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Networks with distinct topological structures varies in the ability to resist different kinds of attacks. Node protection in terms of node importance is an effective way to ensure the reliable communication of networks. Thus, the protection of influential node detected by node importance evaluation is beneficial to strengthen the invulnerability and robustness of networks. In this work, the network agglomeration method based on node contraction is utilized to evaluate the influence of nodes and identify important nodes in five kinds of interconnection networks. We show that the agglomeration method, which takes both the degree and position into account, is valid and feasible for these five interconnection networks.

Traditional fault tolerability is regularly measured by classical vertex or edge connectivity. Menger’s theorem shows that the number of (edge)-disjoint paths is closely related to (edge) connectivity. Clearly, disjoint paths not only provide alternative routings to tolerate faulty vertices but also avoid communication bottlenecks. Furthermore, disjoint paths can speed up the transmission time by distributing data among disjoint paths. In order to assess the fault tolerance of the network objectively, we aim to extend vertex or edge failures to substructure malfunction. In this paper, we show the maximum number of vertex (edge)-disjoint paths in star graph in the case of genetic substructure faults. Let [Formula: see text] ([Formula: see text]) be a [Formula: see text]-dimensional substar of [Formula: see text]. We show that there exist [Formula: see text] vertex (edge)-disjoint paths to connect any two vertices [Formula: see text] and [Formula: see text] in [Formula: see text], where [Formula: see text] is the degree of vertex [Formula: see text] in [Formula: see text]. In addition, we show that (edge) connectivity and [Formula: see text]-extra connectivity of [Formula: see text] are [Formula: see text], [Formula: see text], respectively.

Liver cancer stem cells (LCSCs) cause therapeutic refractoriness and relapse in hepatocellular carcinoma. Heat shock factor 1 (HSF1) plays versatile roles in multiple cancers. However, the role of HSF1 in LCSCs is not well understood. This study investigated the function and signal mechanisms of HSF1 in maintaining LCSC phenotypes.We established two LCSC lines, HepG2-R and HuH-7-R. Constitutive activation of HSF1 was observed in these LCSCs. Specific short hairpin RNAs (shRNAs) and chemical inhibitors were used to identify the relationship between HSF1 expression and LCSCs phenotypes.We revealed a concomitant activation modality involving HSF1 and STAT3 in LCSCs and liver cancer tissues. We also found that liver cancer patients whose HSF1 and STAT3 mRNA expression levels were high presented with unfavorable clinicopathological characteristics. Moreover, the secretion of interleukin-8 (IL-8) was elevated in the LCSC medium and was directly regulated by HSF1 at the transcriptional level. In turn, IL-8 activated HSF1 and STAT3 signaling, and a neutralizing IL-8 antibody inhibited HSF1 and STAT3 activity, reduced cancer stem cell marker expression, and decreased LCSC microsphere formation. Simultaneous intervention with HSF1 and STAT3 led to synergistically suppressed stemness acquisition and growth suppression in the LCSCs in vivo and in vitro.Our study indicates that IL-8 mediates the crosstalk between the HSF1 and Stat3 signaling pathways in LCSCs and that the combined targeting of HSF1 and STAT3 is a promising treatment strategy for patients with advanced liver cancer.

In this work, we determine all the eigenvalues and their corresponding multiplicities of the normalized Laplacian matrix for folded hypercubes. Furthermore, we establish the explicit formula to calculate Kemeny’s constant for random walks on the folded hypercube, which indicates that its growth is roughly consistent with the network order. In addition, we also determine the number of spanning trees and degree-Kirchhoff index of folded hypercubes. Especially, we make some comparisons with that of hypercubes to verify that folded hypercubes have superior properties than hypercubes.

