A Simple Model for Cavity Enhanced Slow Lights in Vertical Cavity Surface Emission Lasers

We develop a simple model for the slow lights in Vertical Cavity Surface Emission Lasers (VCSELs), with the combination of cavity and population pulsation effects. The dependences of probe signal power, injection bias current and wavelength detuning for the group delays are demonstrated numerically and experimentally. Up to 65 ps group delays and up to 10 GHz modulation frequency can be achieved in the room temperature at the wavelength of 1.3 $\mu$m. The most significant feature of our VCSEL device is that the length of active region is only several $\mu$m long. Based on the experimental parameters of quantum dot VCSEL structures, we show that the resonance effect of laser cavity plays a significant role to enhance the group delays

BANet: Blur-aware Attention Networks for Dynamic Scene Deblurring

Image motion blur usually results from moving objects or camera shakes. Such blur is generally directional and non-uniform. Previous research efforts attempt to solve non-uniform blur by using self-recurrent multi-scale or multi-patch architectures accompanying with self-attention. However, using self-recurrent frameworks typically leads to a longer inference time, while inter-pixel or inter-channel self-attention may cause excessive memory usage. This paper proposes blur-aware attention networks (BANet) that accomplish accurate and efficient deblurring via a single forward pass. Our BANet utilizes region-based self-attention with multi-kernel strip pooling to disentangle blur patterns of different degrees and with cascaded parallel dilated convolution to aggregate multi-scale content features. Extensive experimental results on the GoPro and HIDE benchmarks demonstrate that the proposed BANet performs favorably against the state-of-the-art in blurred image restoration and can provide deblurred results in real-time

An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma.

Lessons learnedTKM-080301 showed a favorable toxicity profile at the studied dose.TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted

The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.

Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation

Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta

The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR‐1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta . The synthesis features a decarboxylative cross‐coupling reaction of a sulfonic acid‐containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR‐1A derivatives, including fluorescent and photoaffinity‐based probes, allowed quantification of IOR‐1A, localization studies within S. rosetta cells, and evaluation of structure‐activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta . These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta

Induction of Antinuclear Antibodies by De Novo Autoimmune Hepatitis Regulates Alloimmune Responses in Rat Liver Transplantation

Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation

Origin, Transport, and Vertical Distribution of Atmospheric Polluntants over the Northern Sourth China Sea During the 7-SEAS-Dongsha Experiment

During the spring of 2010, comprehensive in situ measurements were made for the first time on a small atoll (Dongsha Island) in the northern South China Sea (SCS), a key region of the 7-SEAS (the Seven South East Asian Studies) program. This paper focuses on characterizing the source origins, transport processes, and vertical distributions of the Asian continental outflows over the region, using measurements including mass concentration, optical properties, hygroscopicity, and vertical distribution of the aerosol particles, as well as the trace gas composition. Cluster analysis of backward trajectories classified 52% of the air masses arriving at ground level of Dongsha Island as having a continental origin, mainly from northern China to the northern SCS, passing the coastal area and being confined in the marine boundary layer (0-0.5 km). Compared to aerosols of oceanic origin, the fine mode continental aerosols have a higher concentration, extinction coefficient, and single-scattering albedo at 550 nm (i.e., 19 vs. 14 microg per cubic meter in PM(sub 2.5); 77 vs. 59 M per meter in beta(sub e); and 0.94 vs. 0.90 in omega, respectively). These aerosols have a higher hygroscopicity (f at 85% RH = 2.1) than those in the upwind inland regions, suggesting that the aerosols transported to the northern SCS were modified by the marine environment. In addition to the near-surface aerosol transport, a significant upper-layer (3-4 km) transport of biomass-burning aerosols was observed. Our results suggest that emissions from both China and Southeast Asia could have a significant impact on the aerosol loading and other aerosol properties over the SCS. Furthermore, the complex vertical distribution of aerosols-coinciding-with-clouds has implications for remote-sensing observations and aerosol-cloud-radiation interactions

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model

KCNN2 polymorphisms and cardiac tachyarrhythmias

Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI] = 1.505-5.545, P = 0.001; and OR 2.55, 95% CI = 1.428-4.566, P = 0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI = 1.025-3.570], P = 0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD

Strukturrevision einer weit verbreiteten marinen Sulfonolipidklasse basierend auf deren Isolierung und Totalsynthese

Bakterien der marinen Roseobacter-Gruppe spielen eine wichtige Rolle in globalen biogeochemischen Prozessen. Prominente Vetreter dieser Gruppe produzieren schwefelhaltige Aminolipide (SAL), die für die Bildung von Biofilmen und die Besiedlung von Meeresoberflächen von entscheidender Bedeutung sind. Obwohl Genome Mining-Ansätze und massenspektrometrische Studien homotaurinhaltige Strukturen für eine Gruppe von SALs postulierten, blieben deren relative und absolute Strukturen bisher unbekannt, was biochemische und funktionelle Untersuchungen behinderte. In dieser Studie konnten wir die absoluten Strukturen durch eine Kombination von analytischen Techniken, Isolierungs- und Abbauexperimenten sowie Totalsynthese bestimmen. Im Gegensatz zu vorherigen Strukturvorschlägen sind die hier untersuchten Aminolipide durch eine ungewöhnliche N,O-acylierte Cysteinolsäure Kopfgruppe gekennzeichnet, weshalb wir die Substanzklasse Cysteinolide genannt haben. Durch gezielte Netzwerk-basierende metabolomische Studien konnten wir zudem die Verteilung und strukturelle Vielfalt von Cysteinoliden in verschiedenee Vertretern der bakteriellen Roseobacter-Gruppe kartieren. Insgesamt konnten in dieser Studie 14 verschiedene Aminolipide, einschließlich der in dieser Studie isolierten Cysteinolide, synthetisiert werden. Der Vergleich der erhaltenen analytischen Daten ermöglichte tiefergehende strukturelle Einblicke in die Charakteristika diese Substanzgruppe, welche für Studien zum bakteriellen Sulfonolipid-Stoffwechsel und zu biogeochemischen Nährstoffkreislauf in den Ozeanen von großer Bedeutung sein werden