Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is a series of severe genetic conditions affecting skin and nails caused by mutations in the COL7A1 gene. DEB has a strong phenotypic variability. In the present study, we recruited a case with a boy exhibiting typical DEB indication, and performed a clinical, genetic, and experimental investigation, followed by a prenatal diagnosis on their current pregnancy. Whole exome sequencing identified a novel compound heterozygous variation in COL7A1, consisting of two variants, namely c.191T>C (p.Leu64Pro) and c.5124G>A (p.Leu1708=) in the proband. In vitro study by minigene system indicated that c.5124G>A would result in an increased ratio of a transcript with exon-skipping, which supported its pathogenicity. Further prenatal detection confirmed the genotype-phenotye co-separation in this family. In conclusion, the findings in our study expanded the mutation spectrum of DEB, and emphasized the importance of paying attention to specific synonymous variants in the filtering process.

Electron Trapping from Interactions between Laser-Driven Relativistic Plasma Waves.

Interactions of large-amplitude relativistic plasma waves were investigated experimentally by propagating two synchronized ultraintense femtosecond laser pulses in plasma at oblique crossing angles to each other. The electrostatic and electromagnetic fields of the colliding waves acted to preaccelerate and trap electrons via previously predicted, but untested injection mechanisms of ponderomotive drift and wake-wake interference. High-quality energetic electron beams were produced, also revealing valuable new information about plasma-wave dynamics.

Preliminary Evaluation of Virtual Touch Tissue Imaging Quantification for Differential Diagnosis of Metastatic and Nonmetastatic Cervical Lymph Nodes.

OBJECTIVES: Virtual Touch tissue imaging quantification (VTIQ; Siemens Medical Solutions, Mountain View, CA) is useful for assessing tissue hardness. This study aimed to investigate the value of VTIQ in differential diagnosis of cervical lymph nodes. METHODS: We retrospectively analyzed conventional sonograms and VTIQ images of 85 pathologically confirmed patients with superficial lymph node lesions. Conventional sonography was first performed, with 2-dimensional images described. Then VTIQ shear wave velocity (SWV) values of superficial lymph nodes were measured. With pathologic diagnosis as the reference standard, a receiver operating characteristic curve was generated to evaluate VTIQ efficacy in differential diagnosis of metastatic and nonmetastatic cervical lymph nodes. RESULTS: Of the 85 nodes, 44 and 41 were metastatic and nonmetastatic, respectively. The latter group included 24 and 17 hematologic/lymphatic system disease and reactive hyperplastic nodes, respectively. Shear wave velocity values of metastatic nodes were significantly higher than those of their nonmetastatic counterparts (P < .001). With an area under the curve (AUC) of 0.953 and SWV cutoff of 3.27 m/s, accuracy, sensitivity, and specificity were 89.4%, 88.6%, and 90.2%, respectively, for distinguishing metastatic and nonmetastatic nodes. An AUC of 0.943 and SWV cutoff of 3.23 m/s yielded accuracy, sensitivity, and specificity of 88.2%, 88.6%, and 87.5% for differentiating metastatic from hematologic/lymphatic system disease nodes. Finally, an AUC of 0.968 and SWV cutoff of 3.27 m/s yielded accuracy, sensitivity, and specificity of 90.2%, 88.6%, and 94.1% for differentiating metastatic from reactive hyperplastic nodes. CONCLUSIONS: Virtual Touch tissue imaging quantification is efficient in differential diagnosis of metastatic and nonmetastatic cervical lymph nodes.

Wavefront-correction for nearly diffraction-limited focusing of dual-color laser beams to high intensities.

We demonstrate wavefront correction of terawatt-peak-power laser beams at two distinct and well-separated wavelengths. Simultaneous near diffraction-limited focusability is achieved for both the fundamental (800 nm) and second harmonic (400 nm) of Ti:sapphire-amplified laser light. By comparing the relative effectiveness of various correction loops, the optimal ones are found. Simultaneous correction of both beams of different color relies on the linear proportionality between their wavefront aberrations. This method can enable two-color experiments at relativistic intensities.

Generation of 9 MeV γ-rays by all-laser-driven Compton scattering with second-harmonic laser light.

