Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors.

BACKGROUND BAY 43--9006, an oral multi-kinase inhibitor, targets serine-threonine kinases and receptor tyrosine kinases, and affects the tumor and vasculature in preclinical models. Based on its pharmacologic effect, it may be a useful cancer treatment. This study determined the maximum tolerated dose (MTD) of BAY 43-9006 in 42 patients with advanced, refractory metastatic or recurrent solid tumors. Dose-limiting toxicities (DLTs), safety, pharmacokinetics and tumor response were also evaluated. PATIENTS AND METHODS In this open-label, phase I, dose-escalation study, BAY 43--9,006 was administered orally in repeated cycles of 35 days (28 days on/7 days off). Eight doses were investigated: from 50 mg every fourth day to 600 mg twice daily. Treatment continued until unacceptable toxicity, tumor progression or death. RESULTS The MTD was 400 mg twice daily. BAY 43-9006 was well tolerated, with mild to moderate toxicities; only six patients discontinued study therapy due to adverse events. DLTs consisted of hand-foot skin reaction in three of seven patients receiving 600 mg twice daily. Stable disease was achieved in 22% of patients; median duration of stable disease was 7.2 months. Consistent with its observed half-life of approximately 27 h, BAY 43-9, 006 accumulated on multiple dosing. Increases in exposure were less than proportional to the increases in dose. CONCLUSIONS Results indicate that further clinical investigation of BAY 43--9006 is warranted, and suggest it could be a promising future therapy for patients with cancer.
Phylogenetics of Ogyges Kaup and the biogeography of Nuclear Central America (Coleoptera, Passalidae)

Abstract A phylogenetic morphological analysis of the genus Ogyges Kaup, distributed in Nuclear Central America, from Chiapas, Mexico, to northwestern Nicaragua was undertaken. Five species of Proculejus Kaup, distributed north of the Isthmus of Tehuantepec in Mexico, were selected as outgroup. Ogyges was recovered as monophyletic with three species groups: championi, laevissimus, and crassulus. Each species group shows a distinct, generally allopatric distribution. The O. championi species group, with ten species, is distributed in the Maya block, more specifically in the mountainous system north of the Motozintla-Comaltitlán fault in Chiapas, and north of the dry valleys of the Cuilco and Motagua rivers in Guatemala. The two remaining species groups are distributed in the Chortis block. The O. laevissimus species group, including seven species, ranges mostly along the Pacific Volcanic Chain from Guatemala to El Salvador, and from southeastern Honduras to the northwestern area of Nicaragua. The O. crassulus species group, with ten species, is distributed from northeastern Guatemala (Merendón) to northern Honduras. The Isthmus of Tehuantepec in Mexico, the Motagua-Cuilco and Motozintla-Comaltitlán sutures zones in Chiapas and Guatemala, the lowland valleys of Colón and Comalí rivers between Nicaragua and Honduras (or, perhaps, the northern suture of the Siuna Terrane in Nicaragua), the Guayape fault system in Honduras, and the intricate dry valleys of Ulúa-Chamelecón-Olancho in Honduras, are hypothesized to have acted as barriers that affected the geographical distribution of Ogyges, as well as probably other montane organisms.
The Meaning of “Natural”

The meaning of the desirable attribute “natural” was explored in two samples, American college students and adults in the Philadelphia jury pool. Participants rated the naturalness of a variety of “natural” entities, before and after they were transformed by operations such as freezing, adding or removing components, mixing with other natural or unnatural entities, domestication, and genetic engineering. Results support four hypotheses. First, the principle of contagion accounts for many aspects of the reduction of naturalness by contact with unnatural entities. Second, chemical transformations reduce naturalness much more than physical transformations do. Third, the history of an entity's processing is more important in determining its naturalness than is the nature of the entity's contents. Fourth, mixing like natural entities (e.g., water from different sources) does not markedly reduce naturalness. The insertion of a gene from another species, the process used in producing genetically modified organisms, produces the biggest drop in naturalness; domestication, a human-accomplished activity that changes genotype and phenotype in major ways, is considered much less damaging to naturalness.
A STUDY OF THE EFFECTS OF DEXCLAMOL AS THE NEUROLEPTIC COMPONENT IN NEUROLEPTANAESTHESIA