The vertex (edge) connectivity has been regularly used to measure the fault tolerance and reliability of interconnection networks, while it has defects in the assumption that all neighbors of one node will fail concurrently. To overcome this deficiency, some new generalizations of traditional connectivity have been suggested to quantize the size or the number of the connected components of the survival graph. The [Formula: see text]-component (edge) connectivity, one generalization of vertex (edge) connectivity, has been proposed to characterize the vulnerability of multiprocessor systems based on the number of components of the survival graph. In this paper, we determine the [Formula: see text]-component (edge) connectivity of a family of networks, called the round matching composition networks [Formula: see text], which are a class of networks composed of [Formula: see text] ([Formula: see text]) clusters with the same order, linked by [Formula: see text] perfect matchings. By exploring the combinatorial properties and fault-tolerance of [Formula: see text], we establish the [Formula: see text]-component (edge) connectivity [Formula: see text] for [Formula: see text] and [Formula: see text], [Formula: see text] and [Formula: see text] for [Formula: see text].

The peri-implantation period from blastula to gastrula is one of the crucial stages of human embryo and stem cell development. During development, human embryos undergo many crucial events, such as embryonic lineage differentiation and development, structural self-assembly, pluripotency state transition, cell communication between lineages, and crosstalk between the embryo and uterus. Abnormalities in these developmental events will result in implantation failure or pregnancy loss. However, because of ethical and technical limits, the developmental dynamics of human peri-implantation embryos and the underlying mechanisms of abnormal development remain in a “black box.” In this review, we summarize recent progress made toward our understanding of human peri-implantation embryogenesis based on extended in vitro cultured embryos and stem cell–based embryoids. These findings lay an important foundation for understanding early life, promoting research into human stem cells and their application, and preventing and treating infertility. We also propose key scientific issues regarding peri-implantation embryogenesis and provide an outlook on future study directions. Finally, we sum up China’s contribution to the field and future opportunities.

As the only first-line targeted therapy for advanced gastric cancer (GC) with HER2-positive status, the efficacy of trastuzumab is limited by the high rates of primary and secondary resistance. The therapeutic effect of many other HER2-targeted drugs is not satisfactory in GC. Previous studies have demonstrated that overexpression of S-phase kinase-interacting protein 2 (Skp2) predicted poor prognosis of HER2-positive GC and promoted cancer cell proliferation, resistance, and glycolysis. It has been proved that trastuzumab-resistant GC cells exhibit high glycolytic activity. We found thioridazine restores the sensitivity of trastuzumab in vivo and in vitro by inhibiting Skp2 expression and glycolytic activity. Moreover, thioridazine combined with lapatinib also showed strong inhibitory effects on the growth and survival of trastuzumab-resistant GC cells. Collectively, these data introduce a thioridazine-based therapy to overcome trastuzumab resistance in GC.

Background Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into cortical neurons for disease modeling and regenerative medicine. However, these procedures are hard to provide sufficient cells for their applications. Using a combination of small-molecules and growth factors, we previously identified one condition which can rapidly induce hPSCs into neuroepithelial stem cells (NESCs). Here, we developed a scalable suspension culture system, which largely yields high-quality NESC-spheres and subsequent cortical neurons. Methods The NESC medium was first optimized, and the suspension culture system was then enlarged from plates to stirred bioreactors for large-scale production of NESC-spheres by a stirring speed of 60 rpm. During the expansion, the quality of NESC-spheres was evaluated. The differentiation potential of NESC-spheres into cortical neurons was demonstrated by removing bFGF and two pathway inhibitors from the NESC medium. Cellular immunofluorescence staining, global transcriptome, and single-cell RNA sequencing analysis were used to identify the characteristics, identities, purities, or homogeneities of NESC-spheres or their differentiated cells, respectively. Results The optimized culture system is more conducive to large-scale suspension production of NESCs. These largely expanded NESC-spheres maintain unlimited self-renewal ability and NESC state by retaining their uniform sizes, high cell vitalities, and robust expansion abilities. After long-term expansion, NESC-spheres preserve high purity, homogeneity, and normal diploid karyotype. These expanded NESC-spheres on a large scale have strong differentiation potential and effectively produce mature cortical neurons. Conclusions We developed a serum-free, defined, and low-cost culture system for large-scale expansion of NESCs in stirred suspension bioreactors. The stable and controllable 3D system supports long-term expansion of high-quality and homogeneous NESC-spheres. These NESC-spheres can be used to efficiently give rise to cortical neurons for cell therapy, disease modeling, and drug screening in future.

