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Virological breakthrough is a clinical manifestation in patients infected with chronic hepatitis B (CHB), who undergo treatment with nucleoside/nucleotide analogs (NUCs). The current understanding of the underlying mechanism of virological breakthrough is limited. Ultra‑deep pyrosequencing (UDPS) is a novel and powerful tool used to investigate minor viral variants and viral evolution. The present study used UDPS to investigate the viral evolution pattern during virological breakthrough in patients with CHB treated with NUCs. A total of 12 patients who experienced virological breakthrough were recruited in the present study. During the treatment with lamivudine, adefovir was added as a rescue therapy when virological breakthrough emerged, and the therapy was continued until week 96. Serum samples from each patient were collected at different time points for UDPS analysis. Treatment with lamivudine resulted in an increased rate of the viral mutations, rtM204V/I, rtL180M and rtL80I. Virological breakthrough was accompanied by significant rtM204I/V substitutions in eight of the patients. A total of three types of rt204 mutation, associated with virological breakthrough, were observed, including YIDD variant‑dominated, YVDD variant‑dominated and YMDD wild‑type‑dominated virological breakthrough. YVDD variants reverted to the wild‑type following the adefovir add‑on rescue therapy, although the YIDD variants remained dominant following the combination therapy. The mechanism underlying virological breakthrough was revealed to be complex and associated with the rapid replication of mutated variants. UDPS analysis, therefore, provided a useful tool to investigate the dynamic evolution pattern of hepatitis B virus.

Objective: The aim of this article was to assess the catalytic activities of 24 cytochrome P450 2D6 (CYP2D6) variants found in the Chinese population toward atomoxetine in vitro as well as CYP2D6.1., Methods: In this study, the co-expression enzyme of human recombinant CYPOR, CYPb5, and CYP2D6.1 or other CYP2D6 variants with the baculovirus-mediated insect cells (Sf21) was used to study the catalytic activities of 24 CYP2D6 variants toward atomoxetine metabolism. The metabolite of atomoxetine (4-hydroxyatomoxetine) was detected by ultra-high performance liquid chromatography-mass spectrometry method., Results: The intrinsic clearance (Vmax/Km) values of most variants were significantly altered when compared with CYP2D6.1. CYP2D6.94, CYP2D6.D336N, CYP2D6.R440C exhibited marked increased values 172, 126, 121% respectively. CYP2D6.89 and CYP2D6.98 exhibited similar catalytic activity as the wild type, whereas 17 variants exhibited significantly decreased values (from 5 to 87%) due to increase Km and/or decrease Vmax values. However, CYP2D6.92 and CYP2D6.96 showed no or few activity because of producing nothing., Conclusions: Our results suggest that most of these newly found variants exhibit significantly changed catalytic activities compared with the wild type. And these findings provide valuable information for the growth and development of personalized medicine in China., (© 2015 S. Karger AG, Basel.)

We are currently in the midst of a worldwide obesity epidemic, including in patients with end-stage kidney disease. Placing hemodialysis catheters is a particular challenge in patients with extreme obesity. Here we describe the merging of two technologies to place catheters in patients who are too heavy (over 225 kg) to be placed safely on a procedure table for fluoroscopic guidance. The first technology is ECG-guided placement of catheters, well established for guidance of peripherally inserted central catheters (PICCs) and tunneled and nontunneled central venous catheters. The second is reverse-tunneling dialysis catheters, which allow precise placement of the tip of the catheter before creating the tunnel. We successfully placed catheters in three morbidly obese patients with acute kidney injury and followed them until their kidneys recovered and the catheters were removed. The catheters were placed in the patient's bed in a procedure room with subsequent confirmatory chest radiographs. Catheter performance based on blood flow rates was excellent and there were no complications. We suggest placement of ECG-guided tunneled hemodialysis catheters using a reversed-tunneling technique in those patients with extreme obesity who are too heavy to place on a fluoroscopy procedure table.

Different size InGaN/GaN based micro-LEDs (μLEDs) are fabricated. An extremely high injection level above 16 kA/cm2 is achieved for 10 μm-diameter LED. The lateral current density and carrier distributions of the μLEDs are simulated by APSYS software. Streak camera time resolved photoluminescence (TRPL) results show clear evidence that the band-gap renormalization (BGR) effect is weakened by strain relaxation in smaller size μLEDs. BGR affects the relaxation of free carriers on the conduction band bottom in multiple quantum wells (MQWs), and then indirectly affects the recombination rate of carriers. An energy band model based on BGR effect is made to explain the high-injection-level phenomenon for μLEDs.

Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Optogenetics has proven to be a revolutionary technology in neuroscience and has advanced continuously over the past decade. However, optical stimulation technologies for in vivo need to be developed to match the advances in genetics and biochemistry that have driven this field. In particular, conventional approaches for in vivo optical illumination have a limitation on the achievable spatio-temporal resolution. Here we utilize a sapphire-based microscale gallium nitride light-emitting diode (μLED) probe to activate neocortical neurons in vivo. The probes were designed to contain independently controllable multiple μLEDs, emitting at 450 nm wavelength with an irradiance of up to 2 W/mm(2). Monte-Carlo stimulations predicted that optical stimulation using a μLED can modulate neural activity within a localized region. To validate this prediction, we tested this probe in the mouse neocortex that expressed channelrhodopsin-2 (ChR2) and compared the results with optical stimulation through a fiber at the cortical surface. We confirmed that both approaches reliably induced action potentials in cortical neurons and that the μLED probe evoked strong responses in deep neurons. Due to the possibility to integrate many optical stimulation sites onto a single shank, the μLED probe is thus a promising approach to control neurons locally in vivo.

Objective: The aim of this study was to compare the effects of anesthesia by dexmedetomidine and propofol on the hemodynamics and oxygen balance in children with complex congenital heart disease who were undergoing cardiac surgery., Methods: Fifty-seven children were randomized to receive either a continuous infusion of propofol (6-8 mg/kg/h) or dexmedetomidine (0.5-0.7 μg/kg/h) after anesthesia induction. Hemodynamic data were recorded. Oxygen balance parameters were assessed at baseline after midazolam sedation, before and immediately after skin incisions were made, after sternotomy, 5 minutes after protamine administration, and at the end of surgery., Results: Compared with the dexmedetomidine group, the propofol group exhibited decreases in blood pressure, cardiac output, and cardiac index before skin incision (P < .05) and increases in blood pressure, heart rate, cardiac output, and cardiac index after sternotomy (P < .01). However, very similar trends in oxygen dynamics were obtained in both groups (P > .05), and the cardiac index was not correlated with total oxygen consumption (r = -0.109, P = .066) or the oxygen extraction ratio (r = -0.107, P = .072)., Conclusions: Dexmedetomidine infusion may be superior to propofol anesthesia in children with complex congenital heart disease who are undergoing cardiopulmonary bypass because dexmedetomidine was associated with less variability in heart rate or blood pressure during surgery. However, the oxygen balance was similar when either agent was used., (© 2014 Wiley Periodicals, Inc.)

We report the transfer printing of blue-emitting micron-scale light-emitting diodes (micro-LEDs) onto fused silica and diamond substrates without the use of intermediary adhesion layers. A consistent Van der Waals bond was achieved via liquid capillary action, despite curvature of the LED membranes following release from their native silicon growth substrates. The excellence of diamond as a heat-spreader allowed the printed membrane LEDs to achieve optical power output density of 10 W/cm(2) when operated at a current density of 254 A/cm(2). This high-current-density operation enabled optical data transmission from the LEDs at 400 Mbit/s.

A monolithic diamond Raman laser is reported. It utilizes a 13-mm radius of curvature lens etched onto the diamond surface and dielectric mirror coatings to form a stable resonator. The performance is compared to that of a monolithic diamond Raman laser operating in a plane-plane cavity. On pumping with a compact Q-switched laser at 532 nm (16 μJ pulse energy; 1.5 ns pulse duration; 10 kHz repetition-rate; M 2 <1.5), laser action was observed at the first, second, and third Stokes wavelengths (573 nm, 620 nm and 676 nm, respectively) in both cases. For the microlens cavity, a conversion efficiency of 84% was achieved from the pump to the total Raman output power, with a slope efficiency of 88%. This compares to a conversion efficiency of 59% and a slope efficiency of 74% for the plane-plane case. Total Raman output powers of 134 and 96 mW were achieved for the microlens and plane-plane cavities, respectively.