Gamma-ray photons with energy >9 MeV were produced when second-harmonic-generated laser light (3 eV) inverse-Compton-scattered from a counterpropagating relativistic (~450 MeV) laser-wakefield-accelerated electron beam. Two laser pulses from the same laser system were used: one to accelerate electrons and one to scatter. Since the two pulses play very different roles in the γ-ray generation process, and thus have different requirements, a novel laser system was developed. It separately and independently optimized the optical properties of the two pulses. This approach also mitigated the deleterious effects on beam focusing that generally accompany nonlinear optics at high peak-power levels.

Adaptive-feedback spectral-phase control for interactions with transform-limited ultrashort high-power laser pulses.

Fourier-transform-limited light pulses were obtained at the laser-plasma interaction point of a 100-TW peak-power laser in vacuum. The spectral-phase distortion induced by the dispersion mismatching between the stretcher, compressor, and dispersive materials was fully compensated for by means of an adaptive closed-loop. The coherent temporal contrast on the sub-picosecond time scale was two orders of magnitude higher than that without adaptive control. This novel phase control capability enabled the experimental study of the dependence of laser wakefield acceleration on the spectral phase of intense laser light.

Subcycle ac stark shift of helium excited states probed with isolated attosecond pulses.

Recent advances in attosecond science have relied upon the nearly instantaneous response of free electrons to an external field. However, it is still not clear whether bound electrons are able to rearrange on sublaser cycle time scales. Here, we probe the optical Stark shifts induced by a few-cycle near infrared laser field in helium bound states using isolated attosecond pulses in a transient absorption scheme and uncover a subcycle laser-induced energy level shift of the laser-dressed 1s3p state.

Contrast-enhanced ultrasound with SonoVue could accurately assess the renal microvascular perfusion in diabetic kidney damage.

OBJECTIVE: The aim of this study was to investigate the clinical significance of real-time gray-scale contrast-enhanced ultrasound (CEUS) through evaluating renal microvascular perfusion in diabetic kidney damage. METHODS: Diabetic patients (aged: 62.5±7.2, n=33) were divided into Group A with chronic kidney disease (CKD) Stages I and II (n=19) and Group B (n=14) with CKD Stages IV and V. Twenty-one healthy adults were selected as control group. The real-time and dynamic imaging from renal cortex was performed using contrast-enhanced ultrasound with SonoVue. The outage time-intensity curves (TICs) with >85% goodness-of-fit index were chosen for the analysis of basic intensity, intensity increment (A1), arriving time (AT), time to peak (TTP), mean transit time, peak intensity (PI) and total area under the curve (AUC). RESULTS: (i) After intravenous injection of a contrast agent, the renal artery, cortex, pyramid and renal vein were clearly displayed in sequence. (ii) TIC of renal cortical Perfusion in all groups showed an asymmetrical single-peak curve, which has an obvious ascending slope, peak and descending slope. The ascending slope was steep, whereas the descending slope was flat. However, the ascending slope in Group A and B was flatter than that in the control group. (iii) Compared to the control group, AT and TTP were all markedly prolonged but A1 and PI were significantly decreased in Group A and B (P<0.05). In Group A, the AUC had a trend of increase; however, the area under the ascending slope (AUC1), area under the descending slope (AUC2) and AUC were all decreased in Group B (P<0.05). (iv) AUC positively correlated with glomerular filtration rate (GFR) (r=0.472, P=0.01), but TTP did not correlate well with GFR (r=0.262, P=0.177). CONCLUSIONS: CEUS could accurately assess renal microvascular perfusion in a real-time and dynamic manner. PI, TTP and AUC could be used for the diagnosis of the renal microvascular damage in early and late stage diabetic patients. CEUS is a safe, noninvasive and simple technique to detect the severity of kidney microvascular perfusion deficits.

Vascular effects of microbubble-enhanced, pulsed, focused ultrasound on liver blood perfusion.