Inflammasome is a complex composed of several proteins and an important part of the natural immune system. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. It plays an important role in many diseases. Hydrogen sulfide (H2S) is an important signaling molecule that regulates many physiological and pathological processes. Recent studies indicated that H2S played anti-inflammatory and pro-inflammatory roles in many diseases through influencing NLRP3 inflammasome, but its mechanism was not fully understood. This article reviewed the progress about the effects of H2S on NLRP3 inflammasome and its mechanisms involved in recent years to provide theoretical basis for in-depth study.

Precise gene regulation is critical during embryo development. Long terminal repeat elements (LTRs) of endogenous retroviruses (ERVs) are dynamically expressed in blastocysts of mammalian embryos. However, the expression pattern of LTRs in monkey blastocyst is still unknown. By single-cell RNA-sequencing (seq) data of cynomolgus monkeys, we found that LTRs of several ERV families, including MacERV6, MacERV3, MacERV2, MacERVK1, and MacERVK2, were highly expressed in pre-implantation embryo cells including epiblast (EPI), trophectoderm (TrB), and primitive endoderm (PrE), but were depleted in post-implantation. We knocked down MacERV6-LTR1a in cynomolgus monkeys with a short hairpin RNA (shRNA) strategy to examine the potential function of MacERV6-LTR1a in the early development of monkey embryos. The silence of MacERV6-LTR1a mainly postpones the differentiation of TrB, EPI, and PrE cells in embryos at day 7 compared to control. Moreover, we confirmed MacERV6-LTR1a could recruit Estrogen Related Receptor Beta (ESRRB), which plays an important role in the maintenance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF and Wnt signaling pathways. In summary, these results suggest that MacERV6-LTR1a is involved in gene regulation of the pre-implantation embryo of the cynomolgus monkeys.

Studies of cultured human embryos have provided insights into human peri-implantation embryogenesis but are limited by ethical and technical constraints. Here we assembled a 3D integrated embryo model (IEM) using naive human embryonic stem cells (hESCs) and hESC-derived proliferating trophoblasts. By comparing phenotypic cell fate and comprehensive single-cell transcriptome of IEMs with 3D-cultured human embryos, we reveal that IEMs with embryonic and extra-embryonic cell types mimic developmental landmarks and 3D morphological features of natural human post­­­ ­­-implantation embryos, including pluripotent state transitions, epithelial-mesenchymal transition, anterior-posterior axis formation, amniotic cavity, yolk sac, bilaminar embryonic disc, extra-embryonic mesenchyme, primitive streak and primordial germ cells. Using IEMs, we unravel composition and gene expression patterns of embryonic lineages, and that trophoblasts secret WNT, BMP and TGFβ/Activin signals to instruct post-implantation embryogenesis . Our findings show that IEMs provide a scalable and tractable model for decoding regulatory mechanisms of human peri-implantation embryogenesis.

For advanced node semiconductor process development, manufacturing, fault isolation and product failure analysis, nanoprobing is an indispensable technology. As the process technology node scales, transistors and materials used are more susceptible to electron beam damage and changes. As scanning electron microscope (SEM) energy decreases to minimize electron beam damage, imaging resolution degrades. Process scaling has not only affected patterning dimensions and pitch scaling, but also materials utilized in advanced nodes. The material used at the contact level has changed from tungsten (W) to cobalt (Co), in combination with ultra-low K dielectrics. These new materials tend to make sample preparation and probing increasingly more challenging. At advanced nodes with sub-20nm contacts, probe landing accuracy and probe-contact stability are important to maintain good electrical contact throughout measurement time. In this paper, we discuss nanoprobing results from a 7nm SRAM obtained from a commercially available leading edge 7nm SOC.

Additional file 1.

The examination of partially deprocessed ICs for well imaging has been investigated. First it has been shown [1] that Ga+ FIB imaging can readily and strongly highlight the N-well / P-well boundary in an IC as shown again here. Second, a model which only considers secondary electron creation and scattering [2] is confirmed to be sufficient for understanding these imaging effects. Heavy Ga doping provides no marked change in PVC (passive voltage contrast). Then comparisons in the same field of view between optimized He+ and Ga+ imaging, has shown that He+ provides much greater PVC contrast when looking through deep oxide, and much better resolution on shallow surfaces. The quantitative model Stopping and Range of Ions in Matter (SRIM) [3] was consulted and confirmed these expectations for resolution and depth superiority of the He+ beam. According to the SRIM, there may even be less damage from the He+ beam. Yet these known effects of Ga+ damage has not prevented its widespread use in semiconductor FA and process monitoring. Thus, the use of GFIS (Gas field ion source) He+ beam for voltage contrast and junction imaging warrants further exploration.

