Passive and active ventricular elastances of the left ventricle

BACKGROUND: Description of the heart as a pump has been dominated by models based on elastance and compliance. Here, we are presenting a somewhat new concept of time-varying passive and active elastance. The mathematical basis of time-varying elastance of the ventricle is presented. We have defined elastance in terms of the relationship between ventricular pressure and volume, as: dP = EdV + VdE, where E includes passive (E(p)) and active (E(a)) elastance. By incorporating this concept in left ventricular (LV) models to simulate filling and systolic phases, we have obtained the time-varying expression for E(a )and the LV-volume dependent expression for E(p). METHODS AND RESULTS: Using the patient's catheterization-ventriculogram data, the values of passive and active elastance are computed. E(a )is expressed as: [Image: see text]; E(p)is represented as: [Image: see text]. E(a )is deemed to represent a measure of LV contractility. Hence, Peak dP/dt and ejection fraction (EF) are computed from the monitored data and used as the traditional measures of LV contractility. When our computed peak active elastance (E(a,max)) is compared against these traditional indices by linear regression, a high degree of correlation is obtained. As regards E(p), it constitutes a volume-dependent stiffness property of the LV, and is deemed to represent resistance-to-filling. CONCLUSIONS: Passive and active ventricular elastance formulae can be evaluated from a single-beat P-V data by means of a simple-to-apply LV model. The active elastance (E(a)) can be used to characterize the ventricle's contractile state, while passive elastance (E(p)) can represent a measure of resistance-to-filling

Domain wall brane in squared curvature gravity

We suggest a thick braneworld model in the squared curvature gravity theory. Despite the appearance of higher order derivatives, the localization of gravity and various bulk matter fields is shown to be possible. The existence of the normalizable gravitational zero mode indicates that our four-dimensional gravity is reproduced. In order to localize the chiral fermions on the brane, two types of coupling between the fermions and the brane forming scalar is introduced. The first coupling leads us to a Schr\"odinger equation with a volcano potential, and the other a P\"oschl-Teller potential. In both cases, the zero mode exists only for the left-hand fermions. Several massive KK states of the fermions can be trapped on the brane, either as resonant states or as bound states.Comment: 18 pages, 5 figures and 1 table, references added, improved version to be published in JHE

Management of Hepatic Angiomyolipoma

Preoperative diagnosis of hepatic angiomyolipoma is difficult, and the treatment for it remains controversial. The aim of this study is to review our experience in the treatment of hepatic angiomyolipoma and to propose a treatment strategy for this disease. We retrospectively collected the clinical, imaging, and pathological features of patients with hepatic angiomyolipoma. Immunohistochemical studies with antibodies for HMB-45, actin, S-100, cytokeratin, vimentin, and c-kit were performed. Treatment experience and long-term follow-up results are summarized. During a period of 9 years, 10 patients with hepatic angiomyolipoma were treated at our hospital. There was marked female predominance (nine patients). Nine patients received surgical resection without complications. One patient received nonoperative management with biopsy and follow-up. One patient died 11 months after surgery because of recurrent disease. We propose all symptomatic patients should receive surgical resection for hepatic angiomyolipoma. Conservative management with close follow-up is suggested in patients with asymptomatic tumors and meet the following criteria: (1) tumor size smaller than 5 cm, (2) angiomyolipoma proved through fine needle aspiration biopsy, (3) patients with good compliance, and (4) not a hepatitis virus carrier

Antibody Engineering Using Phage Display with a Coiled-Coil Heterodimeric Fv Antibody Fragment

A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to VH and VL for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of VH frameworks and VH-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering

Cytotoxic activity of proteins isolated from extracts of Corydalis cava tubers in human cervical carcinoma HeLa cells

