Characterisation of the influence function non-additivities for a 1024-actuator MEMS deformable mirror

In order to evaluate the potential of MEMS deformable mirrors for open-loop applications, a complete calibration process was performed on a 1024-actuator mirror. The mirror must be perfectly calibrated to obtain deterministic membrane deflection. The actuator's stroke-voltage relationship and the effect of the non- additivity of the influence functions are studied and finally integrated in an open-loop control process. This experiment aimed at minimizing the residual error obtained in open-loop control.Comment: 6 pages, 9 figures, Proceedings of the 1st AO for ELT conference, June 2009, Pari

Developmental specialization of the left parietal cortex for the semantic representation of Arabic numerals: an fMR-adaptation study

The way the human brain constructs representations of numerical symbols is poorly understood. While increasing evidence from neuroimaging studies has indicated that the intraparietal sulcus (IPS) becomes increasingly specialized for symbolic numerical magnitude representation over developmental time, the extent to which these changes are associated with age-related differences in symbolic numerical magnitude representation or with developmental changes in non-numerical processes, such as response selection, remains to be uncovered. To address these outstanding questions we investigated developmental changes in the cortical representation of symbolic numerical magnitude in 6- to 14-year-old children using a passive functional magnetic resonance imaging adaptation design, thereby mitigating the influence of response selection. A single-digit Arabic numeral was repeatedly presented on a computer screen and interspersed with the presentation of novel digits deviating as a function of numerical ratio (smaller/larger number). Results demonstrated a correlation between age and numerical ratio in the left IPS, suggesting an age-related increase in the extent to which numerical symbols are represented in the left IPS. Brain activation of the right IPS was modulated by numerical ratio but did not correlate with age, indicating hemispheric differences in IPS engagement during the development of symbolic numerical representation

Using Heat to Characterize Streambed Water Flux Variability in Four Stream Reaches

Estimates of streambed water fl ux are needed for the interpretation of streambed chemistry and reactions. Continuous temperature and head monitoring in stream reaches within four agricultural watersheds (Leary Weber Ditch, IN; Maple Creek, NE; DR2 Drain, WA; and Merced River, CA) allowed heat to be used as a tracer to study the temporal and spatial variability of fluxes through the streambed. Synoptic methods (seepage meter and differential discharge measurements) were compared with estimates obtained by using heat as a tracer. Water flux was estimated by modeling one-dimensional vertical flow of water and heat using the model VS2DH. Flux was influenced by physical heterogeneity of the stream channel and temporal variability in stream and ground-water levels. During most of the study period (April–December 2004), flux was upward through the streambeds. At the IN, NE, and CA sites, high-stage events resulted in rapid reversal of flow direction inducing short-term surface-water flow into the streambed. During late summer at the IN site, regional ground-water levels dropped, leading to surface-water loss to ground water that resulted in drying of the ditch. Synoptic measurements of flux generally supported the model flux estimates. Water flow through the streambed was roughly an order of magnitude larger in the humid basins (IN and NE) than in the arid basins (WA and CA). Downward flux, in response to sudden high streamflows, and seasonal variability in flux was most pronounced in the humid basins and in high conductivity zones in the streambed

Using Heat to Characterize Streambed Water Flux Variability in Four Stream Reaches

Estimates of streambed water fl ux are needed for the interpretation of streambed chemistry and reactions. Continuous temperature and head monitoring in stream reaches within four agricultural watersheds (Leary Weber Ditch, IN; Maple Creek, NE; DR2 Drain, WA; and Merced River, CA) allowed heat to be used as a tracer to study the temporal and spatial variability of fluxes through the streambed. Synoptic methods (seepage meter and differential discharge measurements) were compared with estimates obtained by using heat as a tracer. Water flux was estimated by modeling one-dimensional vertical flow of water and heat using the model VS2DH. Flux was influenced by physical heterogeneity of the stream channel and temporal variability in stream and ground-water levels. During most of the study period (April–December 2004), flux was upward through the streambeds. At the IN, NE, and CA sites, high-stage events resulted in rapid reversal of flow direction inducing short-term surface-water flow into the streambed. During late summer at the IN site, regional ground-water levels dropped, leading to surface-water loss to ground water that resulted in drying of the ditch. Synoptic measurements of flux generally supported the model flux estimates. Water flow through the streambed was roughly an order of magnitude larger in the humid basins (IN and NE) than in the arid basins (WA and CA). Downward flux, in response to sudden high streamflows, and seasonal variability in flux was most pronounced in the humid basins and in high conductivity zones in the streambed

