Hematopoiesis and T-cell specification as a model developmental system

The pathway to generate T cells from hematopoietic stem cells guides progenitors through a succession of fate choices while balancing differentiation progression against proliferation, stage to stage. Many elements of the regulatory system that controls this process are known, but the requirement for multiple, functionally distinct transcription factors needs clarification in terms of gene network architecture. Here, we compare the features of the T-cell specification system with the rule sets underlying two other influential types of gene network models: first, the combinatorial, hierarchical regulatory systems that generate the orderly, synchronized increases in complexity in most invertebrate embryos; second, the dueling ‘master regulator’ systems that are commonly used to explain bistability in microbial systems and in many fate choices in terminal differentiation. The T-cell specification process shares certain features with each of these prevalent models but differs from both of them in central respects. The T-cell system is highly combinatorial but also highly dose-sensitive in its use of crucial regulatory factors. The roles of these factors are not always T-lineage-specific, but they balance and modulate each other's activities long before any mutually exclusive silencing occurs. T-cell specification may provide a new hybrid model for gene networks in vertebrate developmental systems

Facile synthesis of a nickel sulfide (NiS) hierarchical flower for the electrochemical oxidation of H2O2 and the methanol oxidation reaction (MOR).

The synthesis of a novel hierarchical flower-like NiS via a solvothermal method for the electrochemcial oxidation of H2O2 on a carbon paste electrode with high catalytic activity for the (MOR) in an alkaline medium has been reported. Novel nickel sulfide (NiS) hierarchical flower-like structures were characterized by X-ray diffraction, scanning electron microscope, and transmission electron microscopy. A carbon paste electrode was modified with the as-prepared hierarchical flower-like NiS, resulting in a high electrocatalytic activity toward the oxidation of H2O2. The NiS-modified electrode was used for H2O2 sensing, which was achieved over a wide linear range from 0.5 μMto1.37mM(I/μA =-0.19025 + 0.06094 C/mM) with a low limit of detection (LOD) of 0.3 μM and a limit of quantitation (LOQ) of 0.8 μM. The hierarchical flower-like NiS also exhibited a high electrocatalytic activity for the methanol oxidation reaction (MOR) in an alkaline medium with a high tolerance toward the catalyst-poisoning species generated during the MOR. The MOR proceeded via the direct electrooxidation of methanol on the oxidized NiS surface layer because the oxidation peak potential of the MOR was more positive than that of the oxidation of NiS

Wafer Level Package for Image Sensor Module

A new ISM (image sensor module) WLP (wafer level package) for reflow process is designed, fabricated and tested. The ISM WLP is composed of polymer bonding layer, glass cap wafer for particle free process and CIS (CMOS Image Sensor) chip wafer which has micro via hole interconnection. During the last decades, WLP is highlighted as the next generation ISM Package method for many advantages like high yield (particle free process), small form factor (3D interconnection), low assembly cost and so on. Nevertheless these benefits, there are some problems like micro via hole fabrication, low temperature insulation process (inside hole), bottom side oxide etching, warpage control according to wafer level bonding using different material, and whole process temperature limitation for micro lens damage. Among various fabrication methods for ISM package, COB (Chip on board), COF (Chip on film), and L, T contact WLP from ShellCase are generally used. In case of COB and COF package, it has difficulty in particle control during assembly process. In case of ShellCase type WLP has very complicated fabrication process. Additionally, most of above package has disadvantage in size point of view. Through suggested ISM WLP using through interconnection via, wafer level fabrication & packaging technology is realized. It can not only solve problems of conventional packaging structures but also tremendously reduce the manufacturing & assembly cost (include time) of ISM package and realize real chip scale package. Based on sensor size, 3.67 X 3.42 X 0.39 (H) mm3 WLP is designed. During the parametric study using commercial 3-D simulation programs, silicon thickness, polymer bonding layer thickness, and glass thickness were chose the effective factor. And considering the optical and electrical analysis, we decide the parameter : silicon thickness is 0.1mm, polymer bonding layer thickness is 0.04mm, and glass thickness is 0.25mm. The fabrication process is composed bonding layer patterning, wafer bonding, thinning, via etching, passivation layer deposition, bottom oxide opening, metal plating, bottom electrode patterning, solder ball formation, and dicing. A new concept of ISM WLP has been founded to be suitable structure for low cost, small form factor application. We took good quality photo image using realized ISM WLP and obtained high electrical characteristics. Resist from GND to GND pad is measured 2.5 ohms. This package is realized with simple wafer level package technology. The proposed wafer level package can find applications, such as a next image sensor module

