We consider the problem of reconstructing a gene regulatory network structure from limited time series gene expression data, without any a priori knowledge of connectivity. We assume that the network ...is sparse, meaning the connectivity among genes is much less than full connectivity. We develop a method for network reconstruction based on compressive sensing, which takes advantage of the network's sparseness.
For the case in which all genes are accessible for measurement, and there is no measurement noise, we show that our method can be used to exactly reconstruct the network. For the more general problem, in which hidden genes exist and all measurements are contaminated by noise, we show that our method leads to reliable reconstruction. In both cases, coherence of the model is used to assess the ability to reconstruct the network and to design new experiments. We demonstrate that it is possible to use the coherence distribution to guide biological experiment design effectively. By collecting a more informative dataset, the proposed method helps reduce the cost of experiments. For each problem, a set of numerical examples is presented.
The method provides a guarantee on how well the inferred graph structure represents the underlying system, reveals deficiencies in the data and model, and suggests experimental directions to remedy the deficiencies.
The incidence and mortality of hepatocellular carcinoma (HCC) have decreased over time in South Korea, where hepatitis B virus (HBV) in endemic. This study investigated the changes in the ...characteristics and clinical outcomes of HCC patients in Korea.
Patients initially diagnosed with HCC and treated at the National Cancer Center, Korea between 2000 and 2015 (n = 4,291) were followed up until February 2017. Differences in patient characteristics and outcomes were compared between chronological cohorts: cohort A (2000-2004, n = 1,157) vs. B (2005-2009, n = 1,678) vs. C (2010-2015, n = 1,456).
The median age of the patient cohort was 57 years (range, 13-98 years), and male predominance was noted (81.6%). HBV infection was the most common etiology (74.8%). The proportion of patients diagnosed with good liver function and small tumors (<2 cm) increased significantly over time: 74.6%, 79.9%, and 87.4% for Child-Pugh class A (p<0.001) and 8.0%, 8.5%, and 12.0% for modified UICC stage I (p<0.001) in cohorts A, B, and C, respectively. Median overall survival improved significantly over time: 14.4 months (95% confidence interval CI, 12.0-16.8 months), 22.9 months (95% CI, 20.3-25.5 months), and 53.6 months (95% CI, 45.7-61.5 months) in cohorts A, B, and C, respectively. HBV-related patients showed significantly improved survival (12.7 vs. 20.4 vs. 64.5 months, p<0.001) associated with the use of antiviral treatments (adjusted hazard ratio, 0.72; 95% CI, 0.64-0.80).
The survival of patients with HCC, especially HBV-related HCC, has improved significantly over time in Korea.
In this study, we sequenced and assembled the genome of a European estuarine calanoid copepod using Oxford Nanopore PromethION and Illumina HiSeq 2500 platforms. The length of the assembled genome ...was 776.1 Mb with N50 = 474.9 kb (BUSCO 85.9%), and the genome consisted of 2473 contigs. A total of 18,014 genes were annotated and orthologous gene clusters were analyzed in comparison to other copepods. In addition, genome-wide identification of cytochrome P450s, glutathione S-transferases, and ATP-binding cassette transporters in E. affinis was performed to determine gene repertoire of these detoxification-related gene families. Results revealed the presence of species-specific gene inventories, indicating that these gene families have evolved through species-specific gene loss/expansion processes, possibly due to adaptation to different environmental stressors. Our study provides a new inventory of the European estuarine calanoid copepod E. affinis genome with emphasis on phase I, II, and III detoxification systems.
•The length of the assembled genome was 776.1 Mb with N50 = 474.9 kb (BUSCO 85.9%).•A total of 18,014 genes were annotated in European calanoid copepod Eurytemora affinis.•Cytochrome P450s, glutathione S-transferases, and ATP-binding cassette proteins genes were fully identified.
Cu deposition on the surface of spherical SiO2 nanoparticles was studied to achieve the hybrid structure of Cu-SiO2 nanocomposite. SiO2 nanoparticles served as seeds for continuous Cu metal ...deposition. The chemical structure and morphology were studied with X-ray photoelectron spectroscopy (XPS), scanning electron microscope energy dispersive X-ray (SEM-EDX), and a transmission electron microscope (TEM). The antibacterial properties of the Cu−SiO2 nanocomposite were examined with disk diffusion assays. The homogeneously formed Cu nanoparticles on the surface of SiO2 nanoparticles without aggregation of Cu nanoparticles showed excellent antibacterial ability.