Eurasian-Origin Gene Segments Contribute to the Transmissibility, Aerosol Release, and Morphology of the 2009 Pandemic H1N1 Influenza Virus

The epidemiological success of pandemic and epidemic influenza A viruses relies on the ability to transmit efficiently from person-to-person via respiratory droplets. Respiratory droplet (RD) transmission of influenza viruses requires efficient replication and release of infectious influenza particles into the air. The 2009 pandemic H1N1 (pH1N1) virus originated by reassortment of a North American triple reassortant swine (TRS) virus with a Eurasian swine virus that contributed the neuraminidase (NA) and M gene segments. Both the TRS and Eurasian swine viruses caused sporadic infections in humans, but failed to spread from person-to-person, unlike the pH1N1 virus. We evaluated the pH1N1 and its precursor viruses in a ferret model to determine the contribution of different viral gene segments on the release of influenza virus particles into the air and on the transmissibility of the pH1N1 virus. We found that the Eurasian-origin gene segments contributed to efficient RD transmission of the pH1N1 virus likely by modulating the release of influenza viral RNA-containing particles into the air. All viruses replicated well in the upper respiratory tract of infected ferrets, suggesting that factors other than viral replication are important for the release of influenza virus particles and transmission. Our studies demonstrate that the release of influenza viral RNA-containing particles into the air correlates with increased NA activity. Additionally, the pleomorphic phenotype of the pH1N1 virus is dependent upon the Eurasian-origin gene segments, suggesting a link between transmission and virus morphology. We have demonstrated that the viruses are released into exhaled air to varying degrees and a constellation of genes influences the transmissibility of the pH1N1 virus

The Role of the Mitotic Spindle Checkpoint in Chemotherapy-Induced Apoptosis

The mitotic spindle assembly checkpoint (SCP) is a signal transduction pathway that ensures proper chromosome segregation during mitosis by inhibiting the onset of anaphase until all chromosomes are properly aligned. It requires a group of highly conserved proteins including Mad1, Mad2, Bub1, BubR1, Mps1 and the so-called chromosomal passenger complex comprising survivin, borealin, INCENP and the Aurora B kinase. The SCP ensures chromosomal stability during a normal mitosis, but it is also activated by chemotherapeutic drugs that interfere with chromosome alignment leading to a prolonged mitotic arrest. Subsequently tetraploid cells exit mitosis – a process termed "mitotic slippage"–, thereby activating the so-called pseudo-G1 checkpoint, which arrests cells p53-dependently at the G1/S border. Failure of this second fail-safe mechanism might promote cancerogenesis via polyploidization and induction of genomic instability. The present work has defined the pseudo-G1 checkpoint as dependent on p53 and a functional SCP. Moreover, an additional SCP-independent checkpoint is activated in G2, which prevents polyploid cells from entering the next mitosis. Thus, multiple checkpoints cooperate to prevent further polyploidization after mitotic failure. Antimitotic substances are among the most frequently used chemotherapeutics. However, the mechanisms of mitosis-associated apoptosis and chemotherapy resistance are largely unknown. During the course of my work I demonstrated that the SCP is required for the induction of apoptosis in response to various antimitotic drugs. Specifically, Mad2 was shown to be a central proapoptotic factor after treatment with drugs that impair kinetochore tension, which do not only include spindle poisons like taxol, but surprisingly also DNA damaging agents like topoisomerase II inhibitors. A clinically relevant mitosis-associated chemotherapeutic strategy is the induction of “mitotic catastrophe”, a poorly defined form of cell death. Abrogation of the activated G2 DNA damage checkpoint by Chk1 kinase inhibitors selectively forces p53-negative cells into mitosis, resulting in mitosis-associated cell death. This work shows that “mitotic catastrophe” is a mitosis-specific form of apoptosis, which is associated with SCP activation and requires the proapoptotic function of Mad2. Surprisingly, I found that the proapoptotic pathway during mitosis was counteracted by survival pathways comprising survivin, Aurora B and Cdk1. Therefore, genetic or pharmacological abrogation of the survival pathways synergistically enhances mitotic apoptosis and suggests a highly improved strategy for anticancer chemotherapy. My results, which demonstrate an important role of the SCP in mediating chemotherapy-induced apoptosis, suggest that SCP defects might account for drug resistance, posing a serious problem in the clinic. Therefore, alternative chemotherapeutic approaches independent of full SCP functionality are urgently needed. Interestingly, the observation that the SCP is essential for cancer cell viability gives rise to a novel concept of chemotherapy, which targets the SCP. In fact, our lab has identified a potent pharmacological SCP inhibitor and I was able to demonstrate that this inhibitor induces apoptosis in cancer cells, even those resistant to spindle poisons due to SCP defects

