944 resultados para Delay in Diagnosis


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In this work, we proposes a control strategy that allows the remote manipulator follow the local manipulator through the state convergence even if it has a delay in the communication channel. The bilateral control of the teleoperator system considers the case were the human operator applies a constant force on the local manipulator and when the interaction of the remote manipulator with the environment is considered passive. The stability analysis was performed using Lyapunov- Krasovskii functional, it showed for the case with constant delay, that using a proposed control algorithm by state convergence resulted in asymptotically stable, local and remote the nonlinear teleoperation system.

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Cuando la separación física entre el sistema local y remoto es relativamente corta, el retardo no es perceptible; sin embargo, cuando el manipulador local y el manipulador remoto se encuentran a una distancia lejana uno del otro, el retardo de tiempo ya no es insignificante e influye negativamente en la realización de la tarea. El retardo de tiempo en un sistema de control introduce un atraso de fase que a su vez degrada el rendimiento del sistema y puede causar inestabilidad. Los sistemas de teleoperación pueden sacar provecho de la posibilidad de estar presente en dos lugares simultáneamente, sin embargo, el uso de Internet y otras redes de conmutación de paquetes, tales como Internet2, impone retardos de tiempo variables, haciendo que los esquemas de control ya establecidos elaboren soluciones para hacer frente a inestabilidades causadas por estos retardos de tiempo variables. En este trabajo de tesis se presenta el modelado y análisis de un sistema de teloperación bilateral no lineal de n grados de libertad controlado por convergencia de estado. La comunicación entre el sitio local y remoto se realiza mediante un canal de comunicación con retardo de tiempo. El análisis presentado en este trabajo considera que el retardo puede ser constante o variable. Los principales objetivos de este trabajo son; 1) Desarrollar una arquitectura de control no lineal garantizando la estabilidad del sistema teleoperado, 2) Evaluar la estabilidad del sistema considerando el retardo en la comunicación, y 3) Implementación de los algoritmos desarrollados para probar el desempeño de los mismos en un sistema experimental de 3 grados de libertad. A través de la teoría de Estabilidad de Lyapunov y el funcional Lyapunov-Krasovskii, se demuestra que el sistema de lazo cerrado es asintóticamente estable. Estas conclusiones de estabilidad se han obtenido mediante la integración de la función de Lyapunov y aplicando el Lema de Barbalat. Se demuestra también que se logra sincronizar las posiciones del manipulador local y remoto cuando el operador humano no mueve el manipulador local y el manipulador remoto se mueve libremente. El esquema de control propuesto se ha validado mediante simulación y en forma experimental empleando un sistema de teleoperación real desarrollado en esta tesis doctoral y que consta de un un manipulador serie planar de tres grados de libertad, un manipulador local, PHANTOM Omni, el cual es un dispositivo haptico fabricado que consta de 3 grados de libertad (en fuerza) y que proporciona realimentación de fuerza en los ejes x,y,z. El control en tiempo real se ha diseñado usando el Sistema Operativo en Tiempo Real QuaRC de QUARC en el lado local y el Simulink Real-Time Windows TargetTM en el lado remoto. Para finalizar el resumen se destaca el impacto de esta tesis en el mundo científico a través de los resultados publicados: 2 artículos en revistas con índice de impacto , 1 artículo en una revista indexada en Sistemas, Cibernética e Informática, 7 artículos en congresos y ha obtenido un premio en la 9a. Conferencia Iberoamericana en Sistemas, Cibernética e Informática, 2010. ABSTRACT When the physical separation between the local and remote system is relatively short, the delay is not noticeable; however, when the local manipulator and the remote manipulator are at a far distance from each other, the time delay is no longer negligible and negatively influences the performance of the task. The time delay in a control system introduces a phase delay which in turn degrades the system performance and cause instability. Teleoperation systems can benefit from the ability to be in two places simultaneously, however, the use of Internet and other packet switched networks, such as Internet2, imposes varying time delays, making established control schemes to develop solutions to address these instabilities caused by different time delays. In this thesis work we present a modeling and analysis of a nonlinear bilateral teloperation system of n degrees of freedom controlled by state convergence strategy. Communication between the local and remote site is via a communication channel with time delay. The analysis presented in this work considers that the time-delay can be constant or variable. The main objectives of this work are; 1) Develop a nonlinear control schemes to ensure the stability of the teleoperated system, 2) Evaluate the system stability considering the delay in communication, and 3) Implementation of algorithms developed to test the performance of the teleoperation system in an experimental system of 3 degrees of freedom. Through the Theory of Stability of Lyapunov and the functional Lyapunov-Krasovskii, one demonstrates that the closed loop system is asymptotically stable.. The conclusions about stability were obtained by integration of the Lyapunov function and applying Barbalat Lemma. It further shows that the positions of the local and remote manipulator are synchronize when the human operator stops applying a constant force and the remote manipulator does not interact with the environment. The proposed control scheme has been validated by means of simulation and in experimental form using a developed system of real teleoperation in this doctoral thesis, which consists of a series planar manipulator of three degrees of freedom, a local manipulator, PHANTOM Omni, which is an haptic device that consists of 3 degrees of freedom (in force) and that provide feeback force in x-axis, and, z. The control in real time has been designed using the Operating system in Real time QuaRC of Quanser in the local side and the Simulink Real-Time Windows Target in the remote side. In order to finalize the summary, the highlights impact of this thesis in the scientific world are shows through the published results: 2 articles in Journals with impact factor, one article in a indexed Journal on Systemics, Cybernetics and Informatics, 7 articles in Conferences and has won an award in 9a. Conferencia Iberoamericana en Sistemas, Cibernética e Informática, 2010.

