We show that it is possible to use gravitational wave detectors to observe the occurrence of a first order phase transition in Pati-Salam extensions of the Standard Model. We show that the peak ...frequency of the expected gravitational wave signals ranges within 0.1–10 Hz. We find amusing that the next generation of gravity waves detectors are able to explore time-honored extensions of the Standard Model occurring at energy scales inaccessible by present and future particle physics accelerators.
Although the contribution of the bone marrow mesenchymal stem cells (BM-MSCs) in cancer progression is emerging, their potential roles in prostate cancer (PCa) remain unclear. Here, we showed that ...PCa cells could recruit BM-MSCs and consequently the metastatic ability of PCa cells was increased. We also found that the increased metastatic ability of PCa cells could be due to the increased PCa stem cell population. Mechanism dissection studies found that the upregulation of Chemokine ligand 5 (CCL5) expression in BM-MSCs and PCa cells, after MSCs infiltrated into the PCa cells, subsequently downregulated androgen receptor (AR) signaling, which was due to inhibition of AR nuclear translocation. Interruption of such signaling led to suppression of the BM-MSCs-induced PCa stem cell population increase and thereby inhibited the metastatic ability of PCa cells. The PCa stem cell increase then led to the upregulation of matrix metalloproteinase 9, ZEB-1, CD133 and CXCR4 molecules, and enhanced the metastatic ability of PCa cells. Therefore, we conclude that the BM-MSCs-mediated increased metastatic ability of PCa cells can be due to the PCa stem cell increase via alteration of the CCL5-AR signaling pathway. Together, these results uncover the important roles of BM-MSCs as key components in the prostate tumor microenvironment to promote PCa metastasis and may provide a new potential target to suppress PCa metastasis by blocking BM-MSCs infiltration into PCa.
Summary
Background
Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects ...survival after HCC diagnosis.
Methods
This was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.
Results
Approximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).
Conclusions
Anti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.
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Due to the poor self-regeneration of brain tissue, stem cell transplantation therapy is purported to enable the replacement of lost neurons after traumatic brain injury (TBI). The ...main challenge of brain regeneration is whether the transplanted cells can survive and carry out neuronal functions in the lesion area. The brain is a complex neuronal network consisting of various types of cells that significantly influence on each other, and the survival of the implanted stem cells in brain is critically influenced by the surrounding cells. Although stem cell-based therapy is developing rapidly, most previous studies just focus on apply single type of stem cells as cell source. Here, we found that co-culturing human umbilical cord mesenchymal stem cells (hUC-MSCs) directly with the activated astrocytes benefited to the proliferation and neuron differentiation of hUC-MSCs in vitro. In this study, hUC-MSCs and the activated astrocytes were seeded in RADA16-BDNF peptide scaffold (R-B-SPH scaffold), a specifical self-assembling peptide hydrogel, in which the environment promoted the differentiation of typical neuron-like cells with neurites extending in three-dimensional directions. Moreover, the results showed co-culture of hUC-MSCs and activated astrocytes promoted more BDNF secretion which may benefit to both neural differentiation of ectogenic hUC-MSCs and endogenic neurogenesis. In order to promote migration of the transplanted hUC-MSCs to the host brain, the hUC-MSCs were forced with CXC chemokine receptor 4 (CXCR4). We found that the moderate-sized lesion cavity, but not the large cavity caused by TBI was repaired via the transplantation of hUC-MSCsCXCR4 and activated astrocytes embedded in R-B-SPH scaffolds. The functional neural repair for TBI demonstrated in this study is mainly due to the transplantation system of double cells, hUC-MSCs and activated astrocytes. We believe that this novel cell transplantation system offers a promising treatment option for cell replacement therapy for TBI.
