105 research outputs found

    Heavy Higgs boson resonances and their decay into top quarks at the LHC

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    We investigate, within the type-II two-Higgs-doublet extension of the standard model (SM), the impact of heavy neutral Higgs boson resonances with unsuppressed Yukawa couplings to top quarks on top-quark pair production at the LHC at next-to-leading order (NLO) in the strong coupling constant. We take into account the resonant Higgs boson contributions, the non-resonant SM t<span style="text-decoration: overline">t</span> continuum and the interference of these two contributions. The NLO QCD corrections to heavy Higgs production and the interference contributions are calculated in the large top-quark mass (m<sub>t</sub>) limit, including an effective K-factor rescaling. Our evaluation of the QCD-Higgs interference is focused on the Higgs resonance region. Using representative CP-conserving as well as CP-violating parameter scenarios phenomenological results are presented for different observables

    Electroweak Top Couplings, Partial Compositeness and Top Partner Searches

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    Partial top quark compositeness is a crucial aspect of theories with strong electroweak symmetry breaking. Together with the heavy top partners that lift the top quark mass to its observed value, these theories predict correlated modifications of the top quark's electroweak couplings. Associated measurements therefore provide direct constraints on the ultraviolet structure of the underlying hypercolour dynamics. In this paper we employ a minimal version of top compositeness to discuss how measurements related to the top's electroweak gauge interactions can inform the potential composite nature of the TeV scale. In doing so, we identify the dominant factors that limit the BSM sensitivity. Extrapolating to a future 100 TeV hadron collider, we demonstrate that top quark measurements performed at highest precision can provide complementary information to resonance search by performing a representative resonant top partner search that specifically targets the correlated resonant electroweak top partner signatures.Comment: 14 pages, 5 figures, 1 table; v2: version accepted in PR

    Heavy Higgs boson production and decay into top quarks at the LHC

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    In this contribution we report on the calculation of the next-to-leading order (NLO) QCD corrections to the hadro-production of heavy neutral Higgs bosons and their decay into top-quark pairs within the type-II two-Higgs-doublet extension of the standard model (SM). We take into account the contributions from resonant Higgs boson production, the non-resonant SM t<span style="text-decoration: overline">t</span> background as well as the interference of these two contributions. The NLO corrections to the signal and interference contributions are calculated by applying the heavy top-quark mass (m<sub>t</sub>) limit including an effective rescaling. In our NLO calculation the QCD-Higgs interference is evaluated in the resonance region that provides the dominant part of the heavy Higgs-boson contributions. Evaluating representative CP-conserving and CP-violating parameter scenarios within the two-Higgs-doublet model (2HDM) we present results for different distributions and, in addition, for observables that depend on the top-quark spin

    Stress-Induced Changes In Extracellular Dopamine And Serotonin In The Medial Prefrontal Cortex And Dorsal Hippocampus Of Prenatally Malnourished Rats

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    Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The medial prefrontal cortex and dorsal hippocampus were chosen as two limbic forebrain regions involved in learning and memory, attention and the stress response. Extracellular 5-HT and dopamine were determined in the medial prefrontal cortex and dorsal hippocampus of adult male Sprague-Dawley rats using dual probe in vivo microdialysis. Basal extracellular 5-HT did not differ between malnourished and well-nourished controls in either the medial prefrontal cortex or the dorsal hippocampus. Basal extracellular dopamine was significantly decreased in the medial prefrontal cortex of malnourished animals. Restraint stress (20 m) produced a significant rise in extracellular dopamine in the medial prefrontal cortex of well-nourished rats but did not alter release in malnourished rats. In malnourished rats, stress produced an increase in 5-HT in the hippocampus, whereas stress produced a decrease in 5-HT in the hippocampus of well-nourished rats. These data demonstrate that prenatal protein malnutrition alters dopaminergic neurotransmission in the medial prefrontal cortex as well as altering the dopaminergic and serotonergic response to stress. These changes may provide part of the bases for alterations in malnourished animals’ response to stress