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El accidente de pérdida de refrigerante (LOCA) en un reactor nuclear es uno de los accidentes Base de Diseño más preocupantes y estudiados desde el origen del uso de la tecnología de fisión en la industria productora de energía. El LOCA ocupa, desde el punto de vista de los análisis de seguridad, un lugar de vanguardia tanto en el análisis determinista (DSA) como probabilista (PSA), cuya diferenciada perspectiva ha ido evolucionando notablemente en lo que al crédito a la actuación de las salvaguardias y las acciones del operador se refiere. En la presente tesis se aborda el análisis sistemático de de las secuencias de LOCA por pequeña y mediana rotura en diferentes lugares de un reactor nuclear de agua a presión (PWR) con fallo total de Inyección de Seguridad de Alta Presión (HPSI). Tal análisis ha sido desarrollado en base a la metodología de Análisis Integrado de Seguridad (ISA), desarrollado por el Consejo de Seguridad Nuclear (CSN) y consistente en la aplicación de métodos avanzados de simulación y PSA para la obtención de Dominios de Daño, que cuantifican topológicamente las probabilidades de éxito y daño en función de determinados parámetros inciertos. Para la elaboración de la presente tesis, se ha hecho uso del código termohidráulico TRACE v5.0 (patch 2), avalado por la NRC de los EEUU como código de planta para la simulación y análisis de secuencias en reactores de agua ligera (LWR). Los objetivos del trabajo son, principalmente: (1) el análisis exhaustivo de las secuencias de LOCA por pequeña-mediana rotura en diferentes lugares de un PWR de tres lazos de diseño Westinghouse (CN Almaraz), con fallo de HPSI, en función de parámetros de gran importancia para los transitorios, tales como el tamaño de rotura y el tiempo de retraso en la respuesta del operador; (2) la obtención y análisis de los Dominios de Daño para transitorios de LOCA en PWRs, de acuerdo con la metodología ISA; y (3) la revisión de algunos de los resultados genéricos de los análisis de seguridad para secuencias de LOCA en las mencionadas condiciones. Los resultados de la tesis abarcan tres áreas bien diferenciadas a lo largo del trabajo: (a) la fenomenología física de las secuencias objeto de estudio; (b) las conclusiones de los análisis de seguridad practicados a los transitorios de LOCA; y (c) la relevancia de las consecuencias de las acciones humanas por parte del grupo de operación. Estos resultados, a su vez, son de dos tipos fundamentales: (1) de respaldo del conocimiento previo sobre el tipo de secuencias analizado, incluido en la extensa bibliografía examinada; y (2) hallazgos en cada una de las tres áreas mencionadas, no referidos en la bibliografía. En resumidas cuentas, los resultados de la tesis avalan el uso de la metodología ISA como método de análisis alternativo y sistemático para secuencias accidentales en LWRs. ABSTRACT The loss of coolant accident (LOCA) in nuclear reactors is one of the most concerning and analized accidents from the beginning of the use of fission technology for electric power production. From the point of view of safety analyses, LOCA holds a forefront place in both Deterministic (DSA) and Probabilistic Safety Analysis (PSA), which have significantly evolved from their original state in both safeguard performance credibility and human actuation. This thesis addresses a systematic analysis of small and medium LOCA sequences, in different places of a nuclear Pressurized Water Reactor (PWR) and with total failure of High Pressure Safety Injection (HPSI). Such an analysis has been grounded on the Integrated Safety Assessment (ISA) methodology, developed by the Spanish Nuclear Regulatory Body (CSN). ISA involves the application of advanced methods of simulation and PSA for obtaining Damage Domains that topologically quantify the likelihood of success and damage regarding certain uncertain parameters.TRACE v5.0 (patch 2) code has been used as the thermalhydraulic simulation tool for the elaboration of this work. Nowadays, TRACE is supported by the US NRC as a plant code for the simulation and analysis of sequences in light water reactors (LWR). The main objectives of the work are the following ones: (1) the in-depth analysis of small and medium LOCA sequences in different places of a Westinghouse three-loop PWR (Almaraz NPP), with failed HPSI, regarding important parameters, such as break size or delay in operator response; (2) obtainment and analysis of Damage Domains related to LOCA transients in PWRs, according to ISA methodology; and (3) review some of the results of generic safety analyses for LOCA sequences in those conditions. The results of the thesis cover three separated areas: (a) the physical phenomenology of the sequences under study; (b) the conclusions of LOCA safety analyses; and (c) the importance of consequences of human actions by the operating crew. These results, in turn, are of two main types: (1) endorsement of previous knowledge about this kind of sequences, which is included in the literature; and (2) findings in each of the three aforementioned areas, not reported in the reviewed literature. In short, the results of this thesis support the use of ISA-like methodology as an alternative method for systematic analysis of LWR accidental sequences.