In this reach, we specifically linked RGIDKRHWNSQ, a functional peptide derived from BDNF, to the C-terminal of RADARADARADARADA (RADA16) to structure a functional self-assembling peptide hydrogel scaffold, RADA16-BDNF (R-B-SPH scaffold) for the better transplantation of the double cell unit. Also, the novel scaffold was used as cell-carrier for transplantation double cell unit (hUC-MSCs/astrocyte) for treating traumatic brain injury. The results of this study showing that R-B-SPH scaffold was pliancy and flexibility to fit the brain lesion cavity and promotes the outgrowth of axons and dendrites of the neurons derived from hUC-MSCs in vitro and in vivo, indicating the 3D R-B-SPH scaffold provided a suitable microenvironment for hUC-MSC survival, proliferation and differentiation. Also, our results showing the double-cells transplantation system (hUC-MSCs/astrocyte) may be a novel cell-based therapeutic strategy for neuroregeneration after TBI with potential value for clinical application.
Intense lasers can accelerate electrons to very high energy over a short distance. Such compact accelerators have several potential applications including fast ignition, high energy physics, and ...radiography. Among the various schemes of laser-based electron acceleration, vacuum laser acceleration has the merits of super-high acceleration gradient and great simplicity. Yet its realization has been difficult because injecting free electrons into the fast-oscillating laser field is not trivial. Here we demonstrate free-electron injection and subsequent vacuum laser acceleration of electrons up to 20 MeV using the relativistic transparency effect. When a high-contrast intense laser drives a thin solid foil, electrons from the dense opaque plasma are first accelerated to near-light speed by the standing laser wave in front of the solid foil and subsequently injected into the transmitted laser field as the opaque plasma becomes relativistically transparent. It is possible to further optimize the electron injection/acceleration by manipulating the laser polarization, incident angle, and temporal pulse shaping. Our result also sheds light on the fundamental relativistic transparency process, crucial for producing secondary particle and light sources.
Background and purpose
Elevated plasma total homocysteine level (tHcy) is associated with increased risk of dementia via increased white matter changes or reduction in cortical volume. Whether tHcy ...has an independent impact on regional perfusion and if it can predict a more rapid cognitive decline in mild Alzheimer dementia (AD) warrants investigation.
Methods
Eighty AD patients with a clinical dementia rating of 1 were enrolled. Their Cognitive Ability Screening Instrument (CASI) scores on enrolment and after 1 year of follow‐up as well as their perfusion index (PI) from single photon emission computed tomography upon enrolment were analyzed.
Results
In cross‐sectional analysis, elevated tHcy was associated with lower frontal PI independent of cerebrovascular risk factors (β = −0.35, P = 0.009). The CASI scores correlated with temporo‐parietal PI (Pearson r range 0.3–0.39, P < 0.01) but not with tHcy or frontal PI. By longitudinal analysis, only tHcy level was related to a more rapid cognitive decline (odds ratio for executive function score 1.82; odds ratio for total CASI score 1.74).
Conclusions
Cognitive performance in mild AD can be reflected by hypo‐perfusion of the temporo‐parietal region while frontal hypo‐perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.
Drastic variations of Earth's outer radiation belt electrons ultimately result from various competing source, loss, and transport processes, to which wave‐particle interactions are critically ...important. Using 15 spacecraft including NASA's Van Allen Probes, THEMIS, and SAMPEX missions and NOAA's GOES and POES constellations, we investigated the evolution of the outer belt during the strong geomagnetic storm of 30 September to 3 October 2012. This storm's main phase dropout exhibited enhanced losses to the atmosphere at L* < 4, where the phase space density (PSD) of multi‐MeV electrons dropped by over an order of magnitude in <4 h. Based on POES observations of precipitating >1 MeV electrons and energetic protons, SAMPEX >1 MeV electrons, and ground observations of band‐limited Pc1‐2 wave activity, we show that this sudden loss was consistent with pitch angle scattering by electromagnetic ion cyclotron waves in the dusk magnetic local time sector at 3 < L* < 4. At 4 < L* < 5, local acceleration was also active during the main and early recovery phases, when growing peaks in electron PSD were observed by both Van Allen Probes and THEMIS. This acceleration corresponded to the period when IMF Bz was southward, the AE index was >300 nT, and energetic electron injections and whistler‐mode chorus waves were observed throughout the inner magnetosphere for >12 h. After this period, Bz turned northward, and injections, chorus activity, and enhancements in PSD ceased. Overall, the outer belt was depleted by this storm. From the unprecedented level of observations available, we show direct evidence of the competitive nature of different wave‐particle interactions controlling relativistic electron fluxes in the outer radiation belt.