In a double-blind cross-over study in dogs, dexclamol was compared with droperidol as the neuro-leptic component of a neuroleptanalgesic combination. Fentanyl was the narcotic analgesic. Neuro-leptanaesthesia was induced with a mixture of the neuroleptic, the analgesic and nitrous oxide in oxygen. Dexclamol 200 ng/kg i.v. was as effective as droperidol at the same dose in inducing neuro-lepsy and in supplementing nitrous oxide anaesthesia. Changes in heart rate, respiratory rate and rectal temperature in the animals treated with dexclamol were not different from those observed in the animals treated with droperidol. A comparison of the adrenolytic properties of dexclamol and droperidol was made on the isolated rabbit aortic strip. Both compounds produced a parallel shift to the right of the noradrenaline cumulative dose-response curves, indicating competitive antagonism. The pA2 values showed dexclamol to be approximately 15 times less potent than droperidol in inhibiting the noradrenaline-induced contraction of the rabbit aortic strip
Horizontal DNA Transfer Mechanisms of Bacteria as Weapons of Intragenomic Conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell–cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing “arms race. ” Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic’s effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell–cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated.
Cultural dimensions and social behavior correlates: Individualism-Collectivism and Power Distance.

This study presents the macrosocial and macropsychological correlates of two cultural dimensions, Individualism-Collectivism and Hierarchy, based on a review of cross-cultural research. Correlations between the culturelevel value scores provided by Hofstede, Schwartz and Trompenaars and nation-level indices confirm their criterion validity. Thus power distance and collectivism are correlated with low social development (HDI index), income differences (Gini index), the socio-political corruption index, and the competitiveness index. The predominantly Protestant societies are more individualist and egalitarian, the Confucianist societies are more collectivist; and Islamic soci
Citron kinase controls a molecular network required for midbody formation in cytokinesis

Cytokinesis partitions cytoplasmic and genomic materials at the end of cell division. Failure in this process causes polyploidy, which in turn can generate chromosomal instability, a hallmark of many cancers. Successful cytokinesis requires cooperative interaction between contractile ring and central spindle components, but how this cooperation is established is poorly understood. Here we show that Sticky (Sti), the Drosophila ortholog of the contractile ring component Citron kinase (CIT-K), interacts directly with two kinesins, Nebbish [the fly counterpart of human kinesin family member 14 (KIF14)] and Pavarotti [the Drosophila ortholog of human mitotic kinesin-like protein 1 (MKLP1)], and that in turn these kinesins interact with each other and with another central spindle protein, Fascetto [the fly ortholog of protein regulator of cytokinesis 1 (PRC1)]. Sti recruits Nebbish to the cleavage furrow, and both proteins are required for midbody formation and proper localization of Pavarotti and Fascetto. These functions require Sti kinase activity, indicating that Sti plays both structural and regulatory roles in midbody formation. Finally, we show that CIT-K’s role in midbody formation is conserved in human cells. Our findings indicate that CIT-K is likely to act at the top of the midbody-formation hierarchy by connecting and regulating a molecular network of contractile ring components and microtubule-associated proteins.
Faces of glory: the left-cheek posing bias for medallists of Brazilian jiu-jitsu competitions

ABSTRACT Laboratory studies have shown that people tend to show the left side of their face when asked to broadly express emotions, while they tend to show the right side when asked to hide emotions. Because emotions are expressed more intensely in the left side of the face, it is hypothesized that an individual’s intention to express or hide emotions biases the direction of lateral facial poses. The present study tested this hypothesis using photographic portraits of individuals experiencing emotional events in a naturalistic setting: the reception of medals in Brazilian jiu-jitsu competitions. Portrait photographs of Brazilian jiu-jitsu competitors were sourced online (N = 460) and were rated by two independent raters in terms of posing direction, emotional expression, and medal colour. Gold and silver medallists showed their left cheeks to the camera for commemorative photographs taken immediately after the medal ceremony. Positive emotions were expressed more often for gold medallists than silver ones. The left-cheek posing bias observed in the present study supports the hypothesis that the intended purpose of expressing or hiding emotions determines the direction of lateral posing biases, and extends the laboratory findings to situations in the real world.
Mutual Regulation of Receptor-Mediated Cell Signalling and Endocytosis: EGF Receptor System as an Example

