We report the observation of a narrow charmoniumlike state produced in the exclusive decay process B+/--->K+/-pi(+)pi(-)J/psi. This state, which decays into pi(+)pi(-)J/psi, has a mass of ...3872.0+/-0.6(stat)+/-0.5(syst) MeV, a value that is very near the M(D0)+M(D(*0)) mass threshold. The results are based on an analysis of 152M B-Bmacr; events collected at the Upsilon(4S) resonance in the Belle detector at the KEKB collider. The signal has a statistical significance that is in excess of 10sigma.
Beam tests of a large-scale TORCH time-of-flight demonstrator Hancock, T.H.; Bhasin, S.; Blake, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2020, Letnik:
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The TORCH time-of-flight detector is designed to provide particle identification in the momentum range 2−10GeV∕c over large areas. The detector exploits prompt Cherenkov light produced by charged ...particles traversing a 10mm thick quartz plate. The photons propagate via total internal reflection and are focused onto a detector plane comprising position-sensitive Micro-Channel Plate Photo-Multiplier Tubes (MCP-PMT) detectors. The goal is to achieve a single-photon timing resolution of 70ps, giving a timing precision of 15ps per charged particle by combining the information from around 30 detected photons. The MCP-PMT detectors have been developed with a commercial partner (Photek Ltd, UK), leading to the delivery of a square tube of active area 53×53mm2 with a granularity of 8×128pixels equivalent. A large-scale demonstrator of TORCH, having a quartz plate of dimensions 660×1250×10mm3 and read out by a pair of MCP-PMTs with custom readout electronics, has been verified in a test beam campaign at the CERN PS. Preliminary results indicate that the required performance is close to being achieved. The anticipated performance of a full-scale TORCH detector at the LHCb experiment is presented.
TORCH is a time-of-flight detector designed to perform particle identification over the momentum range 2–10 GeV/c for a 10 m flight path. The detector exploits prompt Cherenkov light produced by ...charged particles traversing a quartz plate of 10mm thickness. Photons are then trapped by total internal reflection and directed onto a detector plane instrumented with customised position-sensitive Micro-Channel Plate Photo-Multiplier Tube (MCP-PMT) detectors. A single-photon timing resolution of 70ps is targeted to achieve the desired separation of pions and kaons, with an expectation of around 30 detected photons per track. Studies of the performance of a small-scale TORCH demonstrator with a radiator of dimensions 120×350×10mm3 have been performed in two test-beam campaigns during November 2017 and June 2018. Single-photon time resolutions ranging from 104.3ps to 114.8ps and 83.8ps to 112.7ps have been achieved for MCP-PMTs with granularity 4 × 64 and 8 × 64 pixels, respectively. Photon yields are measured to be within ∼10% and ∼30% of simulation, respectively. Finally, the outlook for future work with planned improvements is presented.
Neurogenesis requires negative regulation through differentiation of progenitors or their programmed cell death (PCD). Growth regulation is particularly important in the postnatal cerebellum, where ...excessive progenitor proliferation promotes medulloblastoma, the most common malignant brain tumor in children. We present evidence that PCD operates alongside differentiation to regulate cerebellar granule neuron progenitors (CGNPs) and to prevent medulloblastoma. Here, we show that genetic deletion of pro-apoptotic Bax disrupts regulation of cerebellar neurogenesis and promotes medulloblastoma formation. In Bax(-/-) mice, the period of neurogenesis was extended into the third week of postnatal life, and ectopic neurons and progenitors collected in the molecular layer of the cerebellum and adjacent tectum. Importantly, genetic deletion of Bax in medulloblastoma-prone ND2:SmoA1 transgenic mice greatly accelerated tumorigenesis. Bax-deficient medulloblastomas exhibited strikingly distinct pathology, with reduced apoptosis, increased neural differentiation and tectal migration. Comparing Bax(+/+) and Bax(-/-) medulloblastomas, we were able to identify upregulation of Bcl-2 and nuclear exclusion of p27 as tumorigenic changes that are required to mitigate the tumor suppressive effect of Bax. Studies on human tumors confirmed the importance of modulating Bax in medulloblastoma pathogenesis. Our results demonstrate that Bax-dependent apoptosis regulates postnatal cerebellar neurogenesis, suppresses medulloblastoma formation and imposes selective pressure on tumors that form. Functional resistance to Bax-mediated apoptosis, required for medulloblastoma tumorigenesis, may be a tumor-specific vulnerability to be exploited for therapeutic benefit.
