Miracle-dz/UniFAR-FTUs huggingface dataset:
TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1

The abortive activity of topoisomerases can result in clastogenic and/or lethal DNA damage in which the topoisomerase is covalently linked to the 3′- or 5′-terminus of a DNA strand break. This type of DNA damage is implicated in chromosome translocations and neurological disease and underlies the clinical efficacy of an important class of anticancer topoisomerase ‘poisons’. Tyrosyl DNA phosphodiesterase-1 protects cells from abortive topoisomerase I (Top1) activity by hydrolyzing the 3′-phosphotyrosyl bond that links Top1 to a DNA strand break and is currently the only known human enzyme that displays this activity in cells. Recently, we identified a second tyrosyl DNA phosphodiesterase (TDP2; aka TTRAP/EAPII) that possesses weak 3′-tyrosyl DNA phosphodiesterase (3′-TDP) activity, in vitro. Herein, we have examined whether TDP2 contributes to the repair of Top1-mediated DNA breaks by deleting Tdp1 and Tdp2 separately and together in murine and avian cells. We show that while deletion of Tdp1 in wild-type DT40 cells and mouse embryonic fibroblasts decreases DNA strand break repair rates and cellular survival in response to Top1-induced DNA damage, deletion of Tdp2 does not. However, deletion of both Tdp1 and Tdp2 reduces rates of DNA strand break repair and cell survival below that observed in Tdp1−/− cells, suggesting that Tdp2 contributes to cellular 3′-TDP activity in the absence of Tdp1. Consistent with this idea, over-expression of human TDP2 in Tdp1−/−/Tdp2−/−/− DT40 cells increases DNA strand break repair rates and cell survival above that observed in Tdp1−/− DT40 cells, suggesting that Tdp2 over-expression can partially complement the defect imposed by loss of Tdp1. Finally, mice lacking both Tdp1 and Tdp2 exhibit greater sensitivity to Top1 poisons than do mice lacking Tdp1 alone, further suggesting that Tdp2 contributes to the repair of Top1-mediated DNA damage in the absence of Tdp1. In contrast, we failed to detect a contribution for Tdp1 to repair Top2-mediated damage. Together, our data suggest that Tdp1 and Tdp2 fulfil overlapping roles following Top1-induced DNA damage, but not following Top2-induced DNA damage, in vivo.
Automated process planning: reasoning from first principles based on geometric relation constraints

While previous work in automated process planning established plan ordering on an empirical basis alone, we derive our process plans based on the Holding-Under-Uncertainty Principle. We will introduce the principle, and we will describe the operational requirements needed to make this principle implementable in practice. The principle takes into account the form and geometric tolerances needed to locate features in deriving plan steps. Rather than just focusing on technological features, our planning strategy is controlled by the geometric relationships among features. By implementing a constraint propagation paradigm, we ensure that the tolerances accumulated in generating the part geometry remain within the tolerances specified by the design.
An In Vitro Study of Horizontal Connections in the Intermediate Layer of the Superior Colliculus

Some models propose that the spatial and temporal distributions of premotor activity in the intermediate layer of the superior colliculus are shaped by neuronal ensembles that give rise to local excitatory and distant inhibitory connections. One function proposed for these connections is to mediate a “winner-take-all” network; the short-range excitatory connections build up the activity of neighboring cells that command orienting movements in one direction, whereas the wide-ranging inhibitory projections attenuate the activity of remote cells that command incompatible movements. We used in vitro photostimulation and whole-cell patch-clamp recording to test these models by measuring the spatial extent of synaptic interactions within the rat intermediate layer. Uncaging glutamate over whole-cell patch-clamped cells in the intermediate layer elicited long-lasting inward currents, resulting from direct activation of glutamate receptors expressed by the cells, and brief synaptic currents evoked by activation of presynaptic neurons. The synaptic responses comprised clusters of excitatory and inhibitory currents. The size of these responses depended on the location of the stimulus with respect to the clamped cell. Large responses were commonly evoked by stimuli within 200 μm of the soma in the intermediate layer; smaller responses could occasionally be evoked from sites as distant as 500 μm. Responses evoked by stimulation beyond this distance were rare. Although the results demonstrated powerful local excitatory and inhibitory connections, they did not support the pattern of short-range excitation and widespread inhibition predicted by the winner-take-all hypothesis.
Aggregation of Markovian Models -- An Alternating Least Squares Approach

