Large experimental programmes in the fields of nuclear and particle physics search for evidence of physics beyond that explained by current theories. The observation of the Higgs boson completed the ...set of particles predicted by the standard model, which currently provides the best description of fundamental particles and forces. However, this theory's limitations include a failure to predict fundamental parameters, such as the mass of the Higgs boson, and the inability to account for dark matter and energy, gravity, and the matter-antimatter asymmetry in the Universe, among other phenomena. These limitations have inspired searches for physics beyond the standard model in the post-Higgs era through the direct production of additional particles at high-energy accelerators, which have so far been unsuccessful. Examples include searches for supersymmetric particles, which connect bosons (integer-spin particles) with fermions (half-integer-spin particles), and for leptoquarks, which mix the fundamental quarks with leptons. Alternatively, indirect searches using precise measurements of well predicted standard-model observables allow highly targeted alternative tests for physics beyond the standard model because they can reach mass and energy scales beyond those directly accessible by today's high-energy accelerators. Such an indirect search aims to determine the weak charge of the proton, which defines the strength of the proton's interaction with other particles via the well known neutral electroweak force. Because parity symmetry (invariance under the spatial inversion (x, y, z) → (-x, -y, -z)) is violated only in the weak interaction, it provides a tool with which to isolate the weak interaction and thus to measure the proton's weak charge
. Here we report the value 0.0719 ± 0.0045, where the uncertainty is one standard deviation, derived from our measured parity-violating asymmetry in the scattering of polarized electrons on protons, which is -226.5 ± 9.3 parts per billion (the uncertainty is one standard deviation). Our value for the proton's weak charge is in excellent agreement with the standard model
and sets multi-teraelectronvolt-scale constraints on any semi-leptonic parity-violating physics not described within the standard model. Our results show that precision parity-violating measurements enable searches for physics beyond the standard model that can compete with direct searches at high-energy accelerators and, together with astronomical observations, can provide fertile approaches to probing higher mass scales.
A beam-normal single-spin asymmetry generated in the scattering of transversely polarized electrons from unpolarized nucleons is an observable related to the imaginary part of the two-photon exchange ...process. We report a 2% precision measurement of the beam-normal single-spin asymmetry in elastic electron-proton scattering with a mean scattering angle of θlab=7.9° and a mean energy of 1.149 GeV. The asymmetry result is Bn=−5.194±0.067(stat)±0.082 (syst) ppm. This is the most precise measurement of this quantity available to date and therefore provides a stringent test of two-photon exchange models at far-forward scattering angles (θlab→0) where they should be most reliable.
Meningioma is the most frequent tumor of neuroectodermal origin in humans. It is usually benign. Only a minority of cases shows progression to an anaplastic tumor (WHO grade II and III). Meningioma ...is generally a sporadic tumor. Multiple and familial cases are rare and mostly associated with (hereditary) neurofibromatosis 2 (NF2). Meningiomas show an unexpectedly high recurrence rate. Also, completely removed low-grade tumors can recur. Recurrence and multiplicity are correlated with the formation of a peritumoral edema. On the cytogenetic level, meningioma is the best-studied tumor in humans. Grade I tumors show either uniform monosomy 22 or a diploid karyotype. The majority of high-grade, but only a minority of low-grade, meningiomas show loss of merlin, a cytoskeleton-cytoplasm-linker protein. Merlin is the product of the NF2 gene located on chromosome 22. A second tumor suppressor gene on chromosome 22 has not yet been detected. In contrast to other solid tumors, progression of meningiomas is correlated with increasing hypodiploidy, showing characteristic clonal evolutions that mostly include chromosomes 14, 18, and 19 and, more rarely, 6 and 10. Structural aberrations are infrequent, except for the loss of the short arm of chromosome 1, which appears to be the decisive step for anaplastic growth. Comparative histochemical and molecular cytogenetic studies point to the alkaline phosphatase gene (ALPL, liver-bone-kidney type) located on 1p36.1-->p34 as a candidate tumor suppressor gene. A model is proposed that tries to explain - with a minimum number of essential steps - the origin, progression, infiltration, and recurrence of meningiomas.