    Electroweak top couplings, partial compositeness, and top partner

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    Partial top quark compositeness is a crucial aspect of theories with strong electroweak symmetry breaking. Together with the heavy top partners that lift the top quark mass to its observed value, these theories predict correlated modifications of the top quark’s electroweak couplings. Associated measurements therefore provide direct constraints on the ultraviolet structure of the underlying hypercolour dynamics. In this paper we employ a minimal version of top compositeness to discuss how measurements related to the top’s electroweak gauge interactions can inform the potential composite nature of the TeV scale. In doing so, we identify the dominant factors that limit the BSM sensitivity. Extrapolating to a future 100 TeV hadron collider, we demonstrate that top quark measurements performed at highest precision can provide additional information to resonance search by performing a representative resonant top partner search that specifically targets the correlated resonant electroweak top partner signatures

    Stress-induced changes in extracellular dopamine and serotonin in the medial prefrontal cortex and dorsal hippocampus of prenatally malnourished rats. Brain Res

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    Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment, we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The medial prefrontal cortex and dorsal hippocampus were chosen as two limbic forebrain regions involved in learning and memory, attention and the stress response. Extracellular 5-HT and dopamine were determined in the medial prefrontal cortex and dorsal hippocampus of adult male Sprague-Dawley rats using dual probe in vivo microdialysis. Basal extracellular 5-HT did not differ between malnourished and well-nourished controls in either the medial prefrontal cortex or the dorsal hippocampus. Basal extracellular dopamine was significantly decreased in the medial prefrontal cortex of malnourished animals. Restraint stress (20 m) produced a significant rise in extracellular dopamine in the medial prefrontal cortex of well-nourished rats but did not alter release in malnourished rats. In malnourished rats, stress produced an increase in 5-HT in the hippocampus, whereas stress produced a decrease in 5-HT in the hippocampus of well-nourished rats. These data demonstrate that prenatal protein malnutrition alters dopaminergic neurotransmission in the medial prefrontal cortex as well as alters the dopaminergic and serotonergic response to stress. These changes may provide part of the bases for alterations in malnourished animals' response to stress. Introduction Prenatal protein malnutrition affects a significant portion of the world's population. Our group has attempted to understand the consequences of malnutrition on the development of the brain in a rat model of prenatal protein malnutrition which exposes rats in utero to a low (6%) casein die

    Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma

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    <p>Abstract</p> <p>Background</p> <p>Lung cancer is the number one cancer killer of both men and women in the United States. Three quarters of lung cancer patients are diagnosed with regionally or distantly disseminated disease; their 5-year survival is only 15%. DNA hypermethylation at promoter CpG islands shows great promise as a cancer-specific marker that would complement visual lung cancer screening tools such as spiral CT, improving early detection. In lung cancer patients, such hypermethylation is detectable in a variety of samples ranging from tumor material to blood and sputum. To date the penetrance of DNA methylation at any single locus has been too low to provide great clinical sensitivity. We used the real-time PCR-based method MethyLight to examine DNA methylation quantitatively at twenty-eight loci in 51 primary human lung adenocarcinomas, 38 adjacent non-tumor lung samples, and 11 lung samples from non-lung cancer patients.</p> <p>Results</p> <p>We identified thirteen loci showing significant differential DNA methylation levels between tumor and non-tumor lung; eight of these show highly significant hypermethylation in adenocarcinoma: CDH13, CDKN2A EX2, CDX2, HOXA1, OPCML, RASSF1, SFPR1, and TWIST1 (p-value << 0.0001). Using the current tissue collection and 5-fold cross validation, the four most significant loci (CDKN2A EX2, CDX2, HOXA1 and OPCML) individually distinguish lung adenocarcinoma from non-cancer lung with a sensitivity of 67–86% and specificity of 74–82%. DNA methylation of these loci did not differ significantly based on gender, race, age or tumor stage, indicating their wide applicability as potential lung adenocarcinoma markers. We applied random forests to determine a good classifier based on a subset of our loci and determined that combined use of the same four top markers allows identification of lung cancer tissue from non-lung cancer tissue with 94% sensitivity and 90% specificity.</p> <p>Conclusion</p> <p>The identification of eight CpG island loci showing highly significant hypermethylation in lung adenocarcinoma provides strong candidates for evaluation in patient remote media such as plasma and sputum. The four most highly ranked loci, CDKN2A EX2, CDX2, HOXA1 and OPCML, which show significant DNA methylation even in stage IA tumor samples, merit further investigation as some of the most promising lung adenocarcinoma markers identified to date.</p