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Esta dissertação focaliza a trajetória do surgimento da Escola Estadual Maria Iracema Munhoz, apresentando o seu percurso desde 1890 até 1930. Para isso foi necessário fazer uma retrospectiva da educação brasileira, lembrar como surgiu São Bernardo, município onde está localizada a escola e, o surgimento da educação na cidade. O objetivo de reflexão e de pesquisa da presente dissertação foi buscar entender, pela história do passado, os problemas do presente, reconstruindo os avanços e os insucessos no processo da escolarização e das políticas públicas educacionais assumidas nesse período. A hipótese apresentada é que, nosso atraso educativo não vem tanto do que deixamos de fazer nas últimas décadas, mas do que fizemos nos séculos anteriores, em se tratando da educação.(AU)

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Esta dissertação focaliza a trajetória do surgimento da Escola Estadual Maria Iracema Munhoz, apresentando o seu percurso desde 1890 até 1930. Para isso foi necessário fazer uma retrospectiva da educação brasileira, lembrar como surgiu São Bernardo, município onde está localizada a escola e, o surgimento da educação na cidade. O objetivo de reflexão e de pesquisa da presente dissertação foi buscar entender, pela história do passado, os problemas do presente, reconstruindo os avanços e os insucessos no processo da escolarização e das políticas públicas educacionais assumidas nesse período. A hipótese apresentada é que, nosso atraso educativo não vem tanto do que deixamos de fazer nas últimas décadas, mas do que fizemos nos séculos anteriores, em se tratando da educação.(AU)

