Discovering Love numbers through resonance excitation during extreme mass ratio inspirals

General Relativity predicts that black holes do not possess an internal structure and consequently cannot be excited. This leads to a specific prediction about the waveform of gravitational waves, which they emit during a binary black hole inspiral and to the vanishing of their Love numbers. However, if astrophysical black holes do possess an internal structure, their Love numbers would no longer vanish, and they could be excited during an inspiral by the transfer of orbital energy. This would affect the orbital period and lead to an observable imprint on the emitted gravitational waves waveform. The effect is enhanced if one of the binary companions is resonantly excited. We discuss the conditions for resonant excitation of a hypothetical internal structure of black holes and calculate the phase change of the gravitational waves waveform that is induced due to such resonant excitation during intermediate- and extreme-mass-ratio inspirals. We then relate the phase change to the electric quadrupolar Love number of the larger companion, which is resonantly excited by its smaller companion. We discuss the statistical error on measuring the Love number by LISA and show that, because of this phase change, the statistical error is small even for small values of the Love number. Our results provide a strong indication that the Love number could be detected by LISA with remarkable accuracy, much higher than what can be achieved via tidal deformation effects. Our results further indicate that resonant excitation of the central black hole during an extreme- or intermediate-mass-ratio inspirals is the most promising effect for putting bounds on, or detecting, non-vanishing tidal Love numbers of black holes.Comment: 23 pages, 2 figure

Fermi-bubble bulk and edge analysis reveals dust, cooling breaks, and cosmic-ray diffusion, facilitating a self-consistent model

The full, radio to $\gamma$-ray spectrum of the Fermi bubbles is shown to be consistent with standard strong-shock electron acceleration at the bubble edge, without ad-hoc energy cutoffs, if the ambient interstellar radiation is strong; the $\gamma$-ray cooling break should then have a microwave counterpart, undetected until now. Indeed, a broadband bubble-edge analysis uncovers a pronounced downstream dust component, which masked the anticipated $\sim35$ GHz spectral break, and the same overall radio softening consistent with Kraichnan diffusion previously reported in $\gamma$-rays.Comment: 6 pages, 3 figures, SI; comments welcom

Regulation of Gonadotropin-Releasing Hormone (GnRH)-Receptor Gene Expression in Tilapia: Effect of GnRH and Dopamine

The present work was designed to study certain aspects of the endocrine regulation of gonadotropin-releasing hormone receptor (GnRH-R) in the pituitary of the teleost fish tilapia. A GnRH-R was cloned from the pituitary of hybrid tilapia (taGnRH-R) and was identified as a typical seven-transmembrane receptor. Northern blot analysis revealed a single GnRH-R transcript in the pituitary of approximately 2.3 kilobases. The taGnRH-R mRNA levels were significantly higher in females than in males. Injection of the salmon GnRH analog (sGnRHa; 5–50 μg/kg) increased the steady-state levels of taGnRH-R mRNA, with the highest response recorded at 25 μg/kg and at 36 h. At the higher dose of sGnRHa (50 μg/kg), taGnRH-R transcript appeared to be down-regulated. Exposure of tilapia pituitary cells in culture to graded doses (0.1–100 nM) of seabream (sbGnRH = GnRH I), chicken II (cGnRH II), or salmon GnRH (sGnRH = GnRH III) resulted in a significant increase in taGnRH-R mRNA levels. The highest levels of both LH release and taGnRH-R mRNA levels were recorded after exposure to cGnRH II and the lowest after exposure to sbGnRH. The dopamine-agonist quinpirole suppressed LH release and mRNA levels of taGnRH-R, indicating an inhibitory effect on GnRH-R synthesis. Collectively, these data provide evidence that GnRH in tilapia can up- regulate, whereas dopamine down-regulates, taGnRH-R mRNA levels

The Natural History and Predictors for Intervention in Patients with Small Renal Mass Undergoing Active Surveillance