Abstract
During lactation, large amounts of calcium are exported from the mammary gland into milk to ensure skeletal growth of the offspring. Recent studies revealed that serotonin (5-HT) is ...essential to stimulate skeletal calcium resorption for milk synthesis. Our objective was to explore the correlation between circulating 5-HT and serum calcium and parathyroid hormone-related protein (PTHrP) concentrations around parturition in dairy goats. We also investigated the effect of 5-HT on PTHrP expression in cultured primary goat mammary epithelial cells (GMEC). Blood samples of multiparous Guanzhong dairy goats were collected on day −5 to 3 postpartum for analysis of serum concentrations of calcium, 5-HT, and PTHrP. Results revealed that from day −3 to 0 postpartum serum calcium and 5-HT concentrations decreased progressively, but serum PTHrP concentration only had a sharp drop in the postpartum period sampled. Correlation analysis of circulating 5-HT and serum calcium and PTHrP concentrations on day 1 and 2 postpartum revealed that low serum 5-HT concentration was positively correlated with serum total calcium or PTHrP concentration. By knocking down tryptophan hydroxylase-1 (TPH1) or adding 5-hydroxytryptophan (5-HTP) to decrease or increase the levels of 5-HT in GMEC, we observed that 5-HTP increased PTHrP expression in a dose-dependent manner and siTPH1 decreased PTHrP protein expression. Furthermore, 5-HT increased mRNA abundance of calcium-sensing receptor (CaSR) in a dose-dependent manner and decreased the expression of plasma membrane Ca2+ ATPase-1 (PMCA1). Taken together, 5-HT seems to induce PTHrP expression in goat mammary cells during and after parturition. These findings suggest that increasing 5-HT biosynthesis could be a potential therapeutic target for prevention of hypocalcemia in dairy goats.
Tierling S, Souren NY, Reither S, Zang KD, Meng‐Hentschel J, Leitner D, Oehl‐Jaschkowitz B, Walter J. DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for ...Beckwith–Wiedemann syndrome.
Beckwith–Wiedemann syndrome (BWS) is one of the most prevalent congenital disorders predominantly caused by epigenetic alterations. Here we present an extensive case study of a monozygotic monochorionic male twin pair discordant for BWS. Our analysis allows to correlate BWS symptoms, like a protruding tongue, indented ears and transient neonatal hypoglycaemia, to an abnormal methylation at the KvDMR1. DNAs extracted from peripheral blood, skin fibroblasts, saliva and buccal swab of both twins, their sister and parents were analysed at 11 differentially methylated regions (DMRs) including all four relevant DMRs of the BWS region. The KvDMR1 was exclusively found to be hypomethylated in all cell types of the affected BWS twin, while the unaffected twin and the relatives showed normal methylation in fibroblasts, buccal swab and saliva DNA. Interestingly, the twins share a common blood‐specific hypomethylation phenotype most probably caused by a feto‐fetal transfusion between both twins. Because microsatellite analysis furthermore revealed a normal biparental karyotype for chromosome 11, our results point to an exclusive correlation of the observed BWS symptoms to locally restricted epimutations at the KvDMR1 of the maternal chromosome.
The goal of this study was to determine whether in meningiomas cytogenetic findings are suitable as a predictive parameter relevant to prognosis.
Between 1992 and 1998 at the Department of ...Neurosurgery, Saarland University, 198 patients underwent surgery to resect meningiomas. The meningiomas were investigated cytogenetically and the patients were followed up for a mean period of 33 months. On the basis of the cytogenetic findings, the meningiomas were subdivided into four groups: Group 0 meningiomas displayed a normal diploid chromosome set; Group 1 tumors were found to have monosomy 22 as the sole cytogenetic aberration; Group 2 tumors were markedly hypodiploid meningiomas with loss of additional autosomes in addition to monosomy 22; and Group 3 meningiomas had deletions of the short arm of a chromosome 1, as well as additional chromosomal aberrations including loss of one chromosome 22. One hundred ninety-eight patients in whom tumor resections were determined to be Simpson Grade I or II could be followed up after complete tumor extirpation. In 20 patients, one or several recurrences were documented during the period of observation. The tumors were classified according to their different, but mostly uniform chromosomal aberrations. Recurrences were found in six (4.3%) of 139 tumors in Groups 0 and 1 and in two (10.5%) of 19 tumors in Group 2; the highest rate of recurrence was found in 12 (30%) of 40 tumors in Group 3. This supports the notion that the deletion of the short arm of one chromosome 1 is an important prognostic factor in meningiomas. The results of this study document a significant correlation between histological grade (p < 0.0001), location (p < 0.0001), and recurrences of meningiomas (p < 0.0001) (significance determined using chi-square tests).
