Miracle-dz/UniFAR-FTUs huggingface dataset:
Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair

Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most difficult to treat tumors, including those that are hypoxic, radio-resistant, or deep-seated. Clinical data, mostly from Japan and Germany, are promising, with favorable oncologic outcomes and acceptable toxicity. In this manuscript, we review the physical and biological rationales for CIRT, with an emphasis on DNA damage and repair, as well as providing a comprehensive overview of the translational and clinical data using CIRT.
Optimization via Low-rank Approximation, with Applications to Community Detection in Networks

Community detection is one of the fundamental problems of network analysis. A number of methods for community detection have been proposed, including spectral clustering, modularity, and likelihood-based methods. Most of these methods have to solve an optimization problem over a discrete set of labels, which is computationally infeasible. Some fast algorithms have been proposed for specific methods or models have been proposed, but only on a case by case basis. Here we propose a general approach for maximizing a function of a network adjacency matrix over discrete labels by projecting the set of labels onto a subspace spanned by leading eigenvectors of the adjacency matrix. The main idea is that projection onto a low-dimensional space makes the feasible set of labels much smaller and the optimization problem much easier. We prove a general result on this method and show how to apply it to several previously proposed community detection criteria, establishing its consistency for label estimation in each case. Simulations and applications to real-world data are included to demonstrate our method performs well for multiple problems over a wide range of parameters.
Phase Transformations of Nanocrystalline Martensitic Materials

The physical phenomena and engineering applications of martensitic phase transformations are the focus of intense ongoing research. The martensitic phase transformation and functional properties such as the shape-memory effect and superelasticity are strongly affected by the crystal size at the nanoscale. The current state of research on the impact of crystal size on the phase stability of the martensite is reviewed summarizing experimental results of various nanostructured martensitic materials and discussing the corresponding theoretical approaches. The review outlines the effects of crystal size on the complex morphology of the martensite, leading to interface structures not encountered in coarse-grained bulk materials. The unique shape-memory properties of martensitic materials can persist even at the nanoscale. Nanocrystalline martensitic materials can be processed to obtain tailored functional properties in combination with enhanced strength. Structural changes of metallic nanowires are similar to those arising by martensitic phase transformations and also can lead to shape-memory effects, as predicted by atomistic simulations.
Different ATM Signaling in Response to Chromium(VI) Metabolism via Ascorbate and Nonascorbate Reduction: Implications for in Vitro Models and Toxicogenomics

Background Carcinogenic hexavalent chromium [Cr(VI)] requires cellular reduction to generate DNA damage. Metabolism of Cr(VI) by its principal reducer ascorbate (Asc) lacks a Cr(V) intermediate, which is abundant in reactions with a minor reducing agent, glutathione. Cultured cells are widely used in mechanistic studies of Cr(VI) toxicity; however, they typically contain < 1% of normal Asc levels. Asc deficiency is also expected to diminish protection against reactive oxygen species. Objectives We assessed how the presence of Asc in cells affects their stress signaling and survival responses to chromate. Methods We investigated the effects of Asc restoration in human lung H460 cells and normal human lung fibroblasts on the activation and functional role of ATM kinase, which controls DNA damage responses involving several hundreds of proteins. Results Treatment of standard cultures with Cr(VI) strongly activated ATM, as indicated by its automodification at Ser1981 and by phosphorylation of checkpoint kinase 2 (CHK2) and chromatin/transcription regulator KRAB-associated protein 1 (KAP1). Confirming the importance of activated ATM, its inhibition impaired replication recovery and clonogenic survival. In contrast, fully Asc-restored cells lacked ATM activation by Cr(VI), and ATM silencing produced no significant effects on p53 stabilization, apoptosis, replication recovery, or clonogenic survival. Dose dependence studies found a close correlation between ATM activation and the extent of Cr(VI) reduction by glutathione. Conclusions Asc restoration in cultured cells dramatically altered their stress responses to Cr(VI) by preventing activation of the oxidant-sensitive ATM network. We suggest that toxicogenomic and other cell response-based approaches likely underestimate Cr(VI) genotoxicity when standard ATM-activating carcinogens are used as references. Citation Luczak MW, Green SE, Zhitkovich A. 2016. Different ATM signaling in response to chromium(VI) metabolism via ascorbate and nonascorbate reduction: implications for in vitro models and toxicogenomics. Environ Health Perspect 124:61–66; http://dx.doi. org/10.1289/ehp.1409434
Pruning Rogue Taxa Improves Phylogenetic Accuracy: An Efficient Algorithm and Webservice