To deal with the problem of state space explosion in Markovian models often compositional modeling and the aggregation of components are used. Several approximate aggregation methods exist which are usually based on heuristics. This paper presents a new aggregation approach for Markovian components which computes aggregates that minimize the difference according to some algebraically defined function which describes the difference between the component and the aggregate. If the difference becomes zero, aggregation is exact and component and aggregate are indistinguishable. Approximate aggregates are computed using an alternating least squares approach which tries to minimize the norm-wise difference between the original component and the aggregate. The approach is extended to generate bounding aggregates which allow one to compute bounds on transient or stationary quantities when the aggregate is embedded in an environment.
Exploring a SNR/molecular cloud association within HESS J1745-303

HESS J1745-303 is an extended, unidentified VHE (very high energy) gamma-ray source discovered using HESS in the Galactic Plane Survey. Since no obvious counterpart has previously been found in longer-wavelength data, the processes that power the VHE emission are not well understood. Combining the latest VHE data with recent XMM-Newton observations and a variety of source catalogs and lower-energy survey data, we attempt to match (from an energetic and positional standpoint) the various parts of the emission of HESS J1745-303 with possible candidates. Though no single counterpart is found to fully explain the VHE emission, we postulate that at least a fraction of the VHE source may be explained by a supernova-remnant/molecular-cloud association and/or a high-spin-down-flux pulsar.
Age differences in verbal short-term memory and the process of redintegration

This study explored age related differences in short term memory, specifically the process of redintegration. Redintegration was uniquely defined by examining the word length effect and associative word pairs. Twenty younger adults and twenty older adults were instructed to remember short lists of words in eight different recall conditions which varied in level of difficulty. Task difficulty was defined using the following variables: irrelevant speech, presentation rate (1 vs. 2 seconds), and recall condition (immediate vs. delayed). Findings revealed recall was higher for younger adults compared with older adults in all recall conditions. Furthermore, as the difficulty of the memory task increased, strong redintegrative effects were observed for word length and associative word pairs for both the younger and older adults. Meaning, short words were better remembered than long words and associative word pairs were better remembered than unrelated word pairs.
Emotional reactivity in infants with congenital heart defects: findings from a large case‐cohort study in Norway

Aim: Advances in medical treatment in recent years have led to dramatically improved survival rates of children with severe congenital heart defects (CHD). However, very little is known about the psychological consequences for these children, particularly during and after the early period of invasive treatment. In this study, we investigated the extent to which the severity of the CHD affects the child’s emotional reactivity at 6 months of age.
Efficiency Through Eavesdropping: Link-layer Packet Caching

The broadcast nature of wireless networks is the source of both their utility and much of their complexity. To turn what would otherwise be unwanted interference into an advantage, this paper examines an entirely backwards-compatible extension to the 802.11 link-layer protocol for making use of overheard packets, called RTS-id. RTS-id operates by augmenting the standard 802.11 RTS/CTS process with a packet ID check, so that if the receiver of an RTS message has already received the packet in question, it can inform the sender and bypass the data transmission entirely. We present the design, implementation, and evaluation of RTS-id on a real hardware platform that provides a DSP-programmable 802.11 radio. While limited in scale due to restricted availability of the CalRadio platform, our testbed experiments demonstrate that RTS-id can reduce air time usage by 25.2% in simple 802.11b infrastructure deployments on real hardware, even when taking into account all of the protocol overhead. Additionally, we present trace-based simulations demonstrating the potential savings on the MIT Roofnet mesh network. In particular, RTS-id provides a 12% decrease in the number of expected data transmissions for a median path, and over 25% reduction for more than 10% of Roofnet paths.
DAG-aware AIG rewriting: a fresh look at combinational logic synthesis