Various culture systems have been used to derive and maintain human pluripotent stem cells (hPSCs), but they are inefficient in sustaining cloning and suspension expansion of hPSCs. Through systematically modulating Wnt and Activin/Nodal signaling, we developed a defined medium (termed AIC), which enables efficient cloning and long-term expansion of hPSCs (AIC-hPSCs) through single-cell passage on feeders, matrix or in suspension (25-fold expansion in 4 days) and maintains genomic stability of hPSCs over extensive expansion. Moreover, the AIC medium supports efficient derivation of hPSCs from blastocysts or somatic cells under feeder-free conditions. Compared to conventional hPSCs, AIC-hPSCs have similar gene expression profiles but down-regulated differentiation genes and display higher metabolic activity. Additionally, the AIC medium shows a good compatibility for different hPSC lines under various culture conditions. Our study provides a robust culture system for derivation, cloning and suspension expansion of high-quality hPSCs that benefits GMP production and processing of therapeutic hPSC products.

Probing is increasingly utilized as a technique for the characterization of the local electrical properties of an integrated circuit, as well as the isolation of defects. Test structures and/or SRAM arrays were examined with the various probing modes available with a probing system. Test structures were examined using Electron Beam Absorbed Current (EBAC), Resistive Contrast Imaging (RCI), Electron Beam Induced Current, (EBIC), and EBIRCH (Electron Beam Induced Resistance CHange). The results demonstrate the utility of using each in an SRAM yield management scenario. EBAC is able to provide information about basic connectivity. RCI allows for the isolation of resistive spots along a conductor. EBIC provides for the imaging of depletion zones between PW and NW, even in a planar view. EBIRCH, being driven by two different mechanisms (thermal coefficient of resistivity and Seebeck effect) is able to provide two different kinds of analyses, depending on the conditions. EBIRCH precisely isolated which of a few fins in a multi-fin device are responsible for a short and showed the thermal relations between the elements of a pulldown device in an SRAM. The techniques together provide multiple forms of process feedback when used as part of an integrated yield management program involving analysis of via chains, SRAM parallel array test structures, and SRAMs.

Summary Monkeys are an optimal model species for developing stem cell therapies. We previously reported generating chimeric cynomolgus monkey fetuses using dome-shaped embryonic stem cells (dESCs). However, conventional primed pluripotent stem cells (pPSCs) lack chimera competency. Here, by altering the media in which injected morulae are cultured, we observed increased survival of cynomolgus monkey primed ESCs, induced PSCs, and somatic cell nuclear transfer-derived ESCs, thereby enabling chimeric contributions with 0.1%–4.5% chimerism into the embryonic and placental tissues, including germ cell progenitors in chimeric monkeys. Mechanically, dESCs and pPSCs belong to different cell types and similarly express epiblast ontogenic genes. The host embryonic microenvironment could reprogram injected PSCs to embryonic-like cells. However, the reprogramming level and chimerism were associated with the cell state of injected PSCs. Our findings provide a method to understand pluripotency and broaden the use of embryonic chimeras for basic developmental biology research and regenerative medicine.

Laser scanning microscope (LSM) based waveform acquisition is widely used in advanced CMOS IC design validation and debug application. Complex waveforms obtained from LSM probing on CMOS ICs are often difficult to fully comprehend without deep understanding of the complex physics involved even in planar CMOS. The introduction of 3-D Tri-Gate transistors since 2010 made this even more challenging. In this paper, we present both model based simulation and probing validations on the most advanced 3D Tri-Gate based CMOS ICs that give us a clear understanding of the nature of these complex waveforms.