Key Points
WPIs compete as source and loss of relativistic outer belt electrons
EMIC waves can cause PA‐ and energy‐dependent loss at low L* during storms
Chorus waves can cause local acceleration of relativistic electrons
Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these ...effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic rather than genetic processes. However, epigenetic changes at a single gene promoter are unlikely to account for the range of outcomes and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care.
We examine here using high-density oligonucleotide array the state of DNA methylation, histone acetylation and gene expression in a 7 million base pair region of chromosome 18 containing the NR3C1 gene in the hippocampus of adult rats. Natural variations in maternal care are associated with coordinate epigenetic changes spanning over a hundred kilobase pairs. The adult offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends associated with higher transcriptional activity across many genes within the locus examined. Other genes in this region remain unchanged, indicating a clustered yet specific and patterned response. Interestingly, the chromosomal region containing the protocadherin-α, -β, and -γ (Pcdh) gene families implicated in synaptogenesis show the highest differential response to maternal care.
The results suggest for the first time that the epigenetic response to maternal care is coordinated in clusters across broad genomic areas. The data indicate that the epigenetic response to maternal care involves not only single candidate gene promoters but includes transcriptional and intragenic sequences, as well as those residing distantly from transcription start sites. These epigenetic and transcriptional profiles constitute the first tiling microarray data set exploring the relationship between epigenetic modifications and RNA expression in both protein coding and non-coding regions across a chromosomal locus in the mammalian brain.
Abstract Background and aims Hepatocellular carcinoma can be treated with heat-based therapies, especially radiofrequency ablation (RFA). However, RFA has limited efficacy and is quite expensive. We ...designed a new system using fine needles combined with an alternating magnetic field to generate hyperthermia for the treatment of hepatocellular carcinoma in a rat hepatoma model. Our aims are to assess the efficacy of our method and determine survival up to 30 days. Methods An N1-S1 cell line was inoculated into the livers of Sprague-Dawley rats, generating tumors after 14 days. The animals were randomized into 5 groups and treated after laparotomy either with normal saline (group I), iron oxide nanoparticles (group II), fine needles (group III), fine needles and iron oxide nanoparticles combined (group IV) or self-designed two-part needles placed under ultrasonographic guidance percutaneously (group V). Every rat was placed in an alternating magnetic field. The temperature in the treatment area was maintained between 55 and 60 °C. At day 30 after treatment, tumor volumes and mortality were assessed and histology samples were studied. Results Tumor volumes were significantly reduced and survival rate was prolonged in groups III, IV and V versus groups I and II ( P < 0.05). On pathological examination, groups III, IV and V presented obvious necrosis, apoptosis, calcifications and inflammatory changes in the treatment area. Conclusion Our study demonstrates that hyperthermia generated by fine stainless-steel needles combined with an alternating magnetic field effectively inhibits hepatoma growth in rats and prolongs their survival. Further, this method can be applied percutaneously under ultrasonographic guidance.
On 30 September 2012, a flux “dropout” occurred throughout Earth's outer electron radiation belt during the main phase of a strong geomagnetic storm. Using eight spacecraft from NASA's Time History ...of Events and Macroscale Interactions during Substorms (THEMIS) and Van Allen Probes missions and NOAA's Geostationary Operational Environmental Satellites constellation, we examined the full extent and timescales of the dropout based on particle energy, equatorial pitch angle, radial distance, and species. We calculated phase space densities of relativistic electrons, in adiabatic invariant coordinates, which revealed that loss processes during the dropout were > 90% effective throughout the majority of the outer belt and the plasmapause played a key role in limiting the spatial extent of the dropout. THEMIS and the Van Allen Probes observed telltale signatures of loss due to magnetopause shadowing and subsequent outward radial transport, including similar loss of energetic ring current ions. However, Van Allen Probes observations suggest that another loss process played a role for multi‐MeV electrons at lower L shells (L* < ~4).
Key Points
Dropout events can encompass the entire outer radiation belt
Dropouts can result in >90% losses and be a hard reset on the system
Loss at L > ~4 is dominated by MP shadowing and outward transport
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