Aim. To describe the natural history of small renal mass on active surveillance and identify parameters that could help in predicting the need for intervention in patients with small renal masses undergoing active surveillance. We also discuss the need for renal biopsy in the management of these patients. Methods. A retrospective analysis of 78 renal masses ≤4 cm diagnosed at our Urology Department at Bnai Zion Medical Center between September 2003 and March 2012. Results. Seventy patients with 78 small renal masses were analyzed. The mean age at diagnosis was 68 years (47–89). The mean follow-up period was 34 months (12–112). In 54 of 78 masses there was a growth of at least 2 mm between imaging on last available follow-up and diagnosis. Eight of the 54 (15%) masses which grew in size underwent a nephron-sparing surgery, of which two were oncocytomas and six were renal cell carcinoma. Growth rate and mass diameter on diagnosis were significantly greater in the group of patients who underwent a surgery. Conclusions. Small renal masses might eventually be managed by active surveillance without compromising survival or surgical approach. All masses that were eventually excised underwent a nephron-sparing surgery. None of the patients developed metastases

Discovering Love numbers through resonance excitation during extreme mass ratio inspirals

General Relativity predicts that black holes do not possess an internalstructure and consequently cannot be excited. This leads to a specificprediction about the waveform of gravitational waves, which they emit during abinary black hole inspiral and to the vanishing of their Love numbers. However,if astrophysical black holes do possess an internal structure, their Lovenumbers would no longer vanish, and they could be excited during an inspiral bythe transfer of orbital energy. This would affect the orbital period and leadto an observable imprint on the emitted gravitational waves waveform. Theeffect is enhanced if one of the binary companions is resonantly excited. Wediscuss the conditions for resonant excitation of a hypothetical internalstructure of black holes and calculate the phase change of the gravitationalwaves waveform that is induced due to such resonant excitation duringintermediate- and extreme-mass-ratio inspirals. We then relate the phase changeto the electric quadrupolar Love number of the larger companion, which isresonantly excited by its smaller companion. We discuss the statistical erroron measuring the Love number by LISA and show that, because of this phasechange, the statistical error is small even for small values of the Lovenumber. Our results provide a strong indication that the Love number could bedetected by LISA with remarkable accuracy, much higher than what can beachieved via tidal deformation effects. Our results further indicate thatresonant excitation of the central black hole during an extreme- orintermediate-mass-ratio inspirals is the most promising effect for puttingbounds on, or detecting, non-vanishing tidal Love numbers of black holes.<br

Bone Involvement in Hyperphosphatemic Familial Tumoral Calcinosis: A New Phenotypic Presentation

Mutations in FGF23, KL, and GALNT3 have been identified as the cause for the development of hyperphosphatemic familial tumoral calcinosis (HFTC). Patients with HFTC typically present in childhood or adolescence with periarticular soft tissue deposits that eventually progress to disrupt normal joint articulation. Mutations in the GALNT3 gene were shown to account for the hyperphosphatemic state in both HFTC and hyperostosis-hyperphosphatemia syndrome (HHS), the latter characterized by bone involvement. We present the case of a patient of a Druze ethnic origin with known HFTC that presented to our department with the first documented case of pathologic fracture occurring secondary to the disease. Our report introduces this new phenotypic presentation, suggests a potential role for prophylactic bone screening, and highlights the need for preconception genetic screening in selected populations