We report several cases of two photon absorption (TPA) laser assisted device alteration (LADA) using continuous wave (CW) 1,340 nm laser in Si Complimentary Metal-Oxide Semiconductor (CMOS) Integrated Circuits (IC). Two photon absorption using CW 1,340 nm laser in Si was confirmed by photon beam induced photocurrent measurements. TPA LADA showed greater than two times better resolution in critical timing circuit defect localization and debug application, when compared with traditional single photon absorption (SPA) LADA with CW 1,064 nm laser. A simplified analysis on the resolution improvements presented here showed in good agreement with our experimental observations. Further enhancements of this technology are outlined, which we believe will enable this technology for critical timing circuit debug capabilities well into the future generations of Si CMOS Debug applications.

Logic State Imaging (LSI) using Infra-Red Emission Microscopy (IREM) [1-4] has been an indispensable technology for silicon CMOS process development and product debug applications. Its main limitations are relatively poor spatial resolution due to the broadband near-infrared photons emitted, and poor Signal to Noise Ratio (SNR) with low voltage and low leakage processes and products. Continuous-Wave Laser Scanning Microscope (CW-LSM) based Signal Imaging and Probing (CW-SIP) [5-9] technology is also widely used. It features inherently better spatial resolution than IREM, due to the use of monochromatic 1319nm or 1064nm laser light, and high SNR due to its weaker dependence on voltage and leakage, and, for signal imaging applications, the use of narrow band detection to reduce noise. However, CW-SIP can only detect modulating signals, so it couldn’t previously be applied to LSI. In this paper, we introduce an innovative approach that overcomes this limitation to enable Laser Logic State Imaging (LLSI). Actual fault isolation and design debug cases using this technology are presented to show its advantages in terms of resolution (>50% better), SNR (>2X better) and throughput time improvement, especially at low voltages (down to 500mV).

The metastasis is one of the greatest challenges for successful cancer therapy. Herein, we report a lipid-coated nanodiamond (ND) system loading water-insoluble sorafenib (SND) to improve the bioavailability and efficacy on suppression of cancer metastasis. SND was homogenous nanoassemblies with the mean diameter of 127.6 ± 12.9 nm. Compared with the drug suspension, the sorafenib concentration in gastrointestinal (GI) tract and major organs was significantly increased by SND. Moreover, the oral bioavailability of sorafenib was greatly improved 7.64-fold by SND. However, the ND in SND could not be absorbed into the mucus of GI tract or distributed into major organs after oral administration. Furthermore, the sorafenib concentration in tumor tissue was markedly improved 14.95 folds by SND, and SND demonstrated an efficient and impressive tumor growth inhibition effect in tumor xenograft models. In particular, the metastasis of gastric cancer to distant organs of liver and kidney was remarkably suppressed by SND, which was verified by the detection of macroscopic metastatic nodules, histological examination and immunofluorescence measurements. Thereby, the lipid-coated ND could be a promising drug delivery platform for improving the oral bioavailability of lipophilic drugs and treatment of cancer metastasis.

We are reporting on the development of a unique drug delivery platform by directed self-assembly technique to improve the oral delivery of hydrophobic drugs.Herein, a series of probucol directed self-assembled nanoparticles (PDN) were developed with two components of probucol and surfactant such as Tween 20, Tween 80, D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and HS-15, which was respectively named as T20-PDN, T80-PDN, TP-PDN and HS-PDN. The formation of various PDNs was determined by in vitro characterization and the physicochemical properties of these PDNs were determined. Moreover, the performance of PDN in enhancing the oral delivery and possible correlation between the in vitro properties and in vivo performances were investigated.PDN was homogenous nanometer-sized particles with negative surface charge. The cellular uptake of probucol in Caco-2 cell monolayer was respectively increased 1.15, 1.82, 1.59 and 5.31-fold by these PDN. In particular, the oral bioavailability of these PDN was significantly improved 3.0, 4.1, 5.4 and 10.4 folds compared with the free drug suspension. The enhanced cellular uptake and oral bioavailability were correlated with the characters of involved surfactants and the particle size of PDN.Thereby, the directed self-assembled nanoparticles could provide a new strategy for enhancing the oral delivery of hydrophobic drugs.