<p>Abstract</p> <p>Background</p> <p><it>Corydalis cava </it>Schweigg. & Koerte, the plant of numerous pharmacological activities, together with the studied earlier by our group <it>Chelidonium majus </it>L. (Greater Celandine), belong to the family <it>Papaveraceae</it>. The plant grows in Central and South Europe and produces the sizeable subterraneous tubers, empty inside, which are extremely resistant to various pathogen attacks. The <it>Corydalis sp. </it>tubers are a rich source of many biologically active substances, with the extensive use in European and Asian folk medicine. They have analgetic, sedating, narcotic, anti-inflammatory, anti-allergic and anti-tumour activities. On the other hand, there is no information about possible biological activities of proteins contained in <it>Corydalis cava </it>tubers.</p> <p>Methods</p> <p>Nucleolytic proteins were isolated from the tubers of <it>C. cava </it>by separation on a heparin column and tested for DNase activity. Protein fractions showing nucleolytic activity were tested for cytotoxic activity in human cervical carcinoma HeLa cells. Cultures of HeLa cells were conducted in the presence of three protein concentrations: 42, 83 and 167 ng/ml during 48 h. Viability of cell cultures was appraised using XTT colorimetric test. Protein fractions were separated and protein bands were excised and sent for identification by mass spectrometry (LC-ESI-MS/MS).</p> <p>Results</p> <p>The studied protein fractions showed an inhibiting effect on mitochondrial activity of HeLa cells, depending on the administered dose of proteins. The most pronounced effect was obtained with the highest concentration of the protein (167 ng/ml) - 43.45 ± 3% mitochondrial activity of HeLa cells were inhibited. Mass spectrometry results for the proteins of applied fractions showed that they contained plant defense- and pathogenesis-related (PR) proteins.</p> <p>Conclusions</p> <p>The cytotoxic effect of studied proteins toward HeLa cell line cells has been evident and dependent on increasing dose of the protein. The present study, most probably, represents the first investigations on the effect of purified PR proteins from tuber extracts of a pharmacologically active plant on cell lines.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Synthesis of Monodisperse Nanocrystals via Microreaction: Open-to-Air Synthesis with Oleylamine as a Coligand

Microreaction provides a controllable tool to synthesize CdSe nanocrystals (NCs) in an accelerated fashion. However, the surface traps created during the fast growth usually result in low photoluminescence (PL) efficiency for the formed products. Herein, the reproducible synthesis of highly luminescent CdSe NCs directly in open air was reported, with a microreactor as the controllable reaction tool. Spectra investigation elucidated that applying OLA both in Se and Cd stock solutions could advantageously promote the diffusion between the two precursors, resulting in narrow full-width-at-half maximum (FWHM) of PL (26 nm). Meanwhile, the addition of OLA in the source solution was demonstrated helpful to improve the reactivity of Cd monomer. In this case, the focus of size distribution was accomplished during the early reaction stage. Furthermore, if the volume percentage (vol.%) of OLA in the precursors exceeded a threshold of 37.5%, the resulted CdSe NCs demonstrated long-term fixing of size distribution up to 300 s. The observed phenomena facilitated the preparation of a size series of monodisperse CdSe NCs merely by the variation of residence time. With the volume percentage of OLA as 37.5% in the source solution, a 78 nm tuning of PL spectra (from 507 to 585) was obtained through the variation of residence time from 2 s to 160 s, while maintaining narrow FMWH of PL (26–31 nm) and high QY of PL (35–55%)

The POM Monoclonals: A Comprehensive Set of Antibodies to Non-Overlapping Prion Protein Epitopes

PrPSc, a misfolded and aggregated form of the cellular prion protein PrPC, is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrPC in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrPC and PrPSc. Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrPC. Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrPC. Some of these antibodies recognize epitopes that are resilient to protease digestion in PrPSc. Other antibodies immunoprecipitate PrPC, but not PrPSc. A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrPC and PrPSc. Amino-proximal antibodies were found to react with repetitive PrPC epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays

Functional Organization of Locomotor Interneurons in the Ventral Lumbar Spinal Cord of the Newborn Rat

Although the mammalian locomotor CPG has been localized to the lumbar spinal cord, the functional-anatomical organization of flexor and extensor interneurons has not been characterized. Here, we tested the hypothesis that flexor and extensor interneuronal networks for walking are physically segregated in the lumbar spinal cord. For this purpose, we performed optical recordings and lesion experiments from a horizontally sectioned lumbar spinal cord isolated from neonate rats. This ventral hemi spinal cord preparation produces well-organized fictive locomotion when superfused with 5-HT/NMDA. The dorsal surface of the preparation was visualized using the Ca2+ indicator fluo-4 AM, while simultaneously monitoring motor output at ventral roots L2 and L5. Using calcium imaging, we provided a general mapping view of the interneurons that maintained a stable phase relationship with motor output. We showed that the dorsal surface of L1 segment contains a higher density of locomotor rhythmic cells than the other segments. Moreover, L1 segment lesioning induced the most important changes in the locomotor activity in comparison with lesions at the T13 or L2 segments. However, no lesions led to selective disruption of either flexor or extensor output. In addition, this study found no evidence of functional parcellation of locomotor interneurons into flexor and extensor pools at the dorsal-ventral midline of the lumbar spinal cord of the rat