CSI-OMIM - Clinical Synopsis Search in OMIM

<p>Abstract</p> <p>Background</p> <p>The OMIM database is a tool used daily by geneticists. Syndrome pages include a Clinical Synopsis section containing a list of known phenotypes comprising a clinical syndrome. The phenotypes are in free text and different phrases are often used to describe the same phenotype, the differences originating in spelling variations or typing errors, varying sentence structures and terminological variants.</p> <p>These variations hinder searching for syndromes or using the large amount of phenotypic information for research purposes. In addition, negation forms also create false positives when searching the textual description of phenotypes and induce noise in text mining applications.</p> <p>Description</p> <p>Our method allows efficient and complete search of OMIM phenotypes as well as improved data-mining of the OMIM phenome. Applying natural language processing, each phrase is tagged with additional semantic information using UMLS and MESH. Using a grammar based method, annotated phrases are clustered into groups denoting similar phenotypes. These groups of synonymous expressions enable precise search, as query terms can be matched with the many variations that appear in OMIM, while avoiding over-matching expressions that include the query term in a negative context. On the basis of these clusters, we computed pair-wise similarity among syndromes in OMIM. Using this new similarity measure, we identified 79,770 new connections between syndromes, an average of 16 new connections per syndrome. Our project is Web-based and available at <url>http://fohs.bgu.ac.il/s2g/csiomim</url></p> <p>Conclusions</p> <p>The resulting enhanced search functionality provides clinicians with an efficient tool for diagnosis. This search application is also used for finding similar syndromes for the candidate gene prioritization tool S2G.</p> <p>The enhanced OMIM database we produced can be further used for bioinformatics purposes such as linking phenotypes and genes based on syndrome similarities and the known genes in Morbidmap.</p

Rapid clearance of cellular debris by microglia limits secondary neuronal cell death after brain injury in vivo

Moderate or severe traumatic brain injury (TBI) causes widespread neuronal cell death. Microglia, the resident macrophages of the brain, react to injury by migrating to the lesion site, where they phagocytose cellular debris. Microglial phagocytosis can have both beneficial (e.g. debris clearance) and detrimental (e.g. respiratory burst, phagoptosis) consequences. Hence, whether the overall effect of microglial phagocytosis after brain injury in vivo is neuroprotective or neurotoxic is not known. Here, we establish a system with which to carry out dynamic real-time analyses of the mechanisms regulating cell death after brain injury in vivo. We show that mechanical injury to the larval zebrafish brain induces distinct phases of primary and secondary cell death. Excitotoxicity contributes to secondary cell death in zebrafish, reflecting findings from mammals. Microglia arrive at the lesion site within minutes of injury, where they rapidly engulf dead cells. Importantly, the rate of secondary cell death is increased when the rapid removal of cellular debris by microglia is reduced pharmacologically or genetically. In summary, our results provide evidence that microglial debris clearance is neuroprotective after brain injury in vivo

A Mild Form of SLC29A3 Disorder: A Frameshift Deletion Leads to the Paradoxical Translation of an Otherwise Noncoding mRNA Splice Variant

We investigated two siblings with granulomatous histiocytosis prominent in the nasal area, mimicking rhinoscleroma and Rosai-Dorfman syndrome. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous frameshift deletion in SLC29A3, which encodes human equilibrative nucleoside transporter-3 (hENT3). Germline mutations in SLC29A3 have been reported in rare patients with a wide range of overlapping clinical features and inherited disorders including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, and Faisalabad histiocytosis. With the exception of insulin-dependent diabetes and mild finger and toe contractures in one sibling, the two patients with nasal granulomatous histiocytosis studied here displayed none of the many SLC29A3-associated phenotypes. This mild clinical phenotype probably results from a remarkable genetic mechanism. The SLC29A3 frameshift deletion prevents the expression of the normally coding transcripts. It instead leads to the translation, expression, and function of an otherwise noncoding, out-of-frame mRNA splice variant lacking exon 3 that is eliminated by nonsense-mediated mRNA decay (NMD) in healthy individuals. The mutated isoform differs from the wild-type hENT3 by the modification of 20 residues in exon 2 and the removal of another 28 amino acids in exon 3, which include the second transmembrane domain. As a result, this new isoform displays some functional activity. This mechanism probably accounts for the narrow and mild clinical phenotype of the patients. This study highlights the ‘rescue’ role played by a normally noncoding mRNA splice variant of SLC29A3, uncovering a new mechanism by which frameshift mutations can be hypomorphic