The purpose of this study was to investigate the vascular effects of microbubble-enhanced pulsed high-pressure ultrasound on liver blood perfusion. In the presence of circulating lipid-shell microbubbles, a focused ultrasound transducer was used to transcutaneously treat eight livers of healthy rabbits for perfusion analysis and to treat three livers with the abdomen open for histologic analysis. Twenty-two livers treated with the ultrasound only (n = 11) or microbubbles only (n = 11) served as the controls. The focused ultrasound was operated at a frequency of 1.22 MHz with a peak negative pressure of 4.6 MPa. The liver blood perfusion was estimated by performing contrast-enhanced ultrasound and gray-scale quantification on the livers before and after treatment. A temporary, nonenhanced region occurred in all of the experimental livers. The regional contrast gray-scale values of the experimental group dropped significantly from 88.4 before treatment to 2.7 after treatment. The liver perfusion also demonstrated a gradual recovery over a 60-min period. The liver perfusion of the control groups remained the same after treatment. We found microvascular rupture, hemorrhage and swelling hepatocytes upon histologic examination of the experimental group. Regional liver blood perfusion can be temporarily blocked by microbubble-enhanced focused ultrasound with high-pressure amplitude. These vascular effects can be explained as acute microvascular injury of the liver and may have clinical implications.

Intravenous umbilical cord mesenchymal stem cell infusion for the treatment of combined malnutrition nonunion of the humerus and radial nerve injury.

Nonunion and nerve injury are the most severe and common complications of bone fracture treatments. There is still no ideal therapy for these two complications. In this report, we first applied umbilical cord mesenchymal stem cell (UC-MSC) therapy to one patient with both nonunion and nerve injury, and observed the therapeutic effects. UC-MSCs were produced and expanded according to a clinical-grade technique using serum-free medium enriched in human platelet lysate. Flow cytometry was performed to evaluate the purity of UC-MSCs, which were then intravenously injected. At 60 days postinjection, clinical examinations were performed to evaluate the therapeutic effects. Compared with before treatment, the patient's nerve reflex was present, and their muscle tone and strength increased, and x-ray and electromyography analysis further showed that the fracture gap disappeared and the nerve conduction velocity increased with shorter latency and higher amplitude. Furthermore, the clinical evolution was favorable and no side effects were observed during the 1-year follow-up. Overall, this novel treatment might open up a new strategy for the treatment of bone fracture complications.

Usefulness of enhanced power Doppler imaging in monitoring acral microcirculation in type 2 diabetes mellitus and its complications.

This study compared hemodynamic changes of acral arterioles (pulps and nail beds of fingers and toes) and the microcirculatory status of acra between patients with uncomplicated (n = 45) or complicated (n = 36) type 2 diabetic mellitus (type 2 DM) and healthy subjects (n = 40). Enhanced power Doppler imaging (e-Flow) was used to display the nail bed arterioles and distal branches of pulp arterioles (digitales palmares propriea and digitales plantares propriea) in the end knuckle of the right middle finger and right big toe. Arteriolar density (AD) was assessed by vascular pixel percentage. Compared to healthy subjects, in patients with DM the end diastolic velocity (EDV) of the nail bed arterioles of both finger and toe was diminished, while the vascular resistance index (RI) was increased. These changes became more prominent with a longer duration of the disease. Furthermore, both the peak systolic velocity (PSV) and AD were decreased in patients with DM. These hemodynamic changes were also evident in the pulp arterioles of fingers and toes, although they appeared at more advanced stages of the disease. Overall, the abnormal changes were more pronounced in patients with complications. In conclusion, hemodynamic changes (e.g. decrease in the number of acral arterioles) progress with a longer duration of the disease. The acral arteriolar damage is more pronounced in patients with a complicated type 2 DM.

[Distribution, flux and photoproduction of carbon monoxide in the Yellow Sea and the Bohai Sea in spring].

