Single temperature for Monte Carlo optimization on complex landscapes

We propose a new strategy for Monte Carlo (MC) optimization on rugged multidimensional landscapes. The strategy is based on querying the statistical properties of the landscape in order to find the temperature at which the mean first passage time across the current region of the landscape is minimized. Thus, in contrast to other algorithms such as simulated annealing (SA), we explicitly match the temperature schedule to the statistics of landscape irregularities. In cases where this statistics is approximately the same over the entire landscape, or where non-local moves couple distant parts of the landscape, single-temperature MC will outperform any other MC algorithm with the same move set. We also find that in strongly anisotropic Coulomb spin glass and traveling salesman problems, the only relevant statistics (which we use to assign a single MC temperature) is that of irregularities in low-energy funnels. Our results may explain why protein folding in nature is efficient at room temperatures.Comment: 5 pages, 3 figure

Decoherence of a Measure of Entanglement

We demonstrate by an explicit model calculation that the decay of entanglement of two two-state systems (two qubits) is governed by the product of the factors that measure the degree of decoherence of each of the qubits, subject to independent sources of quantum noise. This demonstrates an important physical property that separated open quantum systems can evolve quantum mechanically on time scales larger than the times for which they remain entangled.Comment: 4 pages, 1 figur

High-throughput sequencing reveals a simple model of nucleosome energetics

We use nucleosome maps obtained by high-throughput sequencing to study sequence specificity of intrinsic histone-DNA interactions. In contrast with previous approaches, we employ an analogy between a classical one-dimensional fluid of finite-size particles in an arbitrary external potential and arrays of DNA-bound histone octamers. We derive an analytical solution to infer free energies of nucleosome formation directly from nucleosome occupancies measured in high-throughput experiments. The sequence-specific part of free energies is then captured by fitting them to a sum of energies assigned to individual nucleotide motifs. We have developed hierarchical models of increasing complexity and spatial resolution, establishing that nucleosome occupancies can be explained by systematic differences in mono- and dinucleotide content between nucleosomal and linker DNA sequences, with periodic dinucleotide distributions and longer sequence motifs playing a secondary role. Furthermore, similar sequence signatures are exhibited by control experiments in which genomic DNA is either sonicated or digested with micrococcal nuclease in the absence of nucleosomes, making it possible that current predictions based on high-throughput nucleosome positioning maps are biased by experimental artifacts.Comment: 36 pages, 13 figure

The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis

SummaryOncocytomas are predominantly benign neoplasms possessing pathogenic mitochondrial mutations and accumulation of respiration-defective mitochondria, characteristics of unknown significance. Using exome and transcriptome sequencing, we identified two main subtypes of renal oncocytoma. Type 1 is diploid with CCND1 rearrangements, whereas type 2 is aneuploid with recurrent loss of chromosome 1, X or Y, and/or 14 and 21, which may proceed to more aggressive eosinophilic chromophobe renal cell carcinoma (ChRCC). Oncocytomas activate 5′ adenosine monophosphate-activated protein kinase (AMPK) and Tp53 (p53) and display disruption of Golgi and autophagy/lysosome trafficking, events attributed to defective mitochondrial function. This suggests that the genetic defects in mitochondria activate a metabolic checkpoint, producing autophagy impairment and mitochondrial accumulation that limit tumor progression, revealing a novel tumor-suppressive mechanism for mitochondrial inhibition with metformin. Alleviation of this metabolic checkpoint in type 2 by p53 mutations may allow progression to eosinophilic ChRCC, indicating that they represent higher risk

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Сейсмічний експеримент TTZ-South

The wide-angle reflection and refraction (WARR) TTZ-South transect carried out in 2018 crosses the SW region of Ukraine and the SE region of Poland. The TTZ-South profile targeted the structure of the Earth’s crust and upper mantle of the Trans-European Suture Zone, as well as the southwestern segment of the East European Craton (slope of the Ukrainian Shield). The ~550 km long profile (~230 km in Poland and ~320 km in western Ukraine) is an extension of previously realized projects in Poland, TTZ (1993) and CEL03 (2000). The deep seismic sounding study along the TTZ-South profile using TEXAN and DATA-CUBE seismic stations (320 units) made it possible to obtain high-quality seismic records from eleven shot points (six in Ukraine and five in Poland). This paper presents a smooth P-wave velocity model based on first-arrival travel-time inversion using the FAST (First Arrival Seismic Tomography) code.The obtained image represents a preliminary velocity model which, according to the P-wave velocities, consists of a sedimentary layer and the crystalline crust that could comprise  upper, middle and lower crustal layers. The Moho interface, approximated by the 7.5 km/s isoline, is located at 45—47 km depth in the central part of the profile, shallowing to 40 and 37 km depth in the northern (Radom-Łysogóry Unit, Poland) and southern (Volyno-Podolian Monocline, Ukraine) segments of the profile, respectively. A peculiar feature of the velocity cross-section is a number of high-velocity bodies distinguished in the depth range of 10—35 km. Such high-velocity bodies were detected previously in the crust of the Radom-Łysogóry Unit. These bodies, inferred at depths of 10—35 km, could be allochthonous fragments of what was originally a single mafic body or separate mafic bodies intruded into the crust during the break-up of Rodinia in the Neoproterozoic, which was accompanied by considerable rifting. The manifestations of such magmatism are known in the NE part of the Volyno-Podolian Monocline, where the Vendian trap formation occurs at the surface.Сейсмический профиль TTZ-South с использованием преломленных и отраженных в закритической области преломленных волн, отработанный в 2018 г., пересекает юго-западный район Украины и юго-восточный регион Польши. Профиль TTZ-South был направлен на изучение структуры земной коры и верхней мантии Трансъевропейской шовной зоны (ТЕШЗ) и юго-западного сегмента Восточно-Европейского кратона (склона Украинского щита). Профиль длиной ~550 км (~230 км в Польше и ~320 км на западе Украины) является продолжением ранее реализованных проектов в Польше — профиля TTZ (1993 г.) и CEL03 (2000 г.). Глубинное сейсмическое зондирование по профилю TTZ-South, выполненное с использованием 320 сейсмических станций TEXAN и DATA-CUBE, позволило получить сейсмические записи высокого качества из одиннадцати пунктов взрыва (шесть в Украине и пять в Польше). В данной статье представлена упрощенная Р-скоростная модель, основанная на инверсии времен пробега первых вступлений Р-волн, построенная с использованием программы сейсмической томографии первых вступлений FAST. Полученное изображение представляет собой предварительную скоростную модель, которая состоит из осадочного слоя и кристаллической коры, включающей верхний, средний и нижний ее слои. Поверхность Мохо, аппроксимируемая изолинией 7,5 км/с, расположена на глубине 45—47 км в центральной части профиля, воздымаясь до 40 и 37 км в северной (Радом-Лысогорский блок в Польше) и южной (Волыно-Подольская моноклиналь в Украине) частях профиля соответственно. Особенностью скоростного разреза является ряд высокоскоростных тел, выявленных в диапазоне глубин 10—35 км. Аналогичные высокоскоростные тела ранее были обнаружены в коре Радом-Лысогорского блока. Тела, обнаруженные на глубине 10—35 км, могут быть аллохтонными фрагментами изначально единого массива основных пород или отдельными телами основного состава, внедрившимися в кору в неопротерозое во время раскола суперконтинета Родиния, который сопровождался мощным рифтогенезом. Проявления рифтогенного магматизма известны в северо-восточной части Волыно-Подольской моноклинали, где на поверхность выходят вендские трапы.Сейсмічний профіль TTZ-South з використанням заломлених і відбитих у за критичній зоні заломлених хвиль, відпрацьований у 2018 р., перетинає південно-західний район України і південно-східний регіон Польщі. Профіль TTZ-South був спрямований на вивчення структури земної кори і верхньої мантії Транс'єв ропейської шовної зони (ТЄШЗ) і південно-західного сегмента Східно-Європейського кратона (схила Українського щита). Профіль довжиною ~550 км (~230 км в Польщі і ~320 км на заході України) є продовженням раніше реалізованих проєктів у Польщі — профілю TTZ (1993 р.) і CEL03 (2000 р). Глибинне сейсмічне зондування за профілем TTZ-South, виконане з використанням 320 сейсмічних станцій TEXAN і DATA-CUBE, дало змогу отримати сейсмічні записи високої якості з одинадцяти пунктів вибуху (шість в Україні і п'ять у Польщі). У даній статті представлена спрощена Р-швидкісна модель, що базується на інверсії часів пробігу перших вступів Р-хвиль, побудована з використанням програми сейсмічної томографії перших вступів FAST. Отримане зображення являє собою попередню швидкісну модель, яка складається з осадового шару і кристалічної кори, що включає верхній, середній і нижній її шари. Поверхня Мохо, що апроксимується ізолінією 7,5 км/с, розташована на глибині 45—47 км у центральній частині профілю, здіймається до 40 і 37 км у північній (Радом-Лисогорський блок у Польщі) і південній (Волино-Подільська монокліналь в Україні) частинах профілю відповідно. Особливістю швидкісного розрізу є ряд високошвидкісних тіл, виявлених у діапазоні глибин 10—35 км. Подібні високошвидкісні тіла раніше були виявлені в корі Радом-Лисогірського блоку. Тіла, виявлені на глибині 10—35 км, можуть бути алохтонними фрагментами спочатку єдиного масиву основних порід або окремими тілами основного складу, що впровадилися в кору в неопротерозої під час розколу суперконтінета Родінія, який супроводжувався потужним рифтогенезом. Прояви рифтогенного магматизму відомі в північно-східній частині Волино-Подільської моноклінали, де на поверхню виходять вендські трапи

Crustal and Upper Mantle Velocity Model along the DOBRE-4 Profile from North Dobruja to the Central Region of the Ukrainian Shield : 2. Geotectonic Interpretation

Peer reviewe

Crustal and Upper Mantle Velocity Model along the DOBRE-4 Profile from North Dobruja to the Central Region of the Ukrainian Shield : 1. Seismic Data

For studying the structure of the lithosphere in southern Ukraine, wide-angle seismic studies that recorded the reflected and refracted waves were carried out under the DOBRE-4 project. The field works were conducted in October 2009. Thirteen chemical shot points spaced 35-50 km apart from each other were implemented with a charge weight varying from 600 to 1000 kg. Overall 230 recording stations with an interval of 2.5 km between them were used. The high quality of the obtained data allowed us to model the velocity section along the profile for P-and S-waves. Seismic modeling was carried out by two methods. Initially, trial-and-error ray tracing using the arrival times of the main reflected and refracted P-and S-phases was conducted. Next, the amplitudes of the recorded phases were analyzed by the finite-difference full waveform method. The resulting velocity model demonstrates a fairly homogeneous structure from the middle to lower crust both in the vertical and horizontal directions. A drastically different situation is observed in the upper crust, where the Vp velocities decrease upwards along the section from 6.35 km/s at a depth of 15-20 km to 5.9-5.8 km/s on the surface of the crystalline basement; in the Neoproterozoic and Paleozoic deposits, it diminishes from 5.15 to 3.80 km/s, and in the Mesozoic layers, it decreases from 2.70 to 2.30 km/s. The sub-crustal Vp gradually increases downwards from 6.50 to 6.7-6.8 km/s at the crustal base, which complicates the problem of separating the middle and lower crust. The Vp velocities above 6.80 km/s have not been revealed even in the lowermost part of the crust, in contrast to the similar profiles in the East European Platform. The Moho is clearly delineated by the velocity contrast of 1.3-1.7 km/s. The alternating pattern of the changes in the Moho depths corresponding to Moho undulations with a wavelength of about 150 km and the amplitude reaching 8 to 17 km is a peculiarity of the velocity model.Peer reviewe

Lithospheric structure along wide-angle seismic profile GEORIFT 2013 in Pripyat–Dnieper–Donets Basin (Belarus and Ukraine)

The GEORIFT 2013 (GR'13) WARR (wide-angle reflection and refraction) experiment was carried out in 2013 in the territory of Belarus and Ukraine with broad international co-operation. The aim of the work is to study basin architecture and deep structure of the Pripyat-Dnieper-Donets Basin (PDDB), which is the deepest and best studied Palaeozoic rift basin in Europe. The PDDB is located in the southern part of the East European Craton (EEC) and crosses Sarmatia-one of the three segments of the EEC. The PDDB was formed by Late Devonian rifting associated with domal basement uplift and magmatism. The GR'13 extends in NW SE direction along the PDDB strike and crosses the Pripyat Trough (PT) and Dnieper Graben (DG) separated by the Bragin Uplift (BU) of the basement. The field acquisition along the GR'13 (of 670 km total length) involved 14 shots and recorders deployed every similar to 2.2 km for several shot points. The good quality of the data, with first arrivals visible up to 670 km for several shot points, allowed for construction of a velocity model extending to 80 km depth using ray-tracing modelling. The thickness of the sediments (Vp <6.0 km s(-1)) varies from 1-4 km in the PT, to 5 km in the NW part of the DG, to 10-13 km in the SE part of the profile. Below the DG, at similar to 330-530 km distance, we observed an upwarping of the lower crust (with Vp of similar to 7.1 km s(-1)) to 25 km depth that represents a rift pillow or mantle underplate. The Moho shallows southeastwards from similar to 47 km in the PT to 40-38 km in the DG with mantle velocities of 8.35 and similar to 8.25 km s(-1) in the PT and DG, respectively. A near-horizontal mantle discontinuity was found beneath BU (a transition zone from the PT to the DG) at the depth of 50-47 km. It dips to the depth of similar to 60 km at distances of 360-405 km, similar to the intersecting EUROBRIDGE'97 profile. The crust and upper mantle structure on the GR'13 may reflect varying intensity of rifting in the PDDB from a passive stage in the PT to active rifting in the DG. The absence of Moho uplift and relatively thick crystalline crust under the PT is explained by its tectonic position as a closing unit of the PDDB, with a gradual attenuation of rifting from the southeast to the northwest. The most active stage of rifting is evidenced in the DG by a shallower Moho and by a presence of a rift pillow caused by mafic and ultramafic intrusions during the active phase. The junction of the PT and the DG (the BU) locates just at its intersection with the NS regional tectonic zone Odessa-Gomel. Most likely, the 'blocking' effect of this zone did not allow for further propagation of active rifting to the NW.Peer reviewe

Quantitative Treatment of Decoherence

We outline different approaches to define and quantify decoherence. We argue that a measure based on a properly defined norm of deviation of the density matrix is appropriate for quantifying decoherence in quantum registers. For a semiconductor double quantum dot qubit, evaluation of this measure is reviewed. For a general class of decoherence processes, including those occurring in semiconductor qubits, we argue that this measure is additive: It scales linearly with the number of qubits.Comment: Revised version, 26 pages, in LaTeX, 3 EPS figure