Objectives: The objective of the present meta-analysis was to investigate whether the combined evidence shows an association between the STAT4 rs7574865 polymorphism and RA., Methods: A systematic search of all relevant studies published through April 2013 was conducted using MEDLINE, EMBASE, OVID, and ScienceDirect. The observational studies that were related to an association between the STAT4 rs7574865 polymorphism and RA were identified. The association between the STAT4 rs7574865 polymorphism and RA susceptibility was assessed using genetic models., Results: Seventeen case-control studies with a total of 28 comparisons (25 300 RA patients and 26 326 controls) met the inclusion criteria. A meta-analysis was conducted for genotype TT versus GT+GG, GT+TT versus GG, TT versus GG and T-allele. The meta-analysis showed an association between RA and the STAT4 rs7574865 TT genotype, GT+TT genotype and T-allele in all subjects. Stratification of RA patients according to ethnic group showed that the TT genotype, GT+TT genotype and T-allele were significantly associated with RA in Europeans, Asians, Africans and Latin Americans. A subgroup analysis according to the absence or presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between the STAT4 rs7574865 polymorphism and RA may be independent of the presence of RF and anti-CCP antibodies., Conclusions: This meta-analysis demonstrated that the STAT4 rs7574865 polymorphism confers susceptibility to RA in major ethnic groups. The association may not be dependent on the presence of RF and anti-CCP antibodies., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

A rapid-resolution ultra high-performance liquid chromatography-tandem mass spectrometry separation method (UPLC-MS/MS) was developed for the simultaneous determination of carvedilol, and its three metabolites: 4'-hydroxyphenyl-carvedilol, 5'-hydroxyphenyl-carvedilol, o-desmethyl-carvedilol. The effective UPLC-MS/MS separation of the examined compounds was applied on an Acquity BEH C18 column (2.1 mm × 5 0 mm, 1.7 μm particle size) column with a gradient mobile phase system. The analysis was performed in less than 6 min with a flow rate of 0.4 mL/min. The assay was validated over concentration ranges of 0.500-100 ng/mL for carvedilol and 0.0500-10.0 ng/mL for its three metabolites. Intra- and inter-assay precision values for replicate quality control samples were within 11.4% for all analytes during the assay validation. Mean quality control accuracy values were within ±11.5% of nominal values for all analytes. Assay recoveries were high (>91%) and internal standard normalized matrix effects were minimal. The four analytes were stable in rat plasma for at least 24h at room temperature, 89 days at -20 °C and -80 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of carvedilol and its pharmacologically active metabolites in rat pharmacokinetic study. The accurate and simple method we developed could be applied to human pharmacokinetic study in the near future., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: This study investigated the effects of aortic root infusion of sufentanil on myocardial ischemia/reperfusion injury in patients undergoing elective mitral valve replacement (MVR) with cardiopulmonary bypass (CPB)., Design: A prospective, randomized, clinical study., Setting: A university-affiliated teaching hospital., Participants: Fifty-three adult patients undergoing elective MVR with CPB., Interventions: Bolus infusions of sufentanil (0.2 μg/kg, n = 24) or normal saline (n = 29) were administered through the aortic root cardioplegia perfusion catheter 5 minutes before aortic unclamping., Measurements and Main Results: Plasma concentrations of CK-MB and cTnI and variables including heart rate, mean arterial pressure, central venous pressure, cardiac output, stroke volume, duration of mechanical ventilation, length of ICU stay, length of hospital stay, and 24-hour postoperative inotropic scores were recorded. Plasma concentrations of CK-MB and cTnI were significantly lower 4 and 8 hours after aortic unclamping in the sufentanil postconditioning group compared to control (p<0.05). Inotropic drug use, duration of mechanical ventilation, and length of ICU and hospital stays were reduced significantly in the sufentanil postconditioning group compared to control (p< 0.05)., Conclusions: The present study demonstrated that sufentanil can attenuate myocardial ischemia-reperfusion injury in patients undergoing elective MVR with CPB., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A compact optoelectronic tweezers system for combined cell manipulation and analysis is presented. CMOS-controlled gallium nitride micro-LED arrays are used to provide simultaneous spatio-temporal control of dielectrophoresis traps within an optoelectronic tweezers device and fluorescence imaging of contrasting dye labelled cells. This capability provides direct identification, selection and controlled interaction of single T-lymphocytes and dendritic cells. The trap strength and profile for two emission wavelengths of micro-LED array have been measured and a maximum trapping force of 13.1 and 7.6 pN was achieved for projected micro-LED devices emitting at λmax 520 and 450 nm, respectively. A potential application in biological research is demonstrated through the controlled interaction of live immune cells where there is potential for this method of OET to be implemented as a compact device.

