK6. The Kaposi's sarcoma-associated herpesvirus has adopted a clever strategy to render cell cycle progression independent of mitogenic signals, cdk inhibition, or phosphorylation by CAK.

In normal cells, activation of cyclin-dependent kinases (cdks) requires binding to a cyclin and phosphorylation by the cdk-activating kinase (CAK). The Kaposi's sarcoma-associated herpesvirus encodes a protein with similarity to D-type cyclins. This KSHV-cyclin activates CDK6, alters its substrate specificity, and renders CDK6 insensitive to inhibition by the cdk inhibitor p16(INK4a). Here we investigate the regulation of the CDK6/KSHV-cyclin kinase with the use of purified proteins and a cell-based assay. We find that KSHV-cyclin can activate CDK6 independent of phosphorylation by CAK in vitro. In addition, CAK phosphorylation decreased the p16(INK4a) sensitivity of CDK6/KSHV-cyclin complexes. In cells, expression of CDK6 or to a lesser degree of a nonphosphorylatable CDK6(T177A) together with KSHV-cyclin induced apoptosis, indicating that CDK6 activation by KSHV-cyclin can proceed in the absence of phosphorylation by CAK in vivo. Coexpression of p16 partially protected cells from cell death. p16 and KSHV-cyclin can form a ternary complex with CDK6 that can be detected by binding assays as well as by conformational changes in CDK6. The Kaposi's sarcoma-associated herpesvirus has adopted a clever strategy to render cell cycle progression independent of mitogenic signals, cdk inhibition, or phosphorylation by CAK.

The anharmonic behavior of the Raman-active oxygen modes was examined in YBa2Cu3^16,18Ox compounds over the whole range of oxygen doping (6 &lt; x &lt; 7). The apex phonon of Ag symmetry shows a small anharmonicity in the range of 6.4 &lt; x &lt; 6.9, which can be attributed to the anharmonic behavior of this mode in one of the constituent phases (ortho-II, ortho-III, etc.), but not in the ortho-I phase. The B1g mode does not show any anharmonicity over the whole range of oxygen doping, but characteristic spectral changes appear for x ≈ 6.3 and 6.7. At the lowest oxygen content studied (x = 6.03), there is a considerable amount of anharmonicity for the in-phase phonon of the plane oxygen atoms, which remains large until x ≈ 6.3, at the phase transition to the tetragonal phase, where it drops to zero. It increases again for x ≈ 6.4 and then gradually decreases with doping to disappear at the optimal doping. If these changes are combined with the spectral modifications of the B1g and in-phase modes, they indicate that local structural changes are induced by the transfer of carriers to the CuO2 planes at x ≈ 6.3, which are related to the reduction in anharmonicity, the pinning of the carriers and superconductivity. Copyright © 2001 John Wiley & Sons, Ltd.

We previously reported that the activating phosphorylation on cyclin-dependent kinases in yeast (Cdc28p) and in humans (Cdk2) is removed by type 2C protein phosphatases. In this study, we characterize this PP2C-like activity in HeLa cell extract and determine that it is due to PP2Cβ2, a novel PP2Cβ isoform, and to PP2Cα. PP2Cα and PP2Cβ2 co-purified with Mg2+-dependent Cdk2/Cdk6 phosphatase activity in DEAE-Sepharose, Superdex-200, and Mono Q chromatographies. Moreover, purified recombinant PP2Cα and PP2Cβ2 proteins efficiently dephosphorylated monomeric Cdk2/Cdk6 in vitro. The dephosphorylation of Cdk2 and Cdk6 by PP2C isoforms was inhibited by the binding of cyclins. We found that the PP2C-like activity in HeLa cell extract, partially purified HeLa PP2Cα and PP2Cβ2 isoforms, and the recombinant PP2Cs exhibited a comparable substrate preference for a phosphothreonine containing substrate, consistent with the conservation of threonine residues at the site of activating phosphorylation in CDKs.