    Prenatal Protein Malnutrition Leads to Hemispheric Differences in the Extracellular Concentrations of Norepinephrine, Dopamine and Serotonin in the Medial Prefrontal Cortex of Adult Rats

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    Exposure to prenatal protein malnutrition (PPM) leads to a reprogramming of the brain, altering executive functions involving the prefrontal cortex (PFC). In this study we used in vivo microdialysis to assess the effects of PPM on extracellular concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) bilaterally in the ventral portion of the medial prefrontal cortex (vmPFC; ventral prelimbic and infralimbic cortices) of adult Long-Evans rats. Female Long-Evans rats were fed either a low protein (6%) or adequate protein diet (25%) prior to mating and throughout pregnancy. At birth, all litters were culled and fostered to dams fed a 25% (adequate) protein diet. At 120 days of age, 2 mm microdialysis probes were placed into left and right vmPFC. Basal extracellular concentrations of NE, DA, and 5-HT were determined over a 1-h period using HPLC. In rats exposed to PPM there was a decrease in extracellular concentrations of NE and DA in the right vmPFC and an increase in the extracellular concentration of 5-HT in the left vmPFC compared to controls (prenatally malnourished: N = 10, well-nourished: N = 20). Assessment of the cerebral laterality of extracellular neurotransmitters in the vmPFC showed that prenatally malnourished animals had a significant shift in laterality from the right to the left hemisphere for NE and DA but not for serotonin. In a related study, these animals showed cognitive inflexibility in an attentional task. In animals in the current study, NE levels in the right vmPFC of well-nourished animals correlated positively with performance in an attention task, while 5-HT in the left vmPFC of well-nourished rats correlated negatively with performance. These data, in addition to previously published studies, suggest a long-term reprogramming of the vmPFC in rats exposed to PPM which may contribute to attention deficits observed in adult animals exposed to PPM

    Femtosecond X-ray emission study of the spin cross-over dynamics in haem proteins

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    In haemoglobin (consisting of four globular myoglobin-like subunits), the change from the low-spin (LS) hexacoordinated haem to the high spin (HS) pentacoordinated domed form upon ligand detachment and the reverse process upon ligand binding, represent the transition states that ultimately drive the respiratory function. Visible-ultraviolet light has long been used to mimic the ligand release from the haem by photodissociation, while its recombination was monitored using time-resolved infrared to ultraviolet spectroscopic tools. However, these are neither element- nor spin-sensitive. Here we investigate the transition state in the case of Myoglobin-NO (MbNO) using femtosecond Fe Kalpha and Kbeta non-resonant X-ray emission spectroscopy (XES) at an X-ray free-electron laser upon photolysis of the Fe-NO bond. We find that the photoinduced change from the LS (S = 1/2) MbNO to the HS (S = 2) deoxy-myoglobin (deoxyMb) haem occurs in ca. 800 fs, and that it proceeds via an intermediate (S = 1) spin state. The XES observables also show that upon NO recombination to deoxyMb, the return to the planar MbNO ground state is an electronic relaxation from HS to LS taking place in ca. 30 ps. Thus, the entire ligand dissociation-recombination cycle in MbNO is a spin cross-over followed by a reverse spin cross-over process
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