Background: The output of the neuronal digital spikes is fulfilled by axonal propagation and synaptic transmission to influence postsynaptic cells. Similar to synaptic transmission, spike propagation on the axon is not secure, especially in cerebellar Purkinje cells whose spiking rate is high. The characteristics, mechanisms and physiological impacts of propagation deceleration and infidelity remain elusive. The spike propagation is presumably initiated by local currents that raise membrane potential to the threshold of activating voltage-gated sodium channels (VGSC)., Results: We have investigated the natures of spike propagation and the role of VGSCs in this process by recording spikes simultaneously on the somata and axonal terminals of Purkinje cells in cerebellar slices. The velocity and fidelity of spike propagation decreased during long-lasting spikes, to which the velocity change was more sensitive than fidelity change. These time-dependent deceleration and infidelity of spike propagation were improved by facilitating axonal VGSC reactivation, and worsen by intensifying VGSC inactivation., Conclusion: Our studies indicate that the functional status of axonal VGSCs is essential to influencing the velocity and fidelity of spike propagation.

Background: Children with obstructive sleep apnea (OSA) are particularly at risk under anesthesia after uvulopalatopharyngoplasty (UPPP). This prospective randomized double-blind study focused on the comparison of dexmedetomidine-ketamine and sevoflurane-sufentanil anesthesia on children with respect to safety, feasibility, and clinical effects., Materials and Methods: A total of 60 children, aged 2-10 years, classified as American Society of Anesthesiologists (ASA) status I and II scheduled for UPPP were prospectively studied. Patients were randomly allocated to receive either dexmedetomidine-ketamine-based anesthesia (group DK, n = 30) or sevoflurane-sufentanil-based anesthesia (group SS, n = 3 0). Heart rate (HR) and systolic blood pressure during the first 60 min of the procedure, Ramsay sedation score, the Pediatric Anesthesia Emergence Delirium (PAED) scale and a 5-point scale used to evaluate emergence agitation (EA) in postanesthesia care unit (PACU) and postoperative outcomes data were recorded., Results: During the first 60 min of anesthesia, mean HR, and mean diastolic noninvasive arterial blood pressure (NIBP) were not statistically different in the two groups (P > 0.05) Compared with group SS, the patients in group DK had lower rescue tramadol requirement and lower pain score, PAED score, and EA score at 5, 10, 15, and 30 min in PACU; but had a higher Ramsay scale at 10, 15, 30, 45, and 60 min in PACU and the incidence of SpO2 below 95%, also the time of first bowel movement and ambulation in group DK was shorter., Conclusions: The dexmedetomidine-ketamine combination was not superior to a sevoflurane-sufentanil combination because of late awake time and a high potential for adverse respiratory events in PACU, the benefit of dexmedetomidine administration being a decreased incidence of EA and a lower recovery time of bowel movement and ambulation.

We present an optoelectrical device capable of in vitro optical stimulation and electrophysiological recording. The device consists of an array of micropixellated InGaN light-emitting diodes coupled to a custom-made ultrathin planar microelectrode array. Cells can be cultured directly on the chip for short- and long-term electrophysiological experiments. To show the functionality of the device, we transfected a cardiomyocyte-like cell line (HL-1) with a light-sensitive protein channelrhodopsin. We monitored action potentials of individual, spontaneously beating, HL-1 cells growing on the chip by extracellular electrical recordings. On-chip optical stimulation was demonstrated by triggering network activity in a confluent HL-1 cell culture and visualized by calcium imaging. We see the potential of our system for electrophysiological experiments with optogenetically modified cells. Optical stimulation can be performed directly on the chip without additional optical components or external light sources., (© 2013 Society of Photo-Optical Instrumentation Engineers (SPIE))

Background and Purpose: The use of iodinated contrast-enhanced imaging studies is increasing in acute cerebrovascular diseases, especially in subarachnoid hemorrhage (SAH). In SAH, such studies are essential for both diagnosis and treatment of the cause and sequela of hemorrhage. These patients are often subjected to multiple contrast studies such as computed tomographic angiography, computed tomographic perfusion, and cerebral angiography. They are also predisposed to intravascular volume depletion as a part of the disease process from cerebral salt wasting (CSW) and as a result of multiple contrast exposure can develop contrast-induced nephropathy (CIN). Data regarding CIN in this population are scarce. We aimed to examine the incidence of CIN in SAH and identify potential associative risk factors., Methods: We analyzed data from a prospectively collected patient database of patients with SAH admitted to the neurocritical intensive care unit in a single center over a period of 1 year. CIN was defined as an increase in serum creatinine by >1.5 times or >0.3 mg/dl greater than the admission value, or urine output <0.5 ml/kg/h during one 6-h block., Results: In this cohort of 75 patients with SAH who had undergone at least one contrast study, the mean age was 57.3 ± 15.6 years and 70.7% were women. Four percent developed CIN which resolved within 72 h and none required renal replacement therapy or dialysis. Patients older than 75 years (20%, p < 0.05), those with borderline renal function (14.3%, p = 0.26), diabetics (11.1%, p = 0.32), and those with lower recommended "maximum contrast dose" volume (33.3%, p = 0.12) had a trend toward development of CIN, although most were not statistically significant. Twenty-seven patients (36 %) were on 3% hypertonic saline (HTS) for CSW during the contrasted study but none developed CIN., Conclusions: The incidence of CIN in SAH patients is comparable to previously published reports on non-neurological cohorts. No definite association was noted with any predisposing factors postulated to be responsible for CIN, except for advanced age. Concurrent use of 3% HTS was not associated with CIN in this population.