A unique iridium(III) complex-based chemosensor for multi-signal detection and multi-channel imaging of hypochlorous acid in liver injury

Although hypochlorous acid (HOCl) has long been associated with a number of inflammatory diseases in mammalian bodies, the functions of HOCl in specific organs at abnormal conditions, such as liver injury, remain unclear due to its high reactivity and the lack of effective methods for its detection. Herein, a unique Ir(III) complex-based chemosensor, Ir-Fc, was developed for highly sensitive and selective detection of HOCl. Ir-Fc was designed by incorporating a ferrocene (Fc) quencher to a Ir(III) complex through a HOCl-responsive linker. In the presence of HOCl, the fast cleavage of Fc moiety in less than 1s led to the enhancement of photoluminescence (PL) and electrochemical luminescence (ECL), by which the concentration of HOCl was determined by both PL and ECL analysis. Taking advantages of excellent properties of Ir(III) complexes, optical and electrochemical analyses of the response of Ir-Fc towards HOCl were fully investigated. Followed by the measurements of low cytotoxicity of Ir-Fc by MTT analysis, one-photon (OP), two-photon (TP) and lifetime imaging experiments were conducted to visualise the generation of HOCl in live microphage and HepG2 cells, and in zebrafish and mouse, respectively. Furthermore, the generation and distribution of HOCl in liver cells and liver injury of zebrafish and mouse were investigated. The results demonstrated the applicability of Ir-Fc as an effective chemosensor for imaging of HOCl generation in mitochondria of cells and liver injury in vivo, implying the potential of Ir-Fc for biomedical diagnosis and monitoring applications

Impaired large-scale cortico–hippocampal network connectivity, including the anterior temporal and posterior medial systems, and its associations with cognition in patients with first-episode schizophrenia

Background and objectiveThe cortico–hippocampal network is an emerging neural framework with striking evidence that it supports cognition in humans, especially memory; this network includes the anterior temporal (AT) system, the posterior medial (PM) system, the anterior hippocampus (aHIPPO), and the posterior hippocampus (pHIPPO). This study aimed to detect aberrant patterns of functional connectivity within and between large-scale cortico–hippocampal networks in first-episode schizophrenia patients compared with a healthy control group via resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the correlations of these aberrant patterns with cognition.MethodsA total of 86 first-episode, drug-naïve schizophrenia patients and 102 healthy controls (HC) were recruited to undergo rs-fMRI examinations and clinical evaluations. We conducted large-scale edge-based network analysis to characterize the functional architecture of the cortico–hippocampus network and investigate between-group differences in within/between-network functional connectivity. Additionally, we explored the associations of functional connectivity (FC) abnormalities with clinical characteristics, including scores on the Positive and Negative Syndrome Scale (PANSS) and cognitive scores.ResultsCompared with the HC group, schizophrenia patients exhibited widespread alterations to within-network FC of the cortico–hippocampal network, with decreases in FC involving the precuneus (PREC), amygdala (AMYG), parahippocampal cortex (PHC), orbitofrontal cortex (OFC), perirhinal cortex (PRC), retrosplenial cortex (RSC), posterior cingulate cortex (PCC), angular gyrus (ANG), aHIPPO, and pHIPPO. Schizophrenia patients also showed abnormalities in large-scale between-network FC of the cortico–hippocampal network, in the form of significantly decreased FC between the AT and the PM, the AT and the aHIPPO, the PM and the aHIPPO, and the aHIPPO and the pHIPPO. A number of these signatures of aberrant FC were correlated with PANSS score (positive, negative, and total score) and with scores on cognitive test battery items, including attention/vigilance (AV), working memory (WM), verbal learning and memory (Verb_Lrng), visual learning and memory (Vis_Lrng), reasoning and problem-solving (RPS), and social cognition (SC).ConclusionSchizophrenia patients show distinct patterns of functional integration and separation both within and between large-scale cortico–hippocampal networks, reflecting a network imbalance of the hippocampal long axis with the AT and PM systems, which regulate cognitive domains (mainly Vis_Lrng, Verb_Lrng, WM, and RPS), and particularly involving alterations to FC of the AT system and the aHIPPO. These findings provide new insights into the neurofunctional markers of schizophrenia

Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network

T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein. However, the role of lineage commitment factor Bcl11b has been unclear. We use self-organizing maps on 63 RNA-seq datasets from normal and perturbed T-cell development to identify functional targets of Bcl11b during commitment and relate them to other regulomes. We show that both activation and repression target genes can be bound by Bcl11b in vivo, and that Bcl11b effects overlap with E2A-dependent effects. The newly clarified role of Bcl11b distinguishes discrete components of commitment, resolving how innate lymphoid, myeloid, and dendritic, and B-cell fate alternatives are excluded by different mechanisms

A Low-cost Through Via Interconnection for ISM WLP

WLP (Wafer level packaging) for image sensor devices has the advantage of small size, high performance and low cost, and becomes more and more important for ISM (image sensor module) products. In the WLP technology, in order to form electrical interconnection from image sensor contact pad to the backside of the wafer, several structures have been developed such as T-contact and TSV (Through Silicon Via). In this paper, a wafer level package of image sensor with new type TSV electrical interconnection for image sensor pad is presented. The target of this development is to reduce process cost and difficulty, and increase yield of image sensor packaging. Basic vertical via shape and low cost interconnection processes are adopted, compared to tapered via interconnection processes. Via etch problem caused by CIS wafer thickness non-uniformity was solved by remaining a fillet structure at the bottom of vias. This structure can prevent via notch and give better result of seed layer deposition and via filling

A far downstream enhancer for murine Bcl11b controls its T-cell specific expression

Bcl11b is a T-cell specific gene in hematopoiesis that begins expression during T-lineage commitment and is required for this process. Aberrant expression of BCL11B or proto-oncogene translocation to the vicinity of BCL11B can be a contributing factor in human T-ALL. To identify the mechanism that controls its distinctive T-lineage expression, we corrected the identified Bcl11b transcription start site and mapped a cell-type–specific differentially methylated region bracketing the Bcl11b promoter. We identified a 1.9-kb region 850 kb downstream of Bcl11b, “Major Peak,” distinguished by its dynamic histone marking pattern in development that mirrors the pattern at the Bcl11b promoter. Looping interactions between promoter-proximal elements including the differentially methylated region and downstream elements in the Major Peak are required to recapitulate the T-cell specific expression of Bcl11b in stable reporter assays. Functional dissection of the Major Peak sequence showed distinct subregions, in which TCF-1 sites and a conserved element were required for T-lineage–specific activation and silencing in non-T cells. A bacterial artificial chromosome encompassing the full Bcl11b gene still required the addition of the Major Peak to exhibit T-cell specific expression. Thus, promoter-proximal and Major Peak sequences are cis-regulatory elements that interact over 850 kb to control expression of Bcl11b in hematopoietic cells

Supersymmetric dS/CFT

We put forward new explicit realisations of dS/CFT that relate ${\cal N}=2$ supersymmetric Euclidean vector models with reversed spin-statistics in three dimensions to specific supersymmetric Vasiliev theories in four-dimensional de Sitter space. The partition function of the free supersymmetric vector model deformed by a range of low spin deformations that preserve supersymmetry appears to specify a well-defined wave function with asymptotic de Sitter boundary conditions in the bulk. In particular we find the wave function is globally peaked at undeformed de Sitter space, with a low amplitude for strong deformations. This suggests that supersymmetric de Sitter space is stable in higher-spin gravity and in particular free from ghosts. We speculate this is a limiting case of the de Sitter realizations in exotic string theories.Comment: V2: references and comments added, typos corrected, version published in JHEP; 27 pages, 3 figures, 1 tabl