© 2012 Wang, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mutual Regulation of Receptor-Mediated Cell Signalling and Endocytosis: EGF Receptor System as an Example
A wavelet based technique for suppression of EMG noise and motion artifact in ambulatory ECG

A wavelet-based denoising technique is investigated for suppressing EMG noise and motion artifact in ambulatory ECG. EMG noise is reduced by thresholding the wavelet coefficients using an improved thresholding function combining the features of hard and soft thresholding. Motion artifact is reduced by limiting the wavelet coefficients. Thresholds for both the denoising steps are estimated using the statistics of the noisy signal. Denoising of simulated noisy ECG signals resulted in an average SNR improvement of 11.4 dB, and its application on ambulatory ECG recordings resulted in L2 norm and max-min based improvement indices close to one. It significantly improved R-peak detection in both the cases.
Thermal energy harvesting circuit with maximum power point tracking control for self-powered sensor node applications

We present a simple implementation of a thermal energy harvesting circuit with the maximum power point tracking (MPPT) control for self-powered miniature-sized sensor nodes. Complex start-up circuitry and direct current to direct current (DC-DC) boost converters are not required, because the output voltage of targeted thermoelectric generator (TEG) devices is high enough to drive the load applications directly. The circuit operates in the active/asleep mode to overcome the power mismatch between TEG devices and load applications. The proposed circuit was implemented using a 0.35-μm complementary metal-oxide semiconductor (CMOS) process. Experimental results confirmed correct circuit operation and demonstrated the performance of the MPPT scheme. The circuit achieved a peak power efficiency of 95.5% and an MPPT accuracy of higher than 99%.
A Low-Cost Localization System Based on Artificial Landmarks

The present work proposes and evaluates a technique for improving the Turtlebot1 mobile robot localization system for navigation in unknown structured environments. In our proposal, the localization is refined by using a dense artificial landmark setup fixed in the environment ceiling. Although the use of artificial landmarks restricts the applicability of this methodology, the proposed methodology has the advantage of not depending on a previous mapping of the landmarks distribution in the environment, which makes its adoption a simple process.
Efficient solar-to-fuels production from a hybrid microbial–water-splitting catalyst system

Significance Renewable-fuels generation has emphasized water splitting to produce hydrogen and oxygen. For accelerated technology adoption, bridging hydrogen to liquid fuels is critical to the translation of solar-driven water splitting to current energy infrastructures. One approach to establishing this connection is to use the hydrogen from water splitting to reduce carbon dioxide to generate liquid fuels via a biocatalyst. We describe the integration of water-splitting catalysts comprised of earth-abundant components to wild-type and engineered Ralstonia eutropha to generate biomass and isopropyl alcohol, respectively. We establish the parameters for bacterial growth conditions at low overpotentials and consequently achieve overall efficiencies that are comparable to or exceed natural systems. Photovoltaic cells have considerable potential to satisfy future renewable-energy needs, but efficient and scalable methods of storing the intermittent electricity they produce are required for the large-scale implementation of solar energy. Current solar-to-fuels storage cycles based on water splitting produce hydrogen and oxygen, which are attractive fuels in principle but confront practical limitations from the current energy infrastructure that is based on liquid fuels. In this work, we report the development of a scalable, integrated bioelectrochemical system in which the bacterium Ralstonia eutropha is used to efficiently convert CO2, along with H2 and O2 produced from water splitting, into biomass and fusel alcohols. Water-splitting catalysis was performed using catalysts that are made of earth-abundant metals and enable low overpotential water splitting. In this integrated setup, equivalent solar-to-biomass yields of up to 3.2% of the thermodynamic maximum exceed that of most terrestrial plants. Moreover, engineering of R. eutropha enabled production of the fusel alcohol isopropanol at up to 216 mg/L, the highest bioelectrochemical fuel yield yet reported by >300%. This work demonstrates that catalysts of biotic and abiotic origin can be interfaced to achieve challenging chemical energy-to-fuels transformations.
Data dissemination using the energy map

One of the most important resources in wireless sensor networks is energy, since, in general, batteries cannot be recharged. The information about the amount of energy available at each part of the network is called the energy map and can be explored by routing algorithms. In this work, a new routing algorithm for wireless sensor networks is proposed. The key idea is to combine concepts presented in trajectory-based forwarding with the information provided by the energy map to determine routes in a dynamic fashion. Simulation results revealed that the energy spent with routing activity can be concentrated on nodes with high energy reserves, whereas low-energy nodes can use their energy only to perform sensing activity. In this manner, partitions of the network due to nodes that ran out of energy can be significantly delayed and the network lifetime extended.
Phylogenetic and Phylogenomic Definition of Rhizopus Species