Within optogenetics there is a need for compact light sources that are capable of delivering light with excellent spatial, temporal, and spectral resolution to deep brain structures. Here, we demonstrate a custom GaN-based LED probe for such applications and the electrical, optical, and thermal properties are analyzed. The output power density and emission spectrum were found to be suitable for stimulating channelrhodopsin-2, one of the most common light-sensitive proteins currently used in optogenetics. The LED device produced high light intensities, far in excess of those required to stimulate the light-sensitive proteins within the neurons. Thermal performance was also investigated, illustrating that a broad range of operating regimes in pulsed mode are accessible while keeping a minimum increase in temperature for the brain (0.5°C). This type of custom device represents a significant step forward for the optogenetics community, allowing multiple bright excitation sites along the length of a minimally invasive neural probe.

Wittichenite (Cu(3)BiS(3)) nanocrystals have been synthesized utilizing a hot-injection method. They have been characterized in detail. Cu(3)BiS(3) nanocrystals possessed a band gap of 1.56 eV, and the corresponding nanocrystal-film shows a clear photoresponse in I-V measurements. Our work illustrates that Cu(3)BiS(3) nanocrystals have potential in the application of solar cells.

Background: Lamivudine (LAM) and adefovir (ADV) are widely used in most Asian countries, though monotherapy is associated with the occurrence of resistance., Aim: To evaluate the efficiency of LAM and ADV combined treatment of chronic hepatitis B patients with compensated cirrhosis., Patients and Methods: 206 eligible Chinese patients were randomly assigned in a 1:1 ratio to receive either LAM or ADV for the first 24 weeks. According to virologic response at 24 weeks, the patients either continued to monotherapy or switched to combined therapy for 48 weeks. After 48 weeks, all patients received LAM and ADV combined therapy for 96 weeks., Results: Serum HBV DNA levels significantly decreased in patients with ADV or LAM monotherapy and continuously reduced after the combined therapy. Serum ALT normalized rate were 88.24% and 81.37% at week 48, and 95.74% and 87.36% at week 96 in ADV and LAM group respectively, comparing to 60.78% and 56.73% in ADV and LAM groups at baseline. The accumulated virological breakthrough rate at week 48 and 96 was significantly higher in LAM group., Conclusions: Both combination strategies were resulted in the long term virological, biochemical improvement in Chinese chronic hepatitis B patients with compensated cirrhosis.

Background: Sufentanil is widely used in clinical anaesthesia because of its protective effects against ischaemia/reperfusion injury. Diabetes mellitus elevates the activity of glycogen synthase kinase-3β (GSK-3β), thereby increasing the permeability of mitochondrial transition pore. This study investigated the role of GSK-3β in ameliorating the cardioprotective effect of sufentanil post-conditioning in diabetic rats., Methods: Streptozotocin-induced diabetic rats and age-matched non-diabetic rats were subjected to 30 min of ischaemia and 120 min of reperfusion. Five minutes before reperfusion, rats were administered one of the following: a vehicle, sufentanil (1 μg/kg), or a GSK-3β inhibitor SB216763 (0.6 mg/kg). Myocardial infarct size, cardiac troponin I, and the activity of GSK-3β were then assessed., Results: Sufentanil post-conditioning significantly reduced myocardial infarct size in the non-diabetic, but not in diabetic rats. SB216763 reduced infarct size in both diabetic and non-diabetic animals. Sufentanil-induced phospho-GSK-3β was reduced 5 min after reperfusion in diabetic rats, but not in non-diabetic rats., Conclusions: Sufentanil treatment was ineffective in preventing against ischaemia/reperfusion in diabetic rats, which is associated with the activation of GSK-3β. Our results also suggest that direct inhibition of GSK-3β may provide a strategy to protect diabetic hearts against ischaemia/reperfusion injury., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

In this work, an organic composite polymer random laser (RL) operating underwater has been studied. The RL structure used in the test is a rod-shaped composite, formed by a mixture of an organic green light-emitting polymer and a UV transparent polymer matrix. RL action was sustained by both the multiple scattering and whispering-gallery-mode effect. The demonstration of RL action and the test of its operation lifetime in such an organic composite RL operating in water suggest the feasibility of its promising future applications in areas of underwater optical communications and/or remote optical sensing.

