An unusually massive stellar black hole in the Galaxy

Here we report a measurement of the orbital period and mass function of GRS 1915+105 which allow us to deduce a mass of 14 +- 4 solar masses for its black hole. This large mass provides a challenge for black hole formation scenarios in binaries, since black holes with masses above 5-7 solar masses are hard to explain. Also, the mass estimate allows us to understand the unique X-ray variability of GRS 1915+105 as being due to instabilities of a radiation-pressure dominated disk radiating near the Eddington limit. Finally, several models are constrained which relate observable X-ray properties to the spin of black holes in microquasars. Once further calibrated, these relations may soon turn into a valuable tool to study relativistic effects in strong gravitational fields.Comment: appeared in Nature 414, p. 522 (Nov. 29, 2001

The Hong-Ou-Mandel effect with atoms

Controlling light at the level of individual photons has led to advances in fields ranging from quantum information and precision sensing to fundamental tests of quantum mechanics. A central development that followed the advent of single photon sources was the observation of the Hong-Ou- Mandel (HOM) effect, a novel two-photon path interference phenomenon experienced by indistinguishable photons. The effect is now a central technique in the field of quantum optics, harnessed for a variety of applications such as diagnosing single photon sources and creating probabilistic entanglement in linear quantum computing. Recently, several distinct experiments using atomic sources have realized the requisite control to observe and exploit Hong-Ou-Mandel interference of atoms. This article provides a summary of this phenomenon and discusses some of its implications for atomic systems. Transitioning from the domain of photons to atoms opens new perspectives on fundamental concepts, such as the classification of entanglement of identical particles. It aids in the design of novel probes of quantities such as entanglement entropy by combining well established tools of AMO physics - unity single-atom detection, tunable interactions, and scalability - with the Hong-Ou-Mandel interference. Furthermore, it is now possible for established protocols in the photon community, such as measurement-induced entanglement, to be employed in atomic experiments that possess deterministic single-particle production and detection. Hence, the realization of the HOM effect with atoms represents a productive union of central ideas in quantum control of atoms and photons.Comment: 19 pages, 7 figure

Robust Digital Holography For Ultracold Atom Trapping

We have formulated and experimentally demonstrated an improved algorithm for design of arbitrary two-dimensional holographic traps for ultracold atoms. Our method builds on the best previously available algorithm, MRAF, and improves on it in two ways. First, it allows for creation of holographic atom traps with a well defined background potential. Second, we experimentally show that for creating trapping potentials free of fringing artifacts it is important to go beyond the Fourier approximation in modelling light propagation. To this end, we incorporate full Helmholtz propagation into our calculations.Comment: 7 pages, 4 figure

A 15.65 solar mass black hole in an eclipsing binary in the nearby spiral galaxy Messier 33

Stellar-mass black holes are discovered in X-ray emitting binary systems, where their mass can be determined from the dynamics of their companion stars. Models of stellar evolution have difficulty producing black holes in close binaries with masses >10 solar masses, which is consistent with the fact that the most massive stellar black holes known so all have masses within 1 sigma of 10 solar masses. Here we report a mass of 15.65 +/- 1.45 solar masses for the black hole in the recently discovered system M33 X-7, which is located in the nearby galaxy Messier 33 (M33) and is the only known black hole that is in an eclipsing binary. In order to produce such a massive black hole, the progenitor star must have retained much of its outer envelope until after helium fusion in the core was completed. On the other hand, in order for the black hole to be in its present 3.45 day orbit about its 70.0 +/- 6.9 solar mass companion, there must have been a ``common envelope'' phase of evolution in which a significant amount of mass was lost from the system. We find the common envelope phase could not have occured in M33 X-7 unless the amount of mass lost from the progenitor during its evolution was an order of magnitude less than what is usually assumed in evolutionary models of massive stars.Comment: To appear in Nature October 18, 2007. Four figures (one color figure degraded). Differs slightly from published version. Supplementary Information follows in a separate postin