The Role of the Mitotic Spindle Checkpoint in Chemotherapy-Induced Apoptosis

The mitotic spindle assembly checkpoint (SCP) is a signal transduction pathway that ensures proper chromosome segregation during mitosis by inhibiting the onset of anaphase until all chromosomes are properly aligned. It requires a group of highly conserved proteins including Mad1, Mad2, Bub1, BubR1, Mps1 and the so-called chromosomal passenger complex comprising survivin, borealin, INCENP and the Aurora B kinase. The SCP ensures chromosomal stability during a normal mitosis, but it is also activated by chemotherapeutic drugs that interfere with chromosome alignment leading to a prolonged mitotic arrest. Subsequently tetraploid cells exit mitosis – a process termed "mitotic slippage"–, thereby activating the so-called pseudo-G1 checkpoint, which arrests cells p53-dependently at the G1/S border. Failure of this second fail-safe mechanism might promote cancerogenesis via polyploidization and induction of genomic instability. The present work has defined the pseudo-G1 checkpoint as dependent on p53 and a functional SCP. Moreover, an additional SCP-independent checkpoint is activated in G2, which prevents polyploid cells from entering the next mitosis. Thus, multiple checkpoints cooperate to prevent further polyploidization after mitotic failure. Antimitotic substances are among the most frequently used chemotherapeutics. However, the mechanisms of mitosis-associated apoptosis and chemotherapy resistance are largely unknown. During the course of my work I demonstrated that the SCP is required for the induction of apoptosis in response to various antimitotic drugs. Specifically, Mad2 was shown to be a central proapoptotic factor after treatment with drugs that impair kinetochore tension, which do not only include spindle poisons like taxol, but surprisingly also DNA damaging agents like topoisomerase II inhibitors. A clinically relevant mitosis-associated chemotherapeutic strategy is the induction of “mitotic catastrophe”, a poorly defined form of cell death. Abrogation of the activated G2 DNA damage checkpoint by Chk1 kinase inhibitors selectively forces p53-negative cells into mitosis, resulting in mitosis-associated cell death. This work shows that “mitotic catastrophe” is a mitosis-specific form of apoptosis, which is associated with SCP activation and requires the proapoptotic function of Mad2. Surprisingly, I found that the proapoptotic pathway during mitosis was counteracted by survival pathways comprising survivin, Aurora B and Cdk1. Therefore, genetic or pharmacological abrogation of the survival pathways synergistically enhances mitotic apoptosis and suggests a highly improved strategy for anticancer chemotherapy. My results, which demonstrate an important role of the SCP in mediating chemotherapy-induced apoptosis, suggest that SCP defects might account for drug resistance, posing a serious problem in the clinic. Therefore, alternative chemotherapeutic approaches independent of full SCP functionality are urgently needed. Interestingly, the observation that the SCP is essential for cancer cell viability gives rise to a novel concept of chemotherapy, which targets the SCP. In fact, our lab has identified a potent pharmacological SCP inhibitor and I was able to demonstrate that this inhibitor induces apoptosis in cancer cells, even those resistant to spindle poisons due to SCP defects