Concentration distribution, sea-to-air flux, photoproduction of carbon monoxide (CO) in the surface seawater and atmospheric CO mixing ratio were measured in the Yellow Sea and the Bohai Sea. A headspace analysis system was used for CO measurement. The concentrations of CO in the surface seawater ranged from 0.19 to 3.57 nmol x L(-1), with an average of 1.24 nmol x L(-1) ( SD = 0.79, n = 69). Overall, the concentrations of CO displayed a decreasing trend from the coast to the offshore stations and followed diurnal variations after classifying and averaging the CO concentrations according to sampling and analysing time in the unit of one hour, with the maximum values in midnoon which was 10 folds higher than the minimum values in predawn. Atmospheric CO mixing ratios varied from 215 x 10(-9) to 850 x 10(-9), with an average of 414 x 10(-9) (SD = 140 x 10(-9), n = 69), due to obvious terrestrial input. The supersaturation factors of CO varied from 0.42-18.90, with an average of 3.61 (SD = 2.99, n = 69), indicating that the Yellow Sea and the Bohai Sea was a net source of atmospheric CO. The average sea-to-air fluxes of CO from the Yellow Sea and the Bohai Sea were estimated to be (1.22 +/- 1.70) micromol x (m2 x d)(-1) by the LM86 equation and (2.13 +/- 2.91) micromol x (m2 x d)(-1) by the W92 equation, respectively. Using SMARTS2 spectral irradiance model to estimate CO production, the photoproduction rate of CO was 54.60 micromol x (m2 x d)(-1) and the photoproduction of carbon in the Yellow Sea and the Bohai Sea was 26.95 x 10(9) g in spring. The photoproduction rate of CO was 25-50 times higher than the sea-to-air flux, suggesting that most part of CO was removed by microbial process in the surface seawater.

Sub-15fs ultraviolet pulses generated by achromatic phase-matching sum-frequency mixing.

A broadband ultraviolet pulse with a spectral width of 44 nm was generated by achromatic sum-frequency mixing of an 805-nm pulse and ultrabroadband visible pulse. Angular dispersion was introduced to achieve broadband phase matching by a prism pair. The UV pulse was compressed to 13.2 fs with another prism pair, with energy of 600 nJ.

Ultrabroadband noncollinear optical parametric amplification with LBO crystal.

Ultrabroadband visible noncollinear optical parametric amplification (NOPA) was achieved in an LBO crystal, with a continuum seed pulse generated from a sapphire plate. The spectral bandwidth of the amplified visible pulse was about 200 nm, which can support sub-5 fs pulse amplification. An amplified output of 0.21 microJ with an average gain of about 210 was achieved. This provides, to the best of our knowledge, the first-time demonstration of such broadband amplification with a biaxial nonlinear optical crystal. Both the simulation and experimental results indicate that the LBO has a great potential as nonlinear medium in power amplifier for TW to PW noncollinear optical parametric chirped pulse amplification (NOPCPA) systems.

Comparison of contrast enhanced ultrasound and contrast enhanced CT or MRI in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma: a multi-center study in China.

To evaluate the ability of contrast enhanced ultrasound (CEUS) in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma (HCC) in comparison with contrast enhanced computed tomography (CECT) and/or magnetic resonance imaging (CEMRI). A total of 151 patients were enrolled in the study. Before the radio-frequency (RF) or microwave ablation treatment, tumor vascularity was assessed in 139 patients with three imaging modalities i.e., US (139 exams), CEUS (139 exams) and CECT (103 exams)/CEMR (36 exams). CEUS examination was performed using a sulphur hexafluoride-filled microbubble contrast agent (SonoVue((R)), Bracco, Milan, Italy) and real-time contrast-specific imaging techniques. Within 30 +/- 7 d after the ablation procedure, 118/139 patients were monitored to assess the tumor response to treatment. Before ablation, contrast enhancement within tumor was observed in 129/139 (92.8%) patients with CEUS and 133/139 (95.7%) patients with CECT/CEMRI. Compared with CECT/CEMRI, CEUS sensitivity and accuracy in detecting tumor vascularity were 97.0% and 94.2%, respectively. One month after treatment, no enhancement was seen in 110/118 (93.2%) both on CEUS and CECT/CEMRI. Concordance between CEUS and CECT/CEMR on the presence of residual vascularization was obtained in four patients (true positive). The specificity and accuracy of CEUS in detecting tumor vascularity were 98.2% and 96.6%, respectively. The periprocedural impact of SonoVue administration on the assessment of treatment extent was also evaluated in a subgroup of patients and CEUS showed its superiority compared with baseline US in defining treatment outcome. In conclusion, in the detection of HCC tumor vascularity and assessment of response to thermal ablation after 1 month, real time CEUS provided results comparable to those obtained with CECT/CEMRI. CEUS examination proved to be a safe and easy to access procedure, with potential for diagnostic impact in the clinical practice.

Parasitic lasing suppression in high gain femtosecond petawatt Ti:sapphire amplifier.