This paper presents a technique for preprocessing combinational logic before technology mapping. The technique is based on the representation of combinational logic using and-inverter graphs (AIGs), a networks of two-input ANDs and inverters. The optimization works by alternating DAG-aware AIG rewriting, which reduces area by sharing common logic without increasing delay, and algebraic AIG balancing, which minimizes delay without increasing area. The new technology-independent flow is implemented in a public-domain tool ABC. Experiments on large industrial benchmarks show that the proposed methodology scales to very large designs and is several orders of magnitude faster than SIS and MVSIS while offering comparable or better quality when measured by the quality of the network after mapping
Herpes Simplex Virus 1 ICP4 Forms Complexes with TFIID and Mediator in Virus-Infected Cells

ABSTRACT The infected cell polypeptide 4 (ICP4) of herpes simplex virus 1 (HSV-1) is a regulator of viral transcription that is required for productive infection. Since viral genes are transcribed by cellular RNA polymerase II (RNA pol II), ICP4 must interact with components of the pol II machinery to regulate viral gene expression. It has been shown previously that ICP4 interacts with TATA box-binding protein (TBP), TFIIB, and the TBP-associated factor 1 (TAF1) in vitro. In this study, ICP4-containing complexes were isolated from infected cells by tandem affinity purification (TAP). Forty-six proteins that copurified with ICP4 were identified by mass spectrometry. Additional copurifying proteins were identified by Western blot analysis. These included 11 components of TFIID and 4 components of the Mediator complex. The significance of the ICP4-Mediator interaction was further investigated using immunofluorescence and chromatin immunoprecipitation. Mediator was found to colocalize with ICP4 starting at early and continuing into late times of infection. In addition, Mediator was recruited to viral promoters in an ICP4-dependent manner. Taken together, the data suggest that ICP4 interacts with components of TFIID and Mediator in the context of viral infection, and this may explain the broad transactivation properties of ICP4.
Cross Media Exposure and Visual Search

When people are exposed to a stimulus be it consciously or unconsciously their perceptions of the stimuli tend to improve. This phenomenon has been observed in many a study and dubbed the ​mere exposure effect. ​The effect has been noted to influence impressions of stimuli and even influence decisions people make. The effect has proven incredibly robust positively influencing human perceptions of drawing, nonsense words, and even faces of people from other racial groups. Similarly, studies in eye gaze show that positive perception can affect unconscious and conscious eye movements. That people tend to took at items they like even when instructed to look at items they dislike this is presented in the ​Gaze cascade model and plays a small part in what is known as ​gaze bias​. However, there is little documentation on if or how these phenomena work together, if the exposure effect can manipulate gaze. Furthermore, the studies mentioned focus heavily on same media exposure. Here we analyze cross media exposure’s effect on gaze during a visual search. In doing so offering new insight on how exposure, positive​ ​preference,​ ​and​ ​eye​ ​gaze​ ​interact.
Traffic and power-aware protection scheme in Elastic Optical Networks