Single‐photon threshold photoionization has been used to explore the ionization dynamics of the NH+3 (X 2A2″)←NH3 (X 1A1) transition which involves a pyramidal‐to‐planar geometry change. Rotationally resolved threshold photoelectron spectra are presented for four vibrational levels of the X 2A2″ cation state of NH+3 corresponding to excitation of even and odd quanta of the inversion mode, ν+2. The rotational state distributions exhibit strong symmetry effects imposed by the nuclear spin statistics and vibronic parity of the neutral and cation out‐of‐plane bend levels. The observed rotational structure is consistent with dominant ΔK=0 transitions and parity assignments for specific transitions show that both l=even and l=odd photoelectron final states are excited. These observations indicate that the photoelectron experiences a non‐planar (pyramidal) cation potential. These results are discussed in light of previous rotationally resolved measurements on NH3 using multiphoton ionization and other systems ...

A novel method for obtaining diffraction limited high resolution images, and increased signal to noise ratio (SnR), for imaging and probing silicon based complementary metal oxide semiconductor field effect transistor (CMOS, and MOSFET) integrated circuits (IC), is presented. The improved imaging is based on the sub wavelength features’ asymmetric layout, which is dictated by the lithography design rules constrain in CMOS IC and their interactions with polarized light. This asymmetry in layout and the inherent stress engineering on the CMOS IC, produce both dichroism and birefringence in silicon (Si). An elegant design enabled us to obtain two images with orthogonal polarization detection to take advantages of the dichroism and birefringence in Si based CMOS IC. Differential Polarization Image (DPI) is obtained by subtracting the two orthogonal polarization resolved images. On infrared emission microscopes (IREM), DPI in optical imaging mode and DPI plus probing [DPIP] in emission mode, showed 2X or more in terms of optical resolution (imaging mode) and 2X or more SnR (emission-probing mode) improvements. Striking images in probing mode, revealing previously “invisible” emission, were demonstrated.

As device dimensions continue to shrink, process defects tend to become more subtle. For most failure analysis (FA) studies, it is important to identify the defect location for the subsequent material analysis. To achieve this, nano-probing has been widely used in the FA community. Copper (Cu) contacts posed a significant challenge to nano-probing since Cu is soft and tends to deform during measurements. In addition, Cu oxidizes quickly in air, increasing contact resistance significantly between the probes and devices. This paper introduces electroless cobalt (Co) plating on Cu contacts for nano-probing to overcome these technical problems. As Cu is soft and oxidized quickly in air, the technique presented in this paper provides a technical solution for nano-probing on Cu contacts. With carefully characterized Co plating time, this technique can be used not only on Cu contacts but also on Cu interconnection.

High resolution helium Iα (584 A) photoelectron spectra of H2CO and D2CO are reported. The present study reveals much new vibrational structure detail in the ionic first excited state of formaldehyde. Weak excitations of the ν3 (in H2CO) and ν1 (in D2CO) modes along with the strong excitations of the ν2 mode in the ionic first excited states are fully resolved for the first time. The weak excitations of the ν4 out‐of‐plane bending mode in the ionic ground and first excited states of formaldehyde cations indicate that they may have nonplanar equilibrium geometries. Strong isotope effects on vibronic (vibrational) couplings are observed in the cation first and second excited states. Vibrational autocorrelation functions are calculated from the high‐resolution photoelectron spectra. The correlation functions calculated for the first electronic excited states show rather slow decay rate on the femtosecond time scale. The ultrafast decay of the formaldehyde cations implied by the correlation functions calculated for the third electronic excited states suggest that dissociation and intramolecular dynamic processes are the main decay pathways.

High-resolution helium Iα (584 A) photoelectron spectra of H2CO and D2CO using supersonic molecular beams are reported. The excitation of the ν4 out-of-plane bending mode in the ionic ground state and the first excited state imply that formaldehyde cations in these states might have non-planar equilibrium geometries. The different vibrational progressions observed in the first and second excited states indicate strong isotope effects on vibrational (vibronic) couplings. The adiabatic ionization energies and spectroscopic constants for all four ionic states are reported to a much higher accuracy than previously available.