The TORCH time-of-flight detector is designed to provide a 15 ps timing resolution for charged particles, resulting in
π
/K particle identification up to 10 GeV/c momentum over a 10 m flight path. ...Cherenkov photons, produced in a quartz plate of 10 mm thickness, are focused onto an array of micro-channel plate photomultipliers (MCP-PMTs) which measure the photon arrival times and spatial positions. A half-scale (660 × 1250 × 10 mm
3
) TORCH demonstrator module has been tested in an 8 GeV/c mixed proton-pion beam at CERN. Customised square MCP-PMTs of active area 53 × 53 mm
2
and granularity 64 × 64 pixels have been employed, which have been developed in collaboration with an industrial partner. The single-photon timing performance and photon yields have been measured as a function of beam position in the radiator, giving measurements which are consistent with expectations. The expected performance of TORCH for high luminosity running of the LHCb Upgrade II has been simulated.
Correction to: Oncogene (2013) 32, 2304–2314; doi:10.1038/onc. 2012.248; published online 18 June 2012. Since the publication of the above paper, the author listed as C Ryan Miller has requested that ...the listing of his name be changed to CR Miller.
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is silenced by promoter methylation in many types of tumors, yet ASC's role in most cancers remains unknown. ...Here, we show that ASC is highly expressed in a model of medulloblastoma, the most common malignant pediatric brain cancer; ASC is also expressed in human medulloblastomas. Importantly, while ASC deficiency did not affect normal cerebellar development, ASC knockout mice on the Smoothened (ND2:SmoA1) transgenic model of medulloblastoma exhibited a profound reduction in medulloblastoma incidence and a delayed tumor onset. A similar decrease in tumorigenesis with ASC deficiency was also seen in the hGFAP-Cre:SmoM2 mouse model of medulloblastoma. Interestingly, hyperproliferation of the external granule layer (EGL) was comparable at P20 in both wild-type and ASC-deficient SmoA1 mice. However, while the apoptosis and differentiation markers remained unchanged at this age, proliferation makers were decreased, and the EGL was reduced in thickness and area by P60. This reduction in proliferation with ASC deficiency was also seen in isolated SmoA1 cerebellar granule precursor cells in vitro, indicating that the effect of ASC deletion on proliferation was cell autonomous. Interestingly, ASC-deficient SmoA1 cerebella exhibited disrupted expression of genes in the transforming growth factor-β pathway and increased level of nuclear Smad3. Taken together, these results demonstrate an unexpected role for ASC in Sonic hedgehog-driven medulloblastoma tumorigenesis, thus identifying ASC as a promising novel target for antitumor therapy.
Background
Central nervous system (CNS) germ cell tumors account for 3 % of all pediatric brain tumors in the USA. Presenting symptoms are typically location based with pineal tumors presenting with ...obstructive hydrocephalus and suprasellar tumors with hypothalamic/pituitary dysfunction and ophthalmologic abnormalities. Psychiatric manifestations such as psychosis and behavioral changes are atypical presentations of CNS germ cell tumors, with only 11 previously reported cases.
Methods
This is a retrospective case series describing patients with CNS germ cell tumors with an atypical presentation including psychiatric manifestations. Information regarding clinical presentation, treatment course, and outcome were obtained.
Results
We report seven patients who presented with psychiatric symptoms consisting of psychomotor delay as well as behavioral and mood changes. Six of the seven patients were diagnosed ≥6 months after onset of psychiatric symptoms. All of the seven are alive but five continue to have neurologic and psychiatric issues post treatment.
Conclusions
Atypical presentations of CNS germ cell tumors can delay diagnosis and treatment and may be secondary to atypical locations as well as endocrine dysfunction manifesting as psychiatric symptoms. Delayed diagnosis did not appear to affect survival but earlier diagnosis may potentially be associated with better neurologic and psychiatric outcome. Patients who present with these symptoms and atypical neuroimaging should have a thorough evaluation for CNS germ cell tumors including serum and CSF markers. Clinicians should be aware of these less common presentations to aid in prompt diagnosis and treatment.
The RNA polymerase II core promoter is a critical yet often overlooked component in the transcription process. The core promoter is defined as the stretch of DNA, which encompasses the RNA start site ...and is typically approx. 40-50 nt in length, that directs the initiation of gene transcription. In the past, it has been generally presumed that core promoters are general in function and that transcription initiation occurs via a common shared mechanism. Recent studies have revealed, however, that there is considerable diversity in core promoter structure and function. There are a number of DNA elements that contribute to core promoter activity, and the specific properties of a given core promoter are dictated by the presence or absence of these core promoter motifs. The known core promoter elements include the TATA box, Inr (initiator), BRE(u) {BRE TFIIB (transcription factor for RNA polymerase IIB) recognition element upstream of the TATA box} and BRE(d) (BRE downstream of the TATA box), MTE (motif ten element), DCE (downstream core element) and DPE (downstream core promoter element). In this paper, we will provide some perspectives on current and future issues that pertain to the RNA polymerase II core promoter.
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