Currently, the need for “greener” telecommunication networks is stimulating research efforts to find new solutions to cope with power consumption and sustainability issues. Exploiting the potential of optical Wavelength Division Multiplexed (WDM) networks for this purpose has been identified as an attractive approach. However, the traditional WDM fixed-grid, where 50 GHz-spaced optical carriers are used with Single Line Rates (SLR), may result in lower efficiency from both the spectral occupation and power consumption perspectives. Higher flexibility can be provided by adopting Mixed Line Rates (MLR) and, especially, the so-called Elastic Optical Network (EON) paradigm, which is enabled by the Orthogonal Frequency Division Multiplexing combined with Coherent Detection (CO-OFDM). In this scenario a finer channel spacing is considered so the spectrum can be best fitted to actual traffic needs. Another critical issue is the network robustness to failures, accomplished by reserving additional resources as a backup for protection. Traditional approaches allocate dedicated (1+1) resources for protection and the peak-rate capacity is reserved in both working and protection paths for every traffic demand. Thus, the power consumed in resilient network is substantially increased compared to the unprotected case. In this paper, we evaluate the impact of the hourly network traffic variation to reduce the power consumed by backup resources, by adapting their rate to the current required bandwidth. We apply this paradigm to the SLR, MLR and EON scenarios and find that, especially in the EON case and for high traffic load conditions, substantial energy savings (up to 27%) can be obtained by exploiting the information on hourly traffic variation.
Inflammation, Biomarkers and Immuno-Oncology Pathways in Pancreatic Cancer

It is estimated that pancreatic cancer will be the second leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options for this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are not completely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, relatively poorer antigenicity compared to other solid tumors, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological, would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored.
EEG-informed fMRI analysis during a hand grip task: estimating the relationship between EEG rhythms and the BOLD signal

In the last decade, an increasing interest has arisen in investigating the relationship between the electrophysiological and hemodynamic measurements of brain activity, such as EEG and (BOLD) fMRI. In particular, changes in BOLD have been shown to be associated with changes in the spectral profile of neuronal activity, rather than with absolute neural power. On the other hand, though, recent findings showed that different EEG rhythms are independently related to changes in the BOLD signal: therefore, it would be important to distinguish between the contributions of the different EEG rhythms to BOLD fluctuations when modeling the relationship between EEG and BOLD. Here we proposed a novel method to perform EEG-informed fMRI analysis, so that the EEG regressors take into account both the changes in the spectral profile and the rhythms distinction. We applied it to EEG-fMRI data during a bimanual motor task in healthy subjects, and compared the results with those obtained by regressing fMRI data onto a single regressor covering the entire range of frequencies, ignoring the distinction between different EEG rhythms. Our results showed that the proposed method better captures the correlations between BOLD signal and EEG rhythms modulations, identifying task-related well localized activated volumes.
Hierarchical Rule Generalization with Automatically Derived Multi-level Word Classes for MT

Hierarchical rule generalization is a central aspect of Chiang’s hierarchical decoding model. “Hierarchical substitution” is the process by which generalized rules are used in decoding. We believe that hierarchical substitutions of semantically similar words are more likely to be grammatically well-formed than hierarchical substitutions of arbitrary words. In this paper, we extend the rule generalization process to use a hierarchy of semantic bilingual word classes, which are derived automatically using a bilingual semantic similarity score. The result is that during decoding, hierarchical substitution of semantically specific classes (e.g., the class of colors) will have a higher probability than hierarchical substitution of more general classes (e.g., the class containing all words). Although we achieved a substantial increase in the number of generalized rules used during decoding, more investigation is required to determine how this will improve MT scores (BLEU) over those generated by the standard rule generalization process.
Functional Adaptation of a Plant Receptor- Kinase Paved the Way for the Evolution of Intracellular Root Symbioses with Bacteria