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Este trabalho analisou os fatores responsáveis pelo atraso no surgimento e no desenvolvimento dos jornais mineiros em suas principais fases: imprensa publicista, informativa e grande imprensa. As Minas, apesar de possuírem importância política e econômica, nos séculos XVIII e XIX, viram sua imprensa sempre assumir um papel secundário no país. Ela foi a sexta província a ter jornais, ficando atrás do Rio de Janeiro, Bahia, Pernambuco, Pará e Maranhão. Para entender o que deixou as Gerais nessa situação, foi necessário conhecer profundamente suas particularidades. A pesquisa demonstrou que a repressão a Inconfidência Mineira, os fluxos migratórios e as mudanças econômicas e sociais, que a província viveu no século XIX, foram responsáveis pelo atraso dos jornais mineiros. O próprio modo de ser do mineiro, a chamada mineiridade , também contribuiu para que isso ocorresse.(AU)

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Este trabalho analisou os fatores responsáveis pelo atraso no surgimento e no desenvolvimento dos jornais mineiros em suas principais fases: imprensa publicista, informativa e grande imprensa. As Minas, apesar de possuírem importância política e econômica, nos séculos XVIII e XIX, viram sua imprensa sempre assumir um papel secundário no país. Ela foi a sexta província a ter jornais, ficando atrás do Rio de Janeiro, Bahia, Pernambuco, Pará e Maranhão. Para entender o que deixou as Gerais nessa situação, foi necessário conhecer profundamente suas particularidades. A pesquisa demonstrou que a repressão a Inconfidência Mineira, os fluxos migratórios e as mudanças econômicas e sociais, que a província viveu no século XIX, foram responsáveis pelo atraso dos jornais mineiros. O próprio modo de ser do mineiro, a chamada mineiridade , também contribuiu para que isso ocorresse.(AU)

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Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host–tumor relationship involves immunomodulating cytokines and also the presence of costimulatory molecules. To examine the antitumor effect of direct in vivo gene transfer of murine interleukin 12 (IL-12) and B7-1 into tumors, we developed an adenovirus (Ad) vector, AdIL12–B7-1, that encodes the two IL-12 subunits in early region 1 (E1) and the B7-1 gene in E3 under control of the murine cytomegalovirus promoter. This vector expressed high levels of IL-12 and B7-1 in infected murine and human cell lines and in primary murine tumor cells. In mice bearing tumors derived from a transgenic mouse mammary adenocarcinoma, a single intratumoral injection with a low dose (2.5 × 107 pfu/mouse) of AdIL12–B7-1 mediated complete regression in 70% of treated animals. By contrast, administration of a similar dose of recombinant virus encoding IL-12 or B7-1 alone resulted in only a delay in tumor growth. Interestingly, coinjection of two different viruses expressing either IL-12 or B7-1 induced complete tumor regression in only 30% of animals treated at this dose. Significantly, cured animals remained tumor free after rechallenge with fresh tumor cells, suggesting that protective immunity had been induced by treatment with AdIL12–B7-1. These results support the use of Ad vectors as a highly efficient delivery system for synergistically acting molecules and show that the combination of IL-12 and B7-1 within a single Ad vector might be a promising approach for in vivo cancer therapy.

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The circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus organizes behavioral rhythms, such as the sleep–wake cycle, on a near 24-h time base and synchronizes them to environmental day and night. Light information is transmitted to the SCN by direct retinal projections via the retinohypothalamic tract (RHT). Both glutamate (Glu) and pituitary adenylyl cyclase-activating peptide (PACAP) are localized within the RHT. Whereas Glu is an established mediator of light entrainment, the role of PACAP is unknown. To understand the functional significance of this colocalization, we assessed the effects of nocturnal Glu and PACAP on phasing of the circadian rhythm of neuronal firing in slices of rat SCN. When coadministered, PACAP blocked the phase advance normally induced by Glu during late night. Surprisingly, blocking PACAP neurotransmission, with either PACAP6–38, a specific PACAP receptor antagonist, or anti-PACAP antibodies, augmented the Glu-induced phase advance. Blocking PACAP in vivo also potentiated the light-induced phase advance of the rhythm of hamster wheel-running activity. Conversely, PACAP enhanced the Glu-induced delay in the early night, whereas PACAP6–38 inhibited it. These results reveal that PACAP is a significant component of the Glu-mediated light-entrainment pathway. When Glu activates the system, PACAP receptor-mediated processes can provide gain control that generates graded phase shifts. The relative strengths of the Glu and PACAP signals together may encode the amplitude of adaptive circadian behavioral responses to the natural range of intensities of nocturnal light.

