Search for Free Fractional Electric Charge Elementary Particles

We have carried out a direct search in bulk matter for free fractional electric charge elementary particles using the largest mass single sample ever studied - about 17.4 mg of silicone oil. The search used an improved and highly automated Millikan oil drop technique. No evidence for fractional charge particles was found. The concentration of particles with fractional charge more than 0.16e (e being the magnitude of the electron charge) from the nearest integer charge is less than $4.71\times10^{-22}$ particles per nucleon with 95% confidence.Comment: 10 pages,LaTeX, 4 PS figures, submitted to PR

A New Method for Searching for Free Fractional Charge Particles in Bulk Matter

We present a new experimental method for searching for free fractional charge in bulk matter; this new method derives from the traditional Millikan liquid drop method, but allows the use of much larger drops, 20 to 100 mm in diameter, compared to the traditional method that uses drops less than 15 mm in diameter. These larger drops provide the substantial advantage that it is then much easier to consistently generate drops containing liquid suspensions of powdered meteorites and other special minerals. These materials are of great importance in bulk searches for fractional charge particles that may have been produced in the early universe.Comment: 17 pages, 5 figures in a singl PDF file (created from WORD Doc.). Submitted to Review of Scientific Instrument

Reactive oxygen species induce virus-independent MAVS-oligomerization in systemic lupus erythematosus

The increased expression of genes induced by type I interferon (IFN) is characteristic of viral infections and systemic lupus erythematosus (SLE). We showed that mitochondrial antiviral signaling (MAVS) protein, which normally forms a complex with retinoic acid gene I (RIG-I)–like helicases during viral infection, was activated by oxidative stress independently of RIG-I helicases. We found that chemically generated oxidative stress stimulated the formation of MAVS oligomers, which led to mitochondrial hyperpolarization and decreased adenosine triphosphate production and spare respiratory capacity, responses that were not observed in similarly treated cells lacking MAVS. Peripheral blood lymphocytes of SLE patients also showed spontaneous MAVS oligomerization that correlated with the increased secretion of type I IFN and mitochondrial oxidative stress. Furthermore, inhibition of mitochondrial reactive oxygen species (ROS) by the mitochondria-targeted antioxidant MitoQ prevented MAVS oligomerization and type I IFN production. ROS-dependent MAVS oligomerization and type I IFN production were reduced in cells expressing the MAVS-C79F variant, which occurs in 30% of sub-Saharan Africans and is linked with reduced type I IFN secretion and milder disease in SLE patients. Patients expressing the MAVS-C79F variant also had reduced amounts of oligomerized MAVS in their plasma compared to healthy controls. Together, our findings suggest that oxidative stress–induced MAVS oligomerization in SLE patients may contribute to the type I IFN signature that is characteristic of this syndrome

Measurement of Dielectric Suppression of Bremsstrahlung

In 1953, Ter-Mikaelian predicted that the bremsstrahlung of low energy photons in a medium is suppressed because of interactions between the produced photon and the electrons in the medium. This suppression occurs because the emission takes place over on a long distance scale, allowing for destructive interference between different instantaneous photon emission amplitudes. We present here measurements of bremsstrahlung cross sections of 200 keV to 20 MeV photons produced by 8 and 25 GeV electrons in carbon and gold targets. Our data shows that dielectric suppression occurs at the predicted level, reducing the cross section up to 75 percent in our data.Comment: 11 pages, format is postscript file, gzip-ed, uuencode-e

Big-Bang Nucleosynthesis and Hadronic Decay of Long-Lived Massive Particles

We study the big-bang nucleosynthesis (BBN) with the long-lived exotic particle, called X. If the lifetime of X is longer than \sim 0.1 sec, its decay may cause non-thermal nuclear reactions during or after the BBN, altering the predictions of the standard BBN scenario. We pay particular attention to its hadronic decay modes and calculate the primordial abundances of the light elements. Using the result, we derive constraints on the primordial abundance of X. Compared to the previous studies, we have improved the following points in our analysis: The JETSET 7.4 Monte Carlo event generator is used to calculate the spectrum of hadrons produced by the decay of X; The evolution of the hadronic shower is studied taking account of the details of the energy-loss processes of the nuclei in the thermal bath; We have used the most recent observational constraints on the primordial abundances of the light elements; In order to estimate the uncertainties, we have performed the Monte Carlo simulation which includes the experimental errors of the cross sections and transfered energies. We will see that the non-thermal productions of D, He3, He4 and Li6 provide stringent upper bounds on the primordial abundance of late-decaying particle, in particular when the hadronic branching ratio of X is sizable. We apply our results to the gravitino problem, and obtain upper bound on the reheating temperature after inflation.Comment: 94 pages, 49 figures, to appear in Phys. Rev. D. This is a full length paper of the preprint astro-ph/040249

Narrowing the window for millicharged particles by CMB anisotropy

We calculate the cosmic microwave background (CMB) anisotropy spectrum in models with millicharged particles of electric charge q\sim 10^{-6}-10^{-1} in units of electron charge. We find that a large region of the parameter space for the millicharged particles exists where their effect on the CMB spectrum is similar to the effect of baryons. Using WMAP data on the CMB anisotropy and assuming Big Bang nucleosynthesis value for the baryon abundance we find that only a small fraction of cold dark matter, Omega_{mcp}h_0^2 < 0.007 (at 95% CL), may consists of millicharged particles with the parameters (charge and mass) from this region. This bound significantly narrows the allowed range of the parameters of millicharged particles. In models without paraphoton millicharged particles are now excluded as a dark matter candidate. We also speculate that recent observation of 511 keV gamma-rays from the Galactic bulge may be an indication that a (small) fraction of CDM is comprised of the millicharged particles.Comment: 10 pages, 3 figures; v2: journal version, references adde

The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer's disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen's kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen's kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II-III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies

Searches for Stable Strangelets in Ordinary Matter: Overview and a Recent Example

Our knowledge on the possible existence in nature of stable exotic particles depends solely upon experimental observation. Guided by this general principle and motivated by theoretical hypotheses on the existence of stable particles of strange quark matter, a variety of experimental searches have been performed. We provide an introduction to the theoretical hypotheses, an overview of the past searches, and a more detailed description of a recent search for helium-like strangelets in the Earth's atmosphere using a sensitive laser spectroscopy method

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro

Charged Scalar Particles and τ\tau Leptonic Decay

Charged scalar particles introduced in some extensions of the standard model can induce $\tau$ leptonic decay at tree level. We find that with some charged SU(2)-singlet scalar particles, like ones introduced in Zee-type models, $\tau$ leptonic decay width is always smaller than what is predicted by the standard model, therefore they may offer a natural solution to $\tau$ decay puzzle. To be more specific, we examine some Zee-type models in detail to see if at the same time they are acceptable in particle physics, cosmology and astrophysics. It is shown that $\tau$ decay data do put some constrains on these models.Comment: ICTP Report No. IC/93/31, 12 pages, Latex, one figure is not included, it is available upon deman