Background: Studies in multiple organ systems have shown cross-talk between signaling through the bone morphogenetic protein receptor type 2 (BMPR2) and estrogen pathways. In humans, pulmonary arterial hypertension (PAH) has a female predominance, and is associated with decreased BMPR2 expression. The goal of this study was to determine if estrogens suppress BMPR2 expression., Methods: A variety of techniques were utilized across several model platforms to evaluate the relationship between estrogens and BMPR2 gene expression. We used quantitative RT-PCR, gel mobility shift, and luciferase activity assays in human samples, live mice, and cell culture., Results: BMPR2 expression is reduced in lymphocytes from female patients compared with male patients, and in whole lungs from female mice compared with male mice. There is an evolutionarily conserved estrogen receptor binding site in the BMPR2 promoter, which binds estrogen receptor by gel-shift assay. Increased exogenous estrogen decreases BMPR2 expression in cell culture, particularly when induced to proliferate. Transfection of increasing quantities of estrogen receptor alpha correlates strongly with decreasing expression of BMPR2., Conclusions: BMPR2 gene expression is reduced in females compared to males in live humans and in mice, likely through direct estrogen receptor alpha binding to the BMPR2 promoter. This reduced BMPR2 expression may contribute to the increased prevalence of PAH in females.

Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity.

Horse body size varies greatly due to intense selection within each breed. American Miniatures are less than one meter tall at the withers while Shires and Percherons can exceed two meters. The genetic basis for this variation is not known. We hypothesize that the breed population structure of the horse should simplify efforts to identify genes controlling size. In support of this, here we show with genome-wide association scans (GWAS) that genetic variation at just four loci can explain the great majority of horse size variation. Unlike humans, which are naturally reproducing and possess many genetic variants with weak effects on size, we show that horses, like other domestic mammals, carry just a small number of size loci with alleles of large effect. Furthermore, three of our horse size loci contain the LCORL, HMGA2 and ZFAT genes that have previously been found to control human height. The LCORL/NCAPG locus is also implicated in cattle growth and HMGA2 is associated with dog size. Extreme size diversification is a hallmark of domestication. Our results in the horse, complemented by the prior work in cattle and dog, serve to pinpoint those very few genes that have played major roles in the rapid evolution of size during domestication.

We demonstrate a single-step method for the generation of collagen and poly-l-Lysine (PLL) micropatterns on a poly(ethylene glycol) (PEG) functionalized glass surface for cell based assays. The method involves establishing a reliable silanization method to create an effective non-adhesive PEG layer on glass that inhibits cell attachment, followed by the spotting of collagen or PLL solutions using non-contact piezoelectric printing. We show for the first time that the spotted protein micropatterns remain stable on the PEG surface even after extensive washing, thus significantly simplifying protein pattern formation. We found that adherence and spreading of NIH-3T3 fibroblasts was confined to PLL and collagen areas of the micropatterns. In contrast, primary rat hepatocytes adhered and spread only on collagen micropatterns, where they formed uniform, well defined functionally active cell arrays. The differing affinity of hepatocytes and NIH-3T3 fibroblasts for collagen and PLL patterns was used to develop a simple technique for creating a co-culture of the two cell types. This has the potential to form structured arrays that mimic the in vivo hepatic environment and is easily integrated within a miniaturized analytical platform for developing high throughput toxicity analysis in vitro., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In this paper, the self-consistent solution of Schrödinger-Poisson equations was realized to estimate the radiative recombination coefficient and the lifetime of a single blue light InGaN/GaN quantum well (QW). The results revealed that the recombination rate was not in proportion to the total injected carriers, and thus the Bnp item was not an accurate method to analyze the recombination process. Carrier screening and band filling effects were also investigated, and an extended Shockley-Read-Hall coefficient A(kt) with a statistical weight factor due to the carrier distributions in real and phase space of the QW was proposed to estimate the total nonradative current loss including carrier nonradiative recombination, leakage and spillover to explain the efficiency droop behaviors. Without consideration of the Auger recombination, the blue shift of the electroluminescence spectrum, light output power and efficiency droop curves as a function of injected current were all investigated and compared with the experimental data of a high brightness blue light InGaN/GaN multiple QWs light emitting diode to confirm the reliability of our theoretical hypothesis.