In this paper, we report on the first observation and study of two-photon absorption (TPA) based laser assisted device alteration (LADA) using a continuous-wave (CW) 1340nm laser. The study was conducted using LADA systems equipped with high numerical aperture (NA) liquid and solid immersion lens objectives on Intel’s 45 nm and 32 nm multiprocessor units (MPU) and test chips. The power densities achievable using these lenses are similar to those reported in the literature for TPA in silicon of CW 1455nm light [1]. We show that the induced photocurrent has a quadratic dependence on the input laser power, a key indicator of two-photon phenomenon. Our results imply that even when using 1340nm wavelength CW lasers, there is a potential for laser invasiveness with the high power densities achievable using high NA objectives. Laser induced damage of the DUT is also a possibility at these high power densities, particularly with the solid immersion lens (SIL). However, we show that the DUT damage threshold can be increased by reducing the DUT’s temperature. Finally, we present results demonstrating a >40% improvement in localization of critical timing faults using TPA based LADA, when compared to traditional 1064nm wavelength (single-photon absorption) LADA.

Radial glial cells are stem cells that play an important role in neuronal migration and proliferation in the developing brain. However, how radial glial cells contribute to the lamination of the cerebellar cortex is not well understood. We therefore used immunohistochemistry and BrdU labeling to follow radial glial cell differentiation, cell migration and cerebellar cortex development in mice from embryonic day 8 to postnatal day 180. We report that radial glial cells represent the stem cell population of the neuroepithelium of the neural tube, and act as progenitors for both neurons and neuroglia. In addition, radial glial cells not only give rise to the principal cells of the cerebellar cortex, the Purkinje and granule cells, but they also provide a scaffold for the migration of these cells. We conclude that radial glial cells play a pivotal role in establishing the laminar structure of the cerebellar cortex.

High resolution He I{alpha} photoelectron spectroscopy of formaldehyde and ketene and their deuterated compounds, are reported. The combination of a (H2CO) double-pass high-resolution electron-energy analyzer and effective rotational cooling of the sample by supersonic expansion enable the spectroscopy of these molecular cations. The vibrational autocorrelation functions are calculated from the high-resolution photoelectron spectra, shedding light on the ultrafast intramolecular dynamics of the molecular cations. This study reveals much more vibrational structural detail in the first electronic excited state of H2CO cations. The first electronic excited state of H2CO cations may have nonplanar equilibrium geometry. Strong isotope effects on vibronic (vibrational) coupling are observed in the second electronic excited state of H2CO. Vibrational autocorrelation functions are calculated for all four observed electronic states of H2CO. The correlation function of the first electronic excited state of H2CO shows a slow decay rate on the femtosecond time scale. The ultrafast decay of the H2CO cations in the third electronic excited state implies that dissociation and intramolecular processes are the main decay pathways. The present spectra of the ground states of ketene cations have more fine structure than before. The AIEs of the first and fifth excited states are determined unambiguously more accurately. Themore » doublet-like fine structures present in the lint excited state of ketene implies the excitation of a ``soft`` mode not observed before. The vibrational autocorrelation functions are calculated for 4 of the 6 observed electronic states. The dynamics of the ground states of the cations are characterized by a wave packet oscillating with small amplitude around the minimum on the upper PES. The decay dynamics of the first and the fifth excited states of ketene are characterized by ultra-fast intramolecular processes like predissociation.« less

Photoelectron spectra of the negatively charged clusters of CO2 are recorded with 3.49 eV photon energy and appear as bell‐shaped, unresolved vibrational envelopes similar to that observed for the monomer ion. The maxima of the photoelectron spectra, found by fitting the envelopes to Gaussian profiles, correspond to the vertical electron detachment energies (VDE) of the clusters. These VDE values, when combined with the previously measured value for CO−2, display sharp discontinuities at cluster sizes n=2 and n=6. The magnitudes of these shifts are on the order of 1 eV and are in near quantitative agreement with the calculated difference in VDE between the monomer anion and the D2d form of the dimer anion. We infer from this agreement that the dimer ion is the core of clusters 2≤n≤5 while the monomer ion forms the core for n≥7. The hexamer is special in that both forms are evident in the photoelectron spectra. These structural changes are not manifested as ‘‘magic numbers’’ in the parent spectra, which have been previously observed at n=4, 7, 10, and 14.