The Authenticity of the James Ossuary

An archaeometric analysis of the James Ossuary inscription “James Son of Joseph Brother of Jesus” strengthens the contention that the ossuary and its engravings are authentic. The beige patina can be observed on the surface of the ossuary, continuing gradationally into the engraved inscription. Fine long striations made by the friction of falling roof rocks continuously crosscut the letters. Many dissolution pits are superimposed on several of the letters of the inscription. In addition to calcite and quartz, the patina contains the following minerals: apatite, whewellite and weddelite (calcium oxalate). These minerals result from the biogenic activity of microorganisms that require a long period of time to form a bio-patina. Moreover, the heterogeneous existence of wind-blown microfossils (nannofossils and foraminifers) and quartz within the patina of the ossuary, including the lettering zone, reinforces the authenticity of the inscription

Building Stones from a Quarry in Northern Jerusalem Probably Used in the Temple Mount: 5 Years After the Discovery

During the summer of 2009 a quarry was unearthed in the Ramat Shlomo neighborhood, northern Jerusalem, during land development for the construction of a new school. The excavated area of the quarry was about one acre and is indicative of substantial mining activity in the Turonian (Bina Formation) white limestone beds (known locally as “meleke” = king) from which blocks up to 8 meters in length and 1-2 meters in width were excavated. The dimensions of the large blocks are very rare in known domestic ancient quarries, and thus were considered to be relocated for use in the construction of the walls of the Temple Mount. The distance from the quarry (eastward) to the main North-South old (Nablus-Jerusalem) road is around 600 m at the same topographical level (~795 m asl). Along the main road it is about 3 km further south to the Temple Mount, located around 50-70 m lower. The heavy blocks were probably carried by carts driven by oxen, sloping down to the huge Herodian construction project. Today most of the unearthed site is a school but a small part of the excavated old quarry was preserved in the eastern yard of that new complex. Recent examination reveals that the original quarry was probably much larger than the excavated site. The uninhabited and overgrown area between Ramat Shlomo and Shuafat has numerous remnants of quarried walls. Preliminary field evidence and aerial photos indicate a contiguous quarrying area some 350 m long along strike (SSW-NNE) and about 150 m wide. Thus it appears that the ancient area that was quarried was about 50,000 m2. Since the original dimensions of the quarry are uncertain it is, at this time, difficult to estimate the amount of stone that was actually mined. However, it is probable that this area was an important source of high quality building stone for the construction of the Second Temple

Complementarity and Scientific Rationality

Bohr's interpretation of quantum mechanics has been criticized as incoherent and opportunistic, and based on doubtful philosophical premises. If so Bohr's influence, in the pre-war period of 1927-1939, is the harder to explain, and the acceptance of his approach to quantum mechanics over de Broglie's had no reasonable foundation. But Bohr's interpretation changed little from the time of its first appearance, and stood independent of any philosophical presuppositions. The principle of complementarity is itself best read as a conjecture of unusually wide scope, on the nature and future course of explanations in the sciences (and not only the physical sciences). If it must be judged a failure today, it is not because of any internal inconsistency.Comment: 29 page

Cross-talk and interference enhance information capacity of a signaling pathway

A recurring motif in gene regulatory networks is transcription factors (TFs) that regulate each other, and then bind to overlapping sites on DNA, where they interact and synergistically control transcription of a target gene. Here, we suggest that this motif maximizes information flow in a noisy network. Gene expression is an inherently noisy process due to thermal fluctuations and the small number of molecules involved. A consequence of multiple TFs interacting at overlapping binding-sites is that their binding noise becomes correlated. Using concepts from information theory, we show that in general a signaling pathway transmits more information if 1) noise of one input is correlated with that of the other, 2) input signals are not chosen independently. In the case of TFs, the latter criterion hints at up-stream cross-regulation. We demonstrate these ideas for competing TFs and feed-forward gene regulatory modules, and discuss generalizations to other signaling pathways. Our results challenge the conventional approach of treating biological noise as uncorrelated fluctuations, and present a systematic method for understanding TF cross-regulation networks either from direct measurements of binding noise, or bioinformatic analysis of overlapping binding-sites.Comment: 28 pages, 5 figure

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

BACKGROUND: The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. METHODS: Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. RESULTS: Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). CONCLUSIONS: iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials

Elastic lever arm model for myosin V

We present a mechanochemical model for myosin V, a two-headed processive motor protein. We derive the properties of a dimer from those of an individual head, which we model both with a 4-state cycle (detached, attached with ADP.Pi, attached with ADP and attached without nucleotide) and alternatively with a 5-state cycle (where the power stroke is not tightly coupled to the phosphate release). In each state the lever arm leaves the head at a different, but fixed, angle. The lever arm itself is described as an elastic rod. The chemical cycles of both heads are coordinated exclusively by the mechanical connection between the two lever arms. The model explains head coordination by showing that the lead head only binds to actin after the power stroke in the trail head and that it only undergoes its power stroke after the trail head unbinds from actin. Both models (4- and 5-state) reproduce the observed hand-over-hand motion and fit the measured force-velocity relations. The main difference between the two models concerns the load dependence of the run length, which is much weaker in the 5-state model. We show how systematic processivity measurement under varying conditions could be used to distinguish between both models and to determine the kinetic parameters.Comment: 15 pages, 15 figures, to appear in Biophys.

Kinesin Is an Evolutionarily Fine-Tuned Molecular Ratchet-and-Pawl Device of Decisively Locked Direction

Conventional kinesin is a dimeric motor protein that transports membranous organelles toward the plus-end of microtubules (MTs). Individual kinesin dimers show steadfast directionality and hundreds of consecutive steps, yetthe detailed physical mechanism remains unclear. Here we compute free energies for the entire dimer-MT system for all possible interacting configurations by taking full account of molecular details. Employing merely first principles and several measured binding and barrier energies, the system-level analysis reveals insurmountable energy gaps between configurations, asymmetric ground state caused by mechanically lifted configurational degeneracy, and forbidden transitions ensuring coordination between both motor domains for alternating catalysis. This wealth of physical effects converts a kinesin dimer into a molecular ratchet-and-pawl device, which determinedly locks the dimer's movement into the MT plus-end and ensures consecutive steps in hand-over-hand gait.Under a certain range of extreme loads, however, the ratchet-and-pawl device becomes defective but not entirely abolished to allow consecutive back-steps. This study yielded quantitative evidence that kinesin's multiple molecular properties have been evolutionarily adapted to fine-tune the ratchet-and-pawl device so as to ensure the motor's distinguished performance.Comment: 10 printed page

‘“For Without Vanity I’m Better Known”: Restoration Actors and Metatheatre on the London Stage.’

Published version of article deposited in accordance with SHERPA Romeo guidelines. © Cambridge University Press, 2011

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint

Qual a Contribuiçao do Tilt Training (treinamento postural) na Prevençao da Síncope Vasovagal?

Histórico: A síncope vasovagal é um dos quadros clínicos mais comuns em adultos jovens. Estudos anteriores demonstram a eficiência do tilt training (treinamento postural) no tratamento desse transtorno clínico. Realizou-se um estudo prospectivo e randomizado com o objetivo de avaliar a contribuiçao do tilt training no tratamento de adultos jovens acometidos pela síncope vasovagal. Métodos: Quarenta e seis soldados, 25 dos quais do sexo masculino, média de idade de 19,4 ± 0,8 anos e diagnóstico clínico de síncope vasovagal pelo tilt test, foram divididos aleatoriamente em dois grupos: um grupo controle e outro submetido a tilt training diariamente, por três meses. Nos dois grupos, os participantes foram instruídos a aumentar a ingestao de líquidos e sal e evitar situaçoes indutoras da síncope, tais como permanecer em pé por períodos longos. Resultados: A adesao ao programa de treinamento, caracterizada pela realizaçao de 50% ou mais das sessoes diárias de tilt training, foi de 91% durante o primeiro mês, caindo para 58% nos três meses. Os que realizaram o treinamento apresentaram uma média (distância interquartílica) de 5,0 episódios de síncope (0,5 a 16,0) durante um ano de acompanhamento, enquanto o grupo controle apresentou média de 2,0 episódios (0 a 6,0; P = 0,737). Após a randomizaçao, nao houve diferença significativa no tempo de ocorrência do primeiro episódio de síncope entre os dois grupos: média de 1,0 por mês (0,5 a 2,0) no grupo em tratamento e 0,8 (0,5 a 2,0) no grupo controle (P = 0,336). Conclusoes: A realizaçao diária do tilt training, aliada às modificaçoes de estilo de vida, nao produziu melhora no resultado do tratamento de adultos jovens com síncope vasovagal. Verificou-se ainda a dificuldade de obter boa adesao ao programa de treinamento postural