The cytogenetic classification of meningiomas provides a significant contribution to the predictability of tumor recurrence and is, therefore, a valuable criterion for the neurosurgeon's postoperative management protocol.
By screening a meningioma expression library with autologous serum we identified four cDNA clones representing a novel gene with striking homology to Caenorhabditis elegans hyaluronidase as indicated ...by BLASTP analysis. In humans hyaluronidase has been implicated in cancer development and three human genes are known to encode proteins with hyaluronidase activity. None of the human genes, however, showed any homology at the nucleotide or amino acid sequence level to the newly isolated antigen we termed meningioma expressed antigen 5 (MGEA5). Somatic cell hybrid mapping and fluorescence in situ hybridization mapped the gene for MGEA5 to chromosomal band 10q24.1–q24.3. Reverse transcription (RT)-PCR and northern blot hybridization revealed expression of the gene encoding MGEA5 in several meningioma and additional human tissues. Expression analysis also indicated an alternative splicing event giving rise to a shorter and altered transcript termed MGEA5s. The expression of MGEA5 and MGEA5s as fusion proteins revealed an approximate molecular weight of 92 and 54 kDa, respectively. Using heterologous sera we found antibodies against MGEA5s in five out of 23 meningioma patients, whereas no immune reaction was detected in 12 control sera from healthy individuals. Confirmation of hyaluron-idase activity was independently achieved by turbido-metric analysis and a gel matrix assay. A model for involvement of the novel hyaluronidase gene in meningioma development is proposed.
The detail fatigue rating (DFR) value of friction stir welded (FSW) lap joints for dissimilar AA7150-AA2524 aluminum alloy was experimentally investigated. The metallographic analysis was carried out ...on by optical microscope (OM). Fatigue fractography was observed under scanning electron microscope (SEM). The results indicate that DFR value of AA7150-AA2524 FSW lap joints is 191.54MPa. There is no distinct different boundary between HAZ and BM of the upper AA7150 sheet. The grains in the upper NZ of AA7150 are coarser than those in the bottom NZ of AA2524. Fracture morphologies shows that lots of hook defects in the FSW lap joint. Fractography indicates that fatigue crack is initiated from the AA2524 bottom surface around the weld center, where weak-bonding defects can be seen. The hook defects and weak-bonding defects have obvious influence on the fatigue property of friction stir welding lap joints, which seriously reduce the fatigue strength.
The serine/threonine kinase 15 (STK15) at chromosome 20q13.2 is frequently shown to be amplified and overexpressed in several human cancers. STK15 has been reported to act as a cell cycle regulator ...and its overexpression induces centrosome amplification and aneuploidy. Recently we showed that STK15 even plays a role in human malignant brain tumours and we described an amplification of the gene in 31% of the investigated gliomas. In this study we scrutinized the correlation of increased STK15 on DNA and mRNA levels in gliomas of different histological grades. Southern blotting confirmed the amplification frequency of the STK15 gene, which had been previously detected by comparative PCR. In total, DNA gains were found in 26% of the investigated gliomas. Interestingly, we detected overexpression of STK15 mRNA in 60% of the analyzed brain tumours. The elevated expression does not strongly correlate with gains on DNA level, but all cases with an amplification of the STK15 gene display overexpression. Gains of the STK15 gene seem to occur irrespectively of the histological grades of the tumours, so that STK15 probably is not a progression associated factor. Amplification and overexpression of the kinase rather represent a primary alteration in human gliomas, which could play an important role as an early event in all glioma subtypes.
The North Qaidam and South Altyn terranes extend approximately 1000 km across the northern Tibetan Plateau, and five localities preserve evidence of Early Paleozoic high-pressure (HP) or ...ultrahigh-pressure (UHP) metamorphism, including the presence of coesite, coesite pseudomorphs, and diamond. A review of the geology, petrology, and geochronology collected over the past 10 years since these localities were discovered supports a correlation of the North Qaidam and South Altyn terranes, offset 350-400 km across the Altyn Tagh fault. Geochronology interpreted to reflect eclogite-facies metamorphism yields ages between 500 and 420 Ma; detailed geochronology from one locality supports a protracted (tens of m.y.) history of HP/UHP metamorphism. Rock associations and geochronology support a passive-margin origin for the protolith of the HP/UHP rocks, which received sediments from a Proterozoic-Late Archean source, and was intruded by Neoproterozoic granites derived from crustal melting.
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