Myocardial Relaxation Is Accelerated by Fast Stretch, Not Reduced Afterload

Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the speed of myocardial relengthening at end systole (end systolic strain rate), and not afterload, modulates relaxation rate and tested this hypothesis using electrically-stimulated trabeculae from mice, rats, and humans. We used load-clamp techniques to vary afterload and end systolic strain rate independently. Our data show that the rate of relaxation increases monotonically with end systolic strain rate but is not altered by afterload. Computer simulations mimic this behavior and suggest that fast relengthening quickens relaxation by accelerating the detachment of cross-bridges. The relationship between relaxation rate and strain rate is novel and upends the prevailing theory that afterload modifies relaxation. In conclusion, myocardial relaxation is mechanically modified by the rate of stretch at end systole. The rate of myocardial relengthening at end systole may be a new diagnostic indicator or target for treatment of diastolic dysfunction

Feedback in the local LBG Analog Haro 11 as probed by far-UV and X-ray observations

We have re-analyzed FUSE data and obtained new Chandra observations of Haro 11, a local (D_L=88 Mpc) UV luminous galaxy. Haro 11 has a similar far-UV luminosity (10^10.3 L_\odot), UV surface brightness (10^9.4 L_\odot kpc^-2), SFR, and metallicity to that observed in Lyman Break Galaxies (LBGs). We show that Haro 11 has extended, soft thermal (kT~0.68 keV) X-ray emission with a luminosity and size which scales with the physical properties (e.g. SFR, stellar mass) of the host galaxy. An enhanced alpha/Fe, ratio of ~4 relative to solar abundance suggests significant supernovae enrichment. These results are consistent with the X-ray emission being produced in a shock between a supernovae driven outflow and the ambient material. The FUV spectra show strong absorption lines similar to those observed in LBG spectra. A blueshifted absorption component is identified as a wind outflowing at ~200-280 km/s. OVI\lambda\lambda1032,1038 emission, the dominant cooling mechanism for coronal gas at T~10^5.5 K is also observed. If associated with the outflow, the luminosity of the OVI emission suggests that <20% of the total mechanical energy from the supernovae and solar winds is being radiated away. This implies that radiative cooling through OVI is not significantly inhibiting the growth of the outflowing gas. In contradiction to the findings of Bergvall et al 2006, we find no convincing evidence of Lyman continuum leakage in Haro 11. We conclude that the wind has not created a `tunnel' allowing the escape of a significant fraction of Lyman continuum photons and place a limit on the escape fraction of f_{esc}<2%. Overall, both Haro 11 and a previously observed LBG analogue VV 114, provide an invaluable insight into the X-ray and FUV properties of high redshift LBGs.Comment: Accepted for publication in ApJ, 40 pages, 17 figure

Nuevo Corinto: A Chiefly Village in Northeastern Costa Rica

Archaeological research at Nuevo Corinto has provided information on the emergence of complex village patterns in northeastern Costa Rica. This includes an improved chronology of in situ culture change over a 3000-year period. The consolidation of an architectural core began ca. AD 400-600 with the principal period of construction of circular elevated platforms for supporting domestic structures, reaching peak construction ca. AD 700-1100. Nuevo Corinto, together with neighboring sites, appears to have been a major node in trade networks extending from the Caribbean to the Pacific coasts. Our research has provided details on the emergence and growth of architectural units and hydraulic features in this village, a center of manufacturing, trade, and social hierarchy in the Caribbean lowlands.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro de Investigaciones Antropológicas (CIAN)UCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Ciencias Sociales::Escuela de Antropologí

Fluorescent Affibody Peptide Penetration in Glioma Margin Is Superior to Full Antibody

Object: Fluorescence imaging has the potential to significantly improve neurosurgical resection of oncologic lesions through improved differentiation between normal and cancerous tissue at the tumor margins. In order to successfully mark glioma tissue a fluorescent tracer must have the ability to penetrate through the blood brain barrier (BBB) and provide delineation in the tumor periphery where heterogeneously intact BBB may exist. In this study it was hypothesized that, due to its smaller size, fluorescently labeled anti-EGFR Affibody protein (~7 kDa) would provide a more clear delineation of the tumor margin than would fluorescently labeled cetuximab, a full antibody (~150 kDa) to the epidermal growth factor receptor (EGFR). Methods: Cetuximab and anti-EGFR targeted Affibody were conjugated to two different fluorescent dyes (both emitting in the near-infrared) and injected intravenously into 6 athymic mice which were inoculated orthotopically with green fluorescent protein (GFP) expressing human U251 glioma cells. Each mouse was sacrificed at 1-h post injection, at which time brains were removed, snap frozen, sectioned and quantitatively analyzed for fluorescence distribution. Results: Ex vivo analysis showed on average, nearly equal concentrations of cetuximab and Affibody within the tumor (on average Affibody made up 49 ± 6% of injected protein), however, the cetuximab was more confined to the center of the tumor with Affibody showing significantly higher concentrations at the tumor periphery (on average Affibody made up 72 ± 15% of injected protein in the outer 50 um of the tumor). Further ex vivo analysis of detection studies showed that the Affibody provided superior discrimination for differentiation of tumor from surrounding normal brain. Conclusions: The present study indicates that fluorescently labeled anti-EGFR Affibody can provide significantly better delineation of tumor margins than a fluorescently labeled anti-EGFR antibody and shows considerable potential for guiding margin detection during neurosurgery