Experimentally measured optical properties of photonic crystal LEDs are reported here. Photonic crystal and photonic quasi-crystal structures were fabricated on GaN epilayer LED wafer material using both direct-write electron beam lithography and nanoimprint lithography. Some of these structures were processed to make finished LEDs. Both electroluminescence and photoluminescence measurements were performed on these structures. Devices were characterized for their current-voltage characteristics, emission spectra, far-field emission pattern, and angular emission pattern. These results are useful for fabricating photonic crystal LEDs and assessing their operational properties.

We report random laser action in a system where optical amplification is provided by colloidal quantum dots (CQDs). This system is obtained by depositing from solution CdSe/ZnS core-shell CQDs into rough micron-scale grooves fabricated on the surface of a glass substrate. The combination of CQD random packing and of disordered structures in the glass groove enables gain and multiple scattering. Upon optical excitation, random laser action is triggered in the system above a 25-mJ/cm2 threshold. Single-shot spectra were recorded to study the emission spectral characteristics and the results show the stability of the laser mode positions and the dominance of the modes close to the material gain maximum.

A novel, miniaturized optoelectronic tweezers (OET) system has been developed using a CMOS-controlled GaN micro-pixelated light emitting diode (LED) array as an integrated micro-light source. The micro-LED array offers spatio-temporal and intensity control of the emission pattern, enabling the creation of reconfigurable virtual electrodes to achieve OET. In order to analyse the mechanism responsible for particle manipulation in this OET system, the average particle velocity, electrical field and forces applied to the particles were characterized and simulated. The capability of this miniaturized OET system for manipulating and trapping multiple particles including polystyrene beads and live cells has been successfully demonstrated.

Mechanically flexible distributed feedback (DFB) lasers are fabricated by a low-cost approach using soft-lithography from a holographic master grating. The gain material is a star-shaped oligofluorene providing laser emission from 425 to 442 nm with a soft pump threshold at 14.4 μJ/cm (2.7 kW/cm). Encapsulation of the devices enables stable operation in ambient atmosphere at a 1/e degradation energy dosage of 53 J/cm.

We report on an approach to ultraviolet (UV) photolithography and direct writing where both the exposure pattern and dose are determined by a complementary metal oxide semiconductor (CMOS) controlled micro-pixellated light emitting diode array. The 370 nm UV light from a demonstrator 8 x 8 gallium nitride micro-pixel LED is projected onto photoresist covered substrates using two back-to-back microscope objectives, allowing controlled demagnification. In the present setup, the system is capable of delivering up to 8.8 W/cm2 per imaged pixel in circular spots of diameter approximately 8 microm. We show example structures written in positive as well as in negative photoresist.

We report what we believe to be the first use of organic nanostructures for efficient colour conversion of gallium nitride light emitting diodes (LEDs). The particular nanomaterials, based on star-shaped truxene oligofluorenes, offer an attractive alternative to inorganic colloidal quantum dots in the search for novel and functional 'nanophosphors'. The truxenes have been formed into a composite with photoresist and ink-jet printed onto microstructured gallium nitride LEDs, resulting in a demonstrator hybrid microdisplay technology with pixel size approximately 32 microm. The output power density of the hybrid device was measured to be approximately 8.4 mW/cm(2) per pixel at driving current density of 870.8A/cm(2) and the efficiency of colour conversion at drive current of 7 mA was estimated to be approximately 50%.

We describe a CMOS-based micro-system for time-resolved fluorescence lifetime analysis. It comprises a 16 × 4 array of single-photon avalanche diodes (SPADs) fabricated in 0.35 μm high-voltage CMOS technology with in-pixel time-gated photon counting circuitry and a second device incorporating an 8 × 8 AlInGaN blue micro-pixellated light-emitting diode (micro-LED) array bump-bonded to an equivalent array of LED drivers realized in a standard low-voltage 0.35 μm CMOS technology, capable of producing excitation pulses with a width of 777 ps (FWHM). This system replaces instrumentation based on lasers, photomultiplier tubes, bulk optics and discrete electronics with a PC-based micro-system. Demonstrator lifetime measurements of colloidal quantum dot and Rhodamine samples are presented.