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The role of channel inactivation in the molecular mechanism of calcium (Ca2+) channel block by phenylalkylamines (PAA) was analyzed by designing mutant Ca2+ channels that carry the high affinity determinants of the PAA receptor site [Hockerman, G. H., Johnson, B. D., Scheuer, T., and Catterall, W. A. (1995) J. Biol. Chem. 270, 22119–22122] but inactivate at different rates. Use-dependent block by PAAs was studied after expressing the mutant Ca2+ channels in Xenopus oocytes. Substitution of single putative pore-orientated amino acids in segment IIIS6 by alanine (F-1499-A, F-1500-A, F-1510-A, I-1514-A, and F-1515-A) gradually slowed channel inactivation and simultaneously reduced inhibition of barium currents (IBa) by (−)D600 upon depolarization by 100 ms steps at 0.1 Hz. This apparent reduction in drug sensitivity was only evident if test pulses were applied at a low frequency of 0.1 Hz and almost disappeared at the frequency of 1 Hz. (−)D600 slowed IBa recovery after maintained membrane depolarization (1–3 sec) to a comparable extent in all channel constructs. A drug-induced delay in the onset of IBa recovery from inactivation suggests that PAAs promote the transition to a deep inactivated channel conformation. These findings indicate that apparent PAA sensitivity of Ca2+ channels is not only defined by drug interaction with its receptor site but also crucially dependent on intrinsic gating properties of the channel molecule. A molecular model for PAA-Ca2+ channel interaction that accounts for the relationship between drug induced inactivation and channel block by PAA is proposed.

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Many eukaryotic cell surface proteins are anchored in the lipid bilayer through glycosylphosphatidylinositol (GPI). GPI anchors are covalently attached in the endoplasmic reticulum (ER). The modified proteins are then transported through the secretory pathway to the cell surface. We have identified two genes in Saccharomyces cerevisiae, LAG1 and a novel gene termed DGT1 (for “delayed GPI-anchored protein transport”), encoding structurally related proteins with multiple membrane-spanning domains. Both proteins are localized to the ER, as demonstrated by immunofluorescence microscopy. Deletion of either gene caused no detectable phenotype, whereas lag1Δ dgt1Δ cells displayed growth defects and a significant delay in ER-to-Golgi transport of GPI-anchored proteins, suggesting that LAG1 and DGT1 encode functionally redundant or overlapping proteins. The rate of GPI anchor attachment was not affected, nor was the transport rate of several non–GPI-anchored proteins. Consistent with a role of Lag1p and Dgt1p in GPI-anchored protein transport, lag1Δ dgt1Δ cells deposit abnormal, multilayered cell walls. Both proteins have significant sequence similarity to TRAM, a mammalian membrane protein thought to be involved in protein translocation across the ER membrane. In vivo translocation studies, however, did not detect any defects in protein translocation in lag1Δ dgt1Δ cells, suggesting that neither yeast gene plays a role in this process. Instead, we propose that Lag1p and Dgt1p facilitate efficient ER-to-Golgi transport of GPI-anchored proteins.

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Antigen presentation to CD4+ T lymphocytes requires transport of newly synthesized major histocompatibility complex (MHC) class II molecules to the endocytic pathway, where peptide loading occurs. This step is mediated by a signal located in the cytoplasmic tail of the MHC class II-associated Ii chain, which directs the MHC class II-Ii complexes from the trans-Golgi network (TGN) to endosomes. The subcellular machinery responsible for the specific targeting of MHC class II molecules to the endocytic pathway, as well as the first compartments these molecules enter after exit from the TGN, remain unclear. We have designed an original experimental approach to selectively analyze this step of MHC class II transport. Newly synthesized MHC class II molecules were caused to accumulate in the Golgi apparatus and TGN by incubating the cells at 19°C, and early endosomes were functionally inactivated by in vivo cross-linking of transferrin (Tf) receptor–containing endosomes using Tf-HRP complexes and the HRP-insoluble substrate diaminobenzidine. Inactivation of Tf-containing endosomes caused a marked delay in Ii chain degradation, peptide loading, and MHC class II transport to the cell surface. Thus, early endosomes appear to be required for delivery of MHC class II molecules to the endocytic pathway. Under cross-linking conditions, most αβIi complexes accumulated in tubules and vesicles devoid of γ-adaptin and/or mannose-6-phosphate receptor, suggesting an AP1-independent pathway for the delivery of newly synthesized MHC class II molecules from the TGN to endosomes.