Nitrogen-fixing root nodule symbioses (RNS) occur in two major forms—Actinorhiza and legume-rhizobium symbiosis—which differ in bacterial partner, intracellular infection pattern, and morphogenesis. The phylogenetic restriction of nodulation to eurosid angiosperms indicates a common and recent evolutionary invention, but the molecular steps involved are still obscure. In legumes, at least seven genes—including the symbiosis receptor-kinase gene SYMRK—are essential for the interaction with rhizobia bacteria and for the Arbuscular Mycorrhiza (AM) symbiosis with phosphate-acquiring fungi, which is widespread in occurrence and believed to date back to the earliest land plants. We show that SYMRK is also required for Actinorhiza symbiosis of the cucurbit Datisca glomerata with actinobacteria of the genus Frankia, revealing a common genetic basis for both forms of RNS. We found that SYMRK exists in at least three different structural versions, of which the shorter forms from rice and tomato are sufficient for AM, but not for functional endosymbiosis with bacteria in the legume Lotus japonicus. Our data support the idea that SYMRK sequence evolution was involved in the recruitment of a pre-existing signalling network from AM, paving the way for the evolution of intracellular root symbioses with nitrogen-fixing bacteria.
Structured Input-Output Lasso, with Application to eQTL Mapping, and a Thresholding Algorithm for Fast Estimation

We consider the problem of learning a high-dimensional multi-task regression model, under sparsity constraints induced by presence of grouping structures on the input covariates and on the output predictors. This problem is primarily motivated by expression quantitative trait locus (eQTL) mapping, of which the goal is to discover genetic variations in the genome (inputs) that influence the expression levels of multiple co-expressed genes (outputs), either epistatically, or pleiotropically, or both. A structured input-output lasso (SIOL) model based on an intricate l1/l2-norm penalty over the regression coefficient matrix is employed to enable discovery of complex sparse input/output relationships; and a highly efficient new optimization algorithm called hierarchical group thresholding (HiGT) is developed to solve the resultant non-differentiable, non-separable, and ultra high-dimensional optimization problem. We show on both simulation and on a yeast eQTL dataset that our model leads to significantly better recovery of the structured sparse relationships between the inputs and the outputs, and our algorithm significantly outperforms other optimization techniques under the same model. Additionally, we propose a novel approach for efficiently and effectively detecting input interactions by exploiting the prior knowledge available from biological experiments.
Phytochemical analysis and antioxidant potential of the leaves of Garcinia travancorica Bedd.

Phytochemical analysis of the leaves of Garcinia travancorica, a hitherto uninvestigated endemic species to the Western Ghats of south India, resulted in isolation and characterisation of the polyisoprenylated benzophenones 7-epi-nemorosone (1) and garcinol (2) along with biflavonoids GB-1a (3), GB-1 (4), GB-2 (5), morelloflavone (6) and morelloflavone-7″-O-β-d-glycoside or fukugiside (7). The compounds were identified using various spectroscopic techniques, mainly through NMR and MS. The methanol extract and the biflavonoids 3, 4, 5 and 7 showed potential in vitro antioxidant activities. The IC50 value of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of compound 7 was 8.34 ± 2.12 μg/mL, comparable to that of standard ascorbic acid (3.2 ± 0.50 μg/mL). In the superoxide radical scavenging assay, compound 7 gave IC50 value of 6.95 ± 1.33 μg/mL close to standard ascorbic acid with IC50 value of 5.8 ± 0.25 μg/mL. Validated HPTLC estimation revealed G. travancorica as a rich source of morelloflavone-7″-O-β-d-glycoside (7.12% dry wt. leaves).
Statistical methods in epidemiology: I. Statistical errors in hypothesis testing.

PURPOSE Although scientific journal editors are making use of statisticians in the review process, the quality of statistical reporting in many journals remains poor. In many cases the problem for the scientist would appear to be a lack of understanding of basic statistics. The focus of the scientist is on showing 'p < 0.05', when what is actually required is a statement about effect size and interval estimation. The aim of this paper is to show the inadequacy of reporting of results using p-values alone. This paper is the first in a series detailing common statistical methods, with a view to aiding potential authors in their statistical presentation of data. METHOD A review of the basic hypothesis test, using examples from the author's own teaching experiences. RESULTS Type I and type II errors are defined; the problem of multiple comparisons is highlighted; interval estimation is introduced. CONCLUSIONS The case for considering the p-value as an error probability is made which suggests ways of improving statistical presentation and thus expediting the statistical review process.