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

Glucocorticoid sensitivity in Behcet's disease

WOS: 000209773300007PubMed ID: 23781311Objective: Glucocorticoid (GC) sensitivity is highly variable among individuals and has been associated with susceptibility to develop (auto-) inflammatory disorders. The purpose of the study was to assess GC sensitivity in Behcet's disease (BD) by studying the distribution of four GC receptor (GR) gene polymorphisms and by measuring in vitro cellular GC sensitivity. Methods: Healthy controls and patients with BD in three independent cohorts were genotyped for four functional GR gene polymorphisms. To gain insight into functional differences in in vitro GC sensitivity, 19 patients with BD were studied using two bioassays and a whole-cell dexamethasone-binding assay. Finally, mRNA expression levels of GR splice variants (GR-alpha and GR-beta) were measured. Results: Healthy controls and BD patients in the three separate cohorts had similar distributions of the four GR polymorphisms. The Bcll and 9 beta minor alleles frequency differed significantly between Caucasians and Mideast and Turkish individuals. At the functional level, a decreased in vitro cellular GC sensitivity was observed. GR number in peripheral blood mononuclear cells was higher in BD compared with controls. The ratio of GR-alpha/GR-beta mRNA expression levels was significantly lower in BD. Conclusions: Polymorphisms in the GR gene are not associated with susceptibility to BD. However, in vitro cellular GC sensitivity is decreased in BD, possibly mediated by a relative higher expression of the dominant negative GR-b splice variant. This decreased in vitro GC sensitivity might play an as yet unidentified role in the pathophysiology of BD.The Dutch Arthritis AssociationThis work was supported by a grant from The Dutch Arthritis Association

Artificial graphene as a tunable Dirac material

Artificial honeycomb lattices offer a tunable platform to study massless Dirac quasiparticles and their topological and correlated phases. Here we review recent progress in the design and fabrication of such synthetic structures focusing on nanopatterning of two-dimensional electron gases in semiconductors, molecule-by-molecule assembly by scanning probe methods, and optical trapping of ultracold atoms in crystals of light. We also discuss photonic crystals with Dirac cone dispersion and topologically protected edge states. We emphasize how the interplay between single-particle band structure engineering and cooperative effects leads to spectacular manifestations in tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference

X-Ray Emitting Blast Wave from the Recurrent Nova RS Ophiuchi

Stellar explosions such as novae and supernovae produce most of the heavy elements in the Universe. Although the onset of novae from runaway thermonuclear fusion reactions on the surface of a white dwarf in a binary star system is understood[1], the structure, dynamics, and mass of the ejecta are not well known. In rare cases, the white dwarf is embedded in the wind nebula of a red-giant companion; the explosion products plow through the nebula and produce X-ray emission. Early this year, an eruption of the recurrent nova RS Ophiuchi[2,3] provided the first opportunity to perform comprehensive X-ray observations of such an event and diagnose conditions within the ejecta. Here we show that the hard X-ray emission from RS Ophiuchi early in the eruption emanates from behind a blast wave, or outward-moving shock wave, that expanded freely for less than 2 days and then decelerated due to interaction with the nebula. The X-rays faded rapidly, suggesting that the blast wave deviates from the standard spherical shell structure[4-6]. The early onset of deceleration indicates that the ejected shell had a low mass, the white dwarf has a high mass[7], and that RS Ophiuchi is a progenitor of the type of supernova integral to studies of the expansion of the universe.Comment: To appear in Nature; 7 pages, including 2 color figures; removed incorrect statement of embargo polic

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Attitudes and perceptions of Australian pharmacy students towards Complementary and Alternative Medicine – a pilot study

<p>Abstract</p> <p>Background</p> <p>With the increased usage of CAM worldwide comes the demand for its integration into health professional education. However, the incorporation of CAM into health professional curricula is handled quite differently by different institutions and countries. Furthermore, the evaluation of CAM curricula is complicated because students' ability to learn about CAM may be influenced by factors such as student's prior knowledge and motivation, together with the perceptions and attitudes of clinical preceptors.</p> <p>The study aimed to describe the attitudes, perceptions and beliefs of second, third and fourth year pharmacy students towards complementary and alternative medicine (CAM) and to explore factors that might affect attitudes such as learning, preceptors and placements.</p> <p>Methods</p> <p>Pharmacy students from a University in South East Queensland, Australia participated in the study. The study consisted of a cross-sectional survey (n = 110) and semi-structured interviews (n = 9).</p> <p>Results</p> <p>The overall response rate for the survey was 75%, namely 50% (36/72) for second year, 77.3% (34/44) for third year and 97.6% (40/41) for fourth year students. Overall, 95.5% of pharmacy students believe that pharmacists should be able to advise patients about CAM and most (93.7%) have used CAM prior to course enrolment. Students' attitudes to CAM are influenced by the use of CAM by family, friends and self, CAM training, lecturers and to a lesser degree by preceptors. The majority of pharmacy students (89.2%) perceive education about CAM as a core and integral part of their professional degree and favour it over an additional postgraduate degree. However, they see a greater need for education in complementary medicines (such as herbal medicines, vitamins and minerals) than for education in complementary therapies (such as acupuncture, meditation and bio-magnetism). Knowledge and educational input rationalised rather than marginalised students' attitudes towards CAM.</p> <p>Conclusion</p> <p>Pharmacy students perceive education about CAM as a core and integral part of their professional degree. Students' attitudes towards CAM can be influenced by learning, lecturers, preceptors and practice experience. The content and focus of CAM education has to be further investigated and tailored to meet the professional needs of our future health professionals.</p