Phylogenomic approaches have the potential to improve confidence about the inter-relationships of species in the order Mucorales within the fungal tree of life. Rhizopus species are especially important as plant and animal pathogens and bioindustrial fermenters for food and metabolite production. A dataset of 192 orthologous genes was used to construct a phylogenetic tree of 21 Rhizopus strains, classified into four species isolated from habitats of industrial, medical and environmental importance. The phylogeny indicates that the genus Rhizopus consists of three major clades, with R. microsporus as the basal species and the sister lineage to R. stolonifer and two closely related species R. arrhizus and R. delemar. A comparative analysis of the mating type locus across Rhizopus reveals that its structure is flexible even between different species in the same genus, but shows similarities between Rhizopus and other mucoralean fungi. The topology of single-gene phylogenies built for two genes involved in mating is similar to the phylogenomic tree. Comparison of the total length of the genome assemblies showed that genome size varies by as much as threefold within a species and is driven by changes in transposable element copy numbers and genome duplications.
CTCF-KDM4A complex correlates with histone modifications that negatively regulate CHD5 gene expression in cancer cell lines

Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5, and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood. Here, we show that CTCF and KDM4A form a protein complex, which is recruited into the first intron of CHD5. This is related to a decrease in H3K36me3/2 histone marks and is associated with its transcriptional downregulation. Depletion of CTCF or KDM4A by siRNA, triggered the reactivation of CHD5 expression, suggesting that both proteins are involved in the negative regulation of this gene. Furthermore, the knockout of KDM4A restored the CHD5 expression and H3K36me3 and H3K36me2 histone marks. Such mechanism acts independently of CHD5 promoter DNA methylation. Our findings support a novel mechanism of epigenetic repression at the gene body that does not involve promoter silencing.
Computational modelling of defects and charge trapping in amorphous and crystalline metal oxides

Thin ﬁlms of metal oxides, like Al₂O₃ and LaAlO₃, play a crucial role in emerging nanoelectronic devices. Using density functional theory (DFT) and other computational methods, the properties of defects and intrinsic polaron trapping have been calculated in LaAlO₃ and amorphous Al₂O₃. The spectroscopic properties of neutral (Vₒ⁰) and charged (Vₒ⁺) oxygen vacancies in cubic and rhombohedral LaAlO₃ have been investigated using Time Dependent DFT and the embedded cluster method. The peaks of the optical absorption spectra are predicted at 3.5 and 4.2 eV for Vₒ⁰ and 3.6 eV for Vₒ⁺ in rhombohedral LaAlO₃. The calculated electron paramagnetic resonance (EPR) parameters of Vₒ⁺ accurately predict the width (3 mT) and position of its EPR spectrum. Amorphous Al₂O₃ is then investigated, which has applications in non-volatile memory and a-IGZO (amorphous indium-gallium-zinc oxide) thin ﬁlm transistors. Amorphous Al₂O₃ structures were generated using a molecular dynamics melt-quench approach and found to be in good agreement with experiment. DFT calculations, using a tuned hybrid functional, determined that the a-Al₂O₃ band gap decreases to 5.5 eV, compared to 8.6 eV in α-Al₂O₃, because of the reduction in Al coordination number in the amorphous phase. This causes a shift in the electrostatic potential that lowers the conduction band minimum, adding support to experimental measurements of band offsets. Then intrinsic polaron and bipolaron trapping in a-Al₂O₃ is modelled. The average trapping energy of hole polarons in a-Al₂O₃ was calculated to be 1.26 eV, much higher than the 0.38 eV calculated for α-Al₂O₃. Electrons were found not to trap in both crystalline and amorphous Al₂O₃. To explain the negative charging of Al₂O₃ films the properties of oxygen, hydrogen and aluminium defects were calculated. A mechanism is proposed to explain experimental trap spectroscopy measurements, whereby negatively charge defects are compensated by positively charged defects that have unoccupied states in the band gap. These predictions will facilitate experimental identification of defect states in LaAlO₃ and Al₂O₃ and their effect on nanodevices.