New parasitic lasing suppression techniques are developed and high gain amplification is demonstrated in a petawatt level Ti:sapphire amplifier based on the chirped pulse amplification (CPA) scheme. Cladding the large aperture Ti:sapphire with refractive-index matched liquid doped with absorber suppresses the transverse lasing. The acousto-optic programmable dispersive filter (AOPDF) is used to realize side-lobe suppression in the temporal profile of the compressed pulse. The 800 nm laser output with peak power of 0.89 PW and pulse width of 29.0 fs is demonstrated.

Transplantation of angiogenin-overexpressing mesenchymal stem cells synergistically augments cardiac function in a porcine model of chronic ischemia.

OBJECTIVE: Accumulated evidence suggests that myogenesis and angiogenesis induced by implanted cells play important roles in restoring cardiac function after a myocardial infarction. The current study investigated the effects of transplanted autologous mesenchymal stem cells overexpressing angiogenin on myocardial perfusion and cardiac function in the porcine chronic ischemic model. METHODS: Chronic ischemia was generated in Yorkshire pigs by placing an ameroid constrictor around the left circumflex artery. Four weeks after occlusion, the animals were randomly separated into 4 groups: pigs in the MSC(AdAng) or MSC(AdNull) groups were implanted with 6 x 10(8) mesenchymal stem cells infected with adenovirus containing angiogenin gene or null adenovirus, respectively; pigs in the AdAng or AdNull groups were injected intramyocardially with adenovirus (5 x 10(9) plaque forming unit/pig) containing angiogenin gene or null adenovirus, respectively. Four weeks after implantation, mesenchymal stem cells prelabeled with DiI were observed within the implanted area in both cell transplantation groups. RESULTS: Angiogenin protein levels were significantly greater in the MSC(AdAng) and AdAng groups than in the other 2 groups and were associated with greater neovessel formation than in the other 2 groups. Mesenchymal stem cell transplantation decreased scar size and increased scar thickness. Both the AdAng and MSC(AdNull) groups experienced improved cardiac function compared with that seen in the AdNull group. However, a synergistic effect of mesenchymal stem cells and angiogenin was observed in the MSC(AdAng) group because myocardial perfusion and cardiac function increased significantly (P < .05 for all groups) in this group compared with all the others. CONCLUSIONS: Transplantation of autologous mesenchymal stem cells transfected with the angiogenin gene revealed a synergistic effect on the improvement of heart perfusion and function after ameroid occlusion.

Experimental study of acute organophosphorus compound poisoning in rabbit kidneys by ultrasonic tissue characterization.

OBJECTIVE: The purpose of this study was to investigate the value of integrated backscatter (IBS) of kidneys in acute organophosphorus compound poisoning in rabbits. METHODS: Eighteen rabbits were poisoned by dimethyl dichlorovinyl phosphate to establish animal models. Sonographic examinations were performed before (T0) and after (T1-T9) the rabbits were poisoned. The echo and size of kidneys were evaluated by 2-dimensional gray scale sonography. Changes of the renal cortex and medulla were analyzed quantitatively with IBS. RESULTS: No change of the cortex echo was found before and after poisoning. A significant change of the volume of kidneys on both sides began at T6 compared with that at T0 (P < .05). A significant change of renal length on both sides began at T7 compared with that at T0 (P < .05). The volume change was earlier than that of length. A significant change in IBS% of the renal cortex began at T5 compared with that at T0 (P < .05), whereas a significant change in IBS% of the renal medulla began at T6 compared with that at T(0) (P < .05). The change in IBS% of the renal cortex was earlier. CONCLUSIONS: More useful information provided by IBS% has been found in acute organophosphorus compound poisoning in rabbits.

Degenerated optical parametric chirped-pulse amplification with cesium lithium borate.

A gain amplifier for degenerated optical parametric chirped-pulse amplification (OPCPA) with lithium triborate and cesium lithium borate (CLBO) crystals was demonstrated in a near-collinear configuration. The signal gain of the final energy amplifier with CLBO was approximately 6. After compression, the 123 fs pulse duration was obtained. Compared with potassium dihydrogen phosphate, it is confirmed that CLBO is more effective as a nonlinear crystal in a final power amplifier for terawatt or petawatt OPCPA systems. To our knowledge, this is the first demonstration of OPCPA with CLBO.