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Most mammalian cells exhibit transient delays in the G1 and G2 phases of the cell cycle after treatment with radiation or radiomimetic compounds. p53 is required for the arrest in G1, which provides time for DNA repair. Recently, a role of p53 in the G2/M transition has also been suggested. However, it has been reported that the presence of functional p53 does not always correlate with the induction of these checkpoints. To precisely assess the role of p53 in activating cell cycle checkpoints and in cell survival after radiation, we studied the response of two isogenic human fibrosarcoma cell lines differing in their p53 status (wild type or mutant). We found that when irradiated cells undergo a wild-type p53-dependent G1 arrest, they do not subsequently arrest in G2. Moreover, wild-type p53 cells irradiated past the G1 checkpoint arrest in G2 but do not delay in the subsequent G1 phase. Furthermore, in these cell lines, which do not undergo radiation-induced apoptosis, the wild-type p53 cell line exhibited a greater radioresistance in terms of clonogenic survival. These results suggest that the two checkpoints may be interrelated, perhaps through a control system that determines, depending on the extent of the damage, whether the cell needs to arrest cell cycle progression at the subsequent checkpoint for further repair. p53 could be a crucial component of this control system.

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Familial structural rearrangements of chromosomes represent a factor of malformation risk that could vary over a large range, making genetic counseling difficult. However, they also represent a powerful tool for increasing knowledge of the genome, particularly by studying breakpoints and viable imbalances of the genome. We have developed a collaborative database that now includes data on more than 4100 families, from which we have developed a web site called HC Forum® (http://HCForum.imag.fr). It offers geneticists assistance in diagnosis and in genetic counseling by assessing the malformation risk with statistical models. For researchers, interactive interfaces exhibit the distribution of chromosomal breakpoints and of the genome regions observed at birth in trisomy or in monosomy. Dedicated tools including an interactive pedigree allow electronic submission of data, which will be anonymously shown in a forum for discussions. After validation, data are definitively registered in the database with the email of the sender, allowing direct location of biological material. Thus HC Forum® constitutes a link between diagnosis laboratories and genome research centers, and after 1 year, more than 700 users from about 40 different countries already exist.

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Exposure of yeast cells to an increase in external osmolarity induces a temporary growth arrest. Recovery from this stress is mediated by the accumulation of intracellular glycerol and the transcription of several stress response genes. Increased external osmolarity causes a transient accumulation of 1N and 2N cells and a concomitant depletion of S phase cells. Hypertonic stress triggers a cell cycle delay in G2 phase cells that appears distinct from the morphogenesis checkpoint, which operates in early S phase cells. Hypertonic stress causes a decrease in CLB2 mRNA, phosphorylation of Cdc28p, and inhibition of Clb2p-Cdc28p kinase activity, whereas Clb2 protein levels are unaffected. Like the morphogenesis checkpoint, the osmotic stress-induced G2 delay is dependent upon the kinase Swe1p, but is not tightly correlated with inhibition of Clb2p-Cdc28p kinase activity. Thus, deletion of SWE1 does not prevent the hypertonic stress-induced inhibition of Clb2p-Cdc28p kinase activity. Mutation of the Swe1p phosphorylation site on Cdc28p (Y19) does not fully eliminate the Swe1p-dependent cell cycle delay, suggesting that Swe1p may have functions independent of Cdc28p phosphorylation. Conversely, deletion of the mitogen-activated protein kinase HOG1 does prevent Clb2p-Cdc28p inhibition by hypertonic stress, but does not block Cdc28p phosphorylation or alleviate the cell cycle delay. However, Hog1p does contribute to proper nuclear segregation after hypertonic stress in cells that lack Swe1p. These results suggest a hypertonic stress-induced cell cycle delay in G2 phase that is mediated in a novel way by Swe1p in cooperation with Hog1p.