Noninvasive Measurement of Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Allowing Detection of Murine Glioma In Vivo

Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence is studied as a contrast agent for noninvasive detection of murine glioma, using the fluorescence-to-transmission ratio measured through the cranium. Signals measured prior to administration of ALA are very similar between control animals, 9L-GFP, and U251 tumor-bearing animals. However, 2 h after ALA administration, the PpIX signal from both tumor-bearing groups is significantly higher than the control group (9L-GFP group p-value=0.016, and U251 group p-value=0.004, relative to the control group). The variance in signal from the 9L-GFP group is much larger than either the control group or the U251 group, which is consistent with higher intrinsic PpIX fluorescence heterogeneity as seen in situ at ex vivo analysis. Decreasing the skin PpIX fluorescence via intentional photobleaching using red light (635 nm) is examined as a tool for increasing PpIX contrast between the tumor-bearing and control groups. The red light bleaching is found to increase the ability to accurately quantify PpIX fluorescence in vivo, but decreases the specificity of detection between tumor-bearing and nontumor-bearing groups

Quantitative Imaging of Scattering Changes Associated with Epithelial Proliferation, Necrosis and Fibrosis in Tumors Using Microsampling Reflectance Spectroscopy

Highly localized reflectance measurements can be used to directly quantify scatter changes in tissues. We present a microsampling approach that is used to raster scan tumors to extract parameters believed to be related to the tissue ultrastructure. A confocal reflectance imager was developed to examine scatter changes across pathologically distinct regions within tumor tissues. Tissue sections from two murine tumors, AsPC-1 pancreas tumor and the Mat-LyLu Dunning prostate tumor, were imaged. After imaging, histopathology-guided region-of-interest studies of the images allowed analysis of the variations in scattering resulting from differences in tissue ultra-structure. On average, the median scatter power of tumor cells with high proliferation index (HPI) was about 26% less compared to tumor cells with low proliferation index (LPI). Necrosis exhibited the lowest scatter power signature across all the tissue types considered, with about 55% lower median scatter power than LPI tumor cells. Additionally, the level and maturity of the tumor\u27s fibroplastic response was found to influence the scatter signal. This approach to scatter visualization of tissue ultrastructure in situ could provide a unique tool for guiding surgical resection, but this kind of interpretation into what the signal means relative to the pathology is required before proceeding to clinical studies

Delayed Sternal Closure Does Not Reduce Complications Associated with Coagulopathy and Right Ventricular Failure After Left Ventricular Assist Device Implantation

Delayed sternal closure (DSC) is occasionally adopted after implantation of left ventricular assist device (LVAD). Recent studies suggest that DSC be used for high risk group of patients with coagulopathy, hemodynamic instability or right ventricular failure. However, whether DSC is efficacious for bleeding complication or right ventricular failure is not known. This study is single center analysis of 52 patients, who underwent LVAD implantation. Of those 52 patients, 40 consecutive patients underwent DSC routinely. The sternum was left open with vacuum assist device after implantation of LVAD. Perioperative outcome of the patients who underwent routine DSC were compared with 12 patients who had immediate sternal closure (IC). Mean Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level of IC group and DSC group were 2.7 and 2.6, respectively. Postoperative bleeding (643 vs. 1469 ml, p \u3c 0.001), duration of inotropic support (109 vs. 172 h, p = 0.034), and time to extubation (26 vs. 52 h, p = 0.005) were significantly increased in DSC group. Length of ICU stay (14 vs. 15 days, p = 0.234) and hospital stay (28 vs. 20 days, p = 0.145) were similar. Incidence of right ventricular failure and tamponade were similar in the two groups. Routine DSC after implantation of an LVAD did not prove to be beneficial in reducing complications associated with coagulopathy and hemodynamic instability including cardiac tamponade or right ventricular failure. We suggest that DSC be selectively applied for patients undergoing LVAD implant

Discovery of a Nearby Low-Surface-Brightness Spiral Galaxy

During the course of a search for compact, isolated gas clouds moving with anomalous velocities in or near our own Galaxy (Braun and Burton 1998 A&A, in press), we have discovered, in the data of the Leiden/Dwingeloo survey (Hartmann and Burton 1997, Atlas of Galactic Neutral Hydrogen, CUP) of Galactic hydrogen, the HI signature of a large galaxy, moving at a recession velocity of 282 km/s, with respect to our Galaxy. Deep multicolor and spectroscopic optical observations show the presence of star formation in scattered HII regions; radio HI synthesis interferometry confirms that the galaxy is rich in HI and has the rotation signature of a spiral galaxy; a submillimeter observation failed to detect the CO molecule. The radio and optical evidence combined suggest its classification as a low-surface-brightness spiral galaxy. It is located in close spatial and kinematic proximity to the galaxy NGC 6946. The newly-discovered galaxy, which we call Cepheus 1, is at a distance of about 6 Mpc. It is probably to be numbered amongst the nearest few LSB spirals.Comment: 13 page LaTeX, requires aastex, 4 GIF figures. Accepted for publication in the AJ, January 199