Abstract Purpose To evaluate clinical effectiveness and safety of simultaneous integrated boost-proton beam therapy (SIB-PBT) in hepatocellular carcinoma (HCC) patients with tumour vascular ...thrombosis (TVT). Material and methods Forty-one HCC patients with TVT underwent SIB-PBT using three dose-fractionation schemes: if gross tumour volume <1 cm ( n = 27), 1–1.9 cm ( n = 7), and ⩾2 cm ( n = 7) from gastrointestinal structures, 50 GyE (EQD2, 62.5 GyE10 ), 60 Gy (EQD2, 80 GyE10 ), 66 Gy (EQD2, 91.3 GyE10 ), respectively, in 10 fractions was prescribed to planning target volume 1 (PTV1), and 30 GyE (EQD2, 32.5 GyE10 ) in 10 fractions was prescribed to PTV2. Results Overall, treatment was well tolerated, with no grade toxicity ⩾3. Median overall survival (OS) was 34.4 months and 2-year local progression-free survival (LPFS), relapse free survival (RFS), and OS rates were 88.1%, 25%, and 51.1%, respectively. Patients treated with EQD2 of ⩾80 GyE10 tended to show better TVT response (92.8% vs. 55.5%, p = 0.002) 2-year LPFS (92.9% vs. 82.5%, p = 0.463), RFS (28.8% vs. 19%, p = 0.545), and OS (58.4% vs. 46.8%, p = 0.428) rates than those with EQD2 of <80 GyE10 . Multivariate analysis showed that TVT response and Child Pugh classification were independent prognostic factors for OS. Conclusions SIB-PBT is feasible and promising for HCC patients with TVT.
Many discoveries in cell biology rely on making specific proteins visible within their native cellular environment. There are various genetically encoded tags, such as fluorescent proteins, developed ...for fluorescence microscopy (FM). However, there are almost no genetically encoded tags that enable cellular proteins to be observed by both FM and electron microscopy (EM). Herein, we describe a technology for labeling proteins with diverse chemical reporters, including bright organic fluorophores for FM and electrondense nanoparticles for EM. Our technology uses versatile interacting peptide (VIP) tags, a class of genetically encoded tag. We present VIPER, which consists of a coiled-coil heterodimer formed between the genetic tag, CoilE, and a probe-labeled peptide, CoilR. Using confocal FM, we demonstrate that VIPER can be used to highlight subcellular structures or to image receptor-mediated iron uptake. Additionally, we used VIPER to image the iron uptake machinery by correlative light and EM (CLEM). VIPER compared favorably with immunolabeling for imaging proteins by CLEM, and is an enabling technology for protein targets that cannot be immunolabeled. VIPER is a versatile peptide tag that can be used to label and track proteins with diverse chemical reporters observable by both FM and EM instrumentation.
This paper presents the results of short-term durability test for GFRP rods exposed to various environmental conditions. The main objective of this study is to investigate the degradation of GFRP ...composite using an accelerated aging method and its influence on the tensile properties. Two types of E-glass/vinylester rods were exposed to moisture, chloride, alkali, and freeze-thaw cycling conditions for up to 132 days. In order to examine the degradation of the GFRP composite in micro level, strand-type E-glass/vinylester rod specimens were also fabricated and tested. The test results indicated that the tensile properties of the GFRP rods were significantly reduced after conditioning, due to the degradation of GFRP.
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•(0.99‒x)Bi1/2Na1/2TiO3‒0.01KTaO3‒xSrTiO3 (BNT‒KT‒100xST) ceramics as BNT‒based a new ternary system were successfully synthesized in this study.•Ferroelectrics‒to‒relaxor phase ...transition was induced by ST modification that was originated from the interrupted long-range ferroelectric order.•A high normalized strain of 793 kV/mm at a low electric field (3 kV/mm) was obtained in BNT‒KT‒22.5ST lead‒free piezoelectric ceramics.•We believe that BNT‒KT‒22.5ST lead‒free piezoelectric ceramics can be a promising candidate for actuator applications.
This study investigated the structures, dielectric, ferroelectric and piezoelectric properties of (0.99‒x)Bi1/2Na1/2TiO3‒0.01KTaO3‒xSrTiO3 (BNT‒KT‒100xST, x = 0.20 ˜ 0.235) lead‒free piezoelectric ceramics. These piezoceramics were synthesized by conventional solid‒state reaction method. As a consequence, a large electrical strain and normalized strain (d33* ≈ 793 pm/V) can be obtained even under 3 kV/mm as low electric field for BNT‒KT−22.5ST ceramics. The phase transition between nonergodic relaxor (NER) and ergodic relaxor (ER) under electric field might be responsible for its large strain. It means that BNT‒KT‒100xST lead‒free ceramics can be a promising candidate for actuator applications.
The drivers of ductal carcinoma
(DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to ...evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions. Immune "hot" and "cold" tumors can arise as early as DCIS and are subtype-specific. Topologic analysis showed a similar degree of pan-leukocyte-tumor mixing in both DCIS and IDC but differ when assessing specific immune subpopulations such as CD4 T cells and CD68 macrophages. Tumor-specific copy-number aberrations in MHC-I presentation machinery and losses in 3p, 4q, and 5p are associated with differences in immune signaling in estrogen receptor (ER)-negative IDC. Common oncogenic hotspot mutations in genes including
and
are predicted to be neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition, and are associated with differences in immune signaling. We highlight both tumor and immune-specific changes in the transition of pure DCIS to IDC, including genetic changes in tumor cells that may have a role in modulating immune function and assist in immune escape, driving the transition to IDC. IMPLICATIONS: We demonstrate that the
to IDC evolutionary bottleneck is shaped by both tumor and immune cells.
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