We report on the integration of monodisperse semiconductor nanocrystal (NC) color converters onto gallium nitride ultraviolet micro-pixelated light-emitting diodes ('micro-LEDs'). Integration is achieved in a 'self-aligned' process by forming a nanocomposite of the respective NCs in a photocurable epoxy polymer. Blue, green, yellow and red NC/epoxy blend microstructures have been successfully integrated onto micro-pixelated LEDs by this technique and utilised for color conversion, resulting in a five color emission single chip. Optical output power density of up to about 166 mW/cm2 is measured; spectral emission at 609 nm gives an estimated optical-to-optical conversion as high as 18.2% at 30 mA driving current.

We describe a simple implementation of a slit scanning confocal microscope to obtain an axial resolution better than that of a point-scanning confocal microscope. Under slit illumination, images of a fluorescent object are captured using an array detector instead of a line detector so that out-of-focus light is recorded and then subtracted from the adjacent images. Axial resolution after background subtraction is 2.2 times better than the slit confocal resolution, and out-of-focus image suppression is calculated to attenuate with defocus faster by 1 order of magnitude than in the point confocal case.

Micropixelated blue (470 nm) and ultraviolet (370 nm) AlInGaN light emitting diode ('micro-LED') arrays have been fabricated in flip-chip format with different pixel diameters (72 microm and 30 microm at, respectively, 100 and 278 pixels/mm(2)). Each micro-LED pixel can be individually-addressed and the devices possess a specially designed n-common contact incorporated to ensure uniform current injection and consequently uniform light emission across the array. The flip-chip micro-LEDs show, per pixel, high continuous output intensity of up to 0.55 microW/microm(2) (55 W/cm(2)) at an injection current density of 10 kA/cm(2) and can sustain continuous injection current densities of up to 12 kA/cm(2) before breakdown. We also demonstrate that nanosecond pulsed output operation of these devices with per pixel onaxis average peak intensity up to 2.9 microW/microm(2) (corresponding to energy of 45pJ per 22ns optical pulse) can be achieved. We investigate the pertinent performance characteristics of these arrays for micro-projection applications, including the prospect of integrated optical pumping of organic semiconductor lasers.

We report a tunable, single-mode vertical cavity surface-emitting laser (VCSEL) format suitable for array operation, power scaling, fiber coupling, and operation in isolated environments such as those required by atom optics. The devices are fiber VCSELs, consisting of a semiconductor gain and mirror structure separated from a mirror-coated optical fiber by an air (or vacuum) gap. The gain structure has polymer microlenses fabricated on its surface, of characteristics suitable to focus the oscillating mode on both cavity mirrors, ensuring stable fundamental mode emission and high fiber coupling efficiency. We demonstrate such devices in continuous-wave operation at 1.03 microm at room temperature, with a single-mode tuning range of 13 nm, laser threshold as low as 2.5 mW, and a maximum fiber-coupled output power of 10 mW.

Zinc tetraaminophthalocyanine-Fe3O4 nanoparticle composites were prepared by organic-inorganic complex technology and characterized. It has been proved that the ZnTAPc dispersed randomly onto the surface of Fe3O4 nanoparticles to form molecular dispersion layer and there was a relatively strong bond between central zinc cation and oxygen. The nanoparticle composite took the shape of roundish spheres with the mean diameter of about 15 nm. Active amino groups of magnetic carriers could be used to bind laccase via glutaraldehyde. The optimal pH for the activity of the immobilized laccases and free laccase were the same at pH 3.0 and the optimal temperature for laccase immobilization on ZnTAPc-Fe3O4 nanoparticle composite was 45 degrees. The immobilization yields and K(m) value of the laccase immobilized on ZnTAPc-Fe3O4 nanoparticle composite were 25% and 20.1 microM, respectively. This kind of immobilized laccase has good thermal, storage and operation stability, and could be used as the sensing biocomponent for the fiber optic biosensor based on enzyme catalysis.

Monoclinic NH(4)V(3)O(8) single-crystalline nanobelts with widths of 80-180 nm, thicknesses of 50-100 nm, and lengths up to tens of micrometers have been synthesized at large scale in an ammonium metavanadate solution by a templates/catalysts-free route. Such nanobelts grow along the direction of [010]. The individual NH(4)V(3)O(8) nanobelt exhibits nonlinear, symmetric current/voltage (I/V) characteristics, with a conductivity of 0.1-1 S/cm at room temperature and a dielectric constant of approximately 130. The dominant conduction mechanism is based on small polaron hopping due to ohmic mechanism at low electric field below 249 V/cm due to Schottky emission at medium electric field between 249 and 600 V/cm and due to the Poole-Frenkel emission mechanism at high field above 600 V/cm.

Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5 x 7.5 x 7 cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma.