Finding Dominators via Disjoint Set Union

The problem of finding dominators in a directed graph has many important applications, notably in global optimization of computer code. Although linear and near-linear-time algorithms exist, they use sophisticated data structures. We develop an algorithm for finding dominators that uses only a "static tree" disjoint set data structure in addition to simple lists and maps. The algorithm runs in near-linear or linear time, depending on the implementation of the disjoint set data structure. We give several versions of the algorithm, including one that computes loop nesting information (needed in many kinds of global code optimization) and that can be made self-certifying, so that the correctness of the computed dominators is very easy to verify

Observations on parental care in the glass frog Hyalinobatrachium orientale (Anura: Centrolenidae) from Tobago, with comments on its natural history

We made observations on parental care in the glass frog Hyalinobatrachium orientale (Anura: Centrolenidae) from Tobago, and comments on its natural histor

Synthesis and evaluation of novel 2,4-disubstituted arylthiazoles against T. brucei.

The design, synthesis and pharmacological evaluation of the 4-substituted-2-[3-(adamant-1-yl)-4-fluorophenyl]thiazoles 1a-j, the 4-substituted-2-[4-(adamant-1-yl)phenyl]thiazoles 2a-h, the 2-substituted-4-[4-(adamant-1-yl)phenyl]thiazoles 3a-e, the N-substituted 2-phenylthiazol-4-ethylamides 4a, b and the N-substituted 4-phenylthiazol-2-ethylamides 4c, d is described. Compounds 1a and 2a exhibit trypanocidal activity in the range of IC50 = 0.42 μM and IC50 = 0.80 μM, respectively. Both of these derivatives bear a lipophilic end, which consists of a 4-(1-adamantyl) phenyl or a 3-(1-adamantyl)phenyl moiety, a 1,3-thiazole ring and a functional end, which comprises of an alkylamine and can be considered as promising candidates for the treatment of Trypanosoma brucei infections

Hachimoji DNA and RNA: A genetic system with eight building blocks

Reported here are DNA and RNA-like systems built from eight (hachi-) nucleotide letters (-moji) that form four orthogonal pairs. This synthetic genetic biopolymer meets the structural requirements needed to support Darwinism, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to double the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos

Cytogenetic and molecular analyses of de novo translocation dic(9;13)(p11.2;p12) in an infertile male

BACKGROUND: Whole arm t(9;13)(p11;p12) translocations are rare and have been described only a few times; all of the previously reported cases were familial. RESULTS: We present here an infertile male carrier with a whole-arm reciprocal translocation dic(9;13)(p11.2;p12) revealed by GTG-, C-, and NOR-banding karyotypes with no mature sperm cells in his ejaculate. FISH and genome-wide 400 K CGH microarray (Agilent) analyses demonstrated a balanced chromosome complement and further characterised the abnormality as a dicentric chromosome (9;13): dic(9;13)(pter→p11.2::p12→qter),neo(9)(pter→p12→neo→p11.2). An analysis of the patient’s ejaculated cells identified immature germ cells at different phases of spermatogenesis but no mature spermatozoa. Most (82.5%) of the germ cells were recognised as spermatocytes at stage I, and the cell nuclei were most frequently found in pachytene I (41.8%). We have also undertaken FISH analysis and documented an increased rate of aneuploidy of chromosomes 15, 18, X and Y in the peripheral blood leukocytes of our patient. To study the aneuploidy risk in leukocytes, we have additionally included 9 patients with non-obstructive azoospermia with normal karyotypes. CONCLUSIONS: We propose that the azoospermia observed in the patient with the dic(9;13)(p11.2;p12) translocation was most likely a consequence of a very high proportion (90%) of association between XY bivalents and quadrivalent formations in prophase I

Synthesis of diphenoxyadamantane alkylamines with pharmacological interest.

In this work, the synthesis and the pharmacological evaluation of diphenoxyadamantane alkylamines Ia-f and IIa-f is described. The new diphenoxy-substituted adamantanes share structural features present in trypanocidal and antitubercular agents. 1-Methylpiperazine derivative Ia is the most potent against T. brucei compound, whilst its hexylamine congener IIf exhibits a significant antimycobacterial activity

AFM imaging and nanoindentation of polymer of intrinsic microporosity PIM-1

Polymers of intrinsic microporosity (PIMs) have promising gas adsorption properties for potential applications such as incorporation into high-pressure hydrogen storage tanks in an effort to increase the storage capacity or decrease the operating pressure. Such applications require detailed mechanical characterisation and determination of the structure-properties relationships to enable optimisation of the interface between the polymer and the tank. In this study, we show that Atomic Force Microscopy (AFM) nanoindentation can be used to determine the elastic modulus of cast PIM-1 films and that this property is depth-dependent. Average values of elastic modulus obtained experimentally were 1.87 GPa and are compared with elastic tensile modulus and storage tensile modulus obtained in previous studies. In addition, Scanning Electron Microscopy (SEM) and AFM imaging was performed to investigate the surface structure of the cast PIM-1 film, which has been shown to be highly granular

Fragment- and structure-based drug discovery for developing therapeutic agents targeting the DNA Damage Response

Cancer will directly affect the lives of over one-third of the population. The DNA Damage Response (DDR) is an intricate system involving damage recognition, cell cycle regulation, DNA repair, and ultimately cell fate determination, playing a central role in cancer etiology and therapy. Two primary therapeutic approaches involving DDR targeting include: combinatorial treatments employing anticancer genotoxic agents; and synthetic lethality, exploiting a sporadic DDR defect as a mechanism for cancer-specific therapy. Whereas, many DDR proteins have proven “undruggable”, Fragment- and Structure-Based Drug Discovery (FBDD, SBDD) have advanced therapeutic agent identification and development. FBDD has led to 4 (with ∼50 more drugs under preclinical and clinical development), while SBDD is estimated to have contributed to the development of >200, FDA-approved medicines. Protein X-ray crystallography-based fragment library screening, especially for elusive or “undruggable” targets, allows for simultaneous generation of hits plus details of protein-ligand interactions and binding sites (orthosteric or allosteric) that inform chemical tractability, downstream biology, and intellectual property. Using a novel high-throughput crystallography-based fragment library screening platform, we screened five diverse proteins, yielding hit rates of ∼2–8% and crystal structures from ∼1.8 to 3.2 Å. We consider current FBDD/SBDD methods and some exemplary results of efforts to design inhibitors against the DDR nucleases meiotic recombination 11 (MRE11, a.k.a., MRE11A), apurinic/apyrimidinic endonuclease 1 (APE1, a.k.a., APEX1), and flap endonuclease 1 (FEN1)

Residual trapping of supercritical CO2 in oil-wet sandstone

Residual trapping, a key CO2 geo-storage mechanism during the first decades of a sequestration project, immobilizes micrometre sized CO2 bubbles in the pore network of the rock. This mechanism has been proven to work in clean sandstones and carbonates; however, this mechanism has not been proven for the economically most important storage sites into which CO2 will be initially injected at industrial scale, namely oil reservoirs. The key difference is that oil reservoirs are typically oil-wet or intermediate-wet, and it is clear that associated pore-scale capillary forces are different. And this difference in capillary forces clearly reduces the capillary trapping capacity (residual trapping) as we demonstrate here. For an oil-wet rock (water contact angle θ = 130°) residual CO2 saturation SCO2,r (≈8%) was approximately halved when compared to a strongly water-wet rock (θ = 0°; SCO2,r ≈ 15%). Consequently, residual trapping is less efficient in oil-wet reservoirs

CO2 wettability of caprocks: Implications for structural storage capacity and containment security

© 2015. American Geophysical Union. All Rights Reserved. Structural trapping, the most important CO2 geostorage mechanism during the first decades of a sequestration project, hinges on the traditional assumption that the caprock is strongly water wet. However, this assumption has not yet been verified; and it is indeed not generally true as we demonstrate here. Instead, caprock can be weakly water wet or intermediate wet at typical storage conditions; and water wettability decreases with increasing pressure or temperature. Consequently, a lower storage capacity can be inferred for structural trapping in such cases