Abstract The presence of rogue taxa (rogues) in a set of trees can frequently have a negative impact on the results of a bootstrap analysis (e.g., the overall support in consensus trees). We introduce an efficient graph-based algorithm for rogue taxon identification as well as an interactive webservice implementing this algorithm. Compared with our previous method, the new algorithm is up to 4 orders of magnitude faster, while returning qualitatively identical results. Because of this significant improvement in scalability, the new algorithm can now identify substantially more complex and compute-intensive rogue taxon constellations. On a large and diverse collection of real-world data sets, we show that our method yields better supported reduced/pruned consensus trees than any competing rogue taxon identification method. Using the parallel version of our open-source code, we successfully identified rogue taxa in a set of 100 trees with 116 334 taxa each. For simulated data sets, we show that when removing/pruning rogue taxa with our method from a tree set, we consistently obtain bootstrap consensus trees as well as maximum-likelihood trees that are topologically closer to the respective true trees.
A Decentralized Receiver in Gaussian Interference

Bounds are developed on the maximum communications rate between a transmitter and a fusion node aided by a cluster of distributed receivers with limited resources for cooperation, all in the presence of an additive Gaussian interferer. The receivers cannot communicate with one another and can only convey processed versions of their observations to the fusion center through a Local Array Network (LAN) with limited total throughput. The effectiveness of each bound’s approach for mitigating a strong interferer is assessed over a wide range of channels. It is seen that, if resources are shared effectively, even a simple quantize-and-forward strategy can mitigate an interferer 20 dB stronger than the signal in a diverse range of spatially Ricean channels. Monte-Carlo experiments for the bounds reveal that, while achievable rates are stable when varying the receiver’s observed scattered-path to line-of-sight signal power, the receivers must adapt how they share resources in response to this change. The bounds analyzed are proven to be achievable and are seen to be tight with capacity when LAN resources are either ample or limited.
Direct current plasma jet at atmospheric pressure operating in nitrogen and air

An atmospheric pressure direct current (DC) plasma jet is investigated in N2 and dry air in terms of plasma properties and generation of active species in the active zone and the afterglow. The influence of working gases and the discharge current on plasma parameters and afterglow properties are studied. The electrical diagnostics show that discharge can be sustained in two different operating modes, depending on the current range: a self-pulsing regime at low current and a glow regime at high current. The gas temperature and the N2 vibrational temperature in the active zone of the jet and in the afterglow are determined by means of emission spectroscopy, based on fitting spectra of N2 second positive system (C3Π-B3Π) and the Boltzmann plot method, respectively. The spectra and temperature differences between the N2 and the air plasma jet are presented and analyzed. Space-resolved ozone and nitric oxide density measurements are carried out in the afterglow of the jet. The density of ozone, which is formed.
Changes in User Perceptions of a Telemedicine System Over Time: From Initial Implementation to Everyday Use.

BACKGROUND Benefits associated with telemedicine are contingent upon positive user perceptions. Despite this, research on user perceptions of telemedicine remains limited. INTRODUCTION Usability approaches offer a robust way to assess user perceptions, but have rarely been applied in telemedicine. In this study, a usability approach was employed to examine how user perceptions toward a telemedicine system changed over the course of everyday use. MATERIALS AND METHODS A telemedicine system was introduced to a hospital in the home service. Ten mobile nurses completed the System Usability Scale (SUS) after initial use, then again after 18 months of everyday use. Results were compared. Analysis included Bangor et al.'s (2009) adjective rating scale. RESULTS The initial SUS mean was 83 (standard deviation [SD] = 7.98), indicating "excellent" usability. After 18 months, the SUS mean was 64.38, indicating "OK" usability (SD = 14.25, p < 0.05, 95% confidence interval [CI]). Over time, users had lower desire to use the system frequently (p < 0.05, 95% CI), found it more complex (p < 0.05, 95% CI), and perceived greater inconsistency in its design (p < 0.05, 95% CI). DISCUSSION Considered with existing evidence, our usability findings indicate that a temporary period of positive user perceptions occurs when new telemedicine systems are used for the first few months. This fades with everyday use, with design inconsistency and perceived complexity becoming more noticeable. Although other factors such as user satisfaction and efficiency may also contribute, further studies are needed for confirmation. CONCLUSIONS User perceptions of telemedicine vary with time. To help maximize the benefits and longevity of telemedicine systems, responding to intermittent user appraisal is desirable.
First do no harm – The impact of financial incentives on dental x-rays 1

This paper assesses the impact of dentist remuneration on the incidence of potentially harmful dental x-rays. We use unique panel data which provide details of 1.3 million treatment claims by Scottish NHS dentists made between 1998 and 2007. Controlling for unobserved heterogeneity of both patients and dentists we estimate a series of fixed-effects models that are informed by a theoretical model of x-ray delivery and identify the effects on dental x-raying of dentists moving from a fixed salary to fee-for-service and patients moving from co-payment to exemption. We establish that there are significant increases in x-rays when dentists receive fee for service rather than salary payments and patients are made exempt from payment. There are further increases in x-rays when a patient switches to a fee for service dentist relative to them switching to a salaried one. JEL Code I11.
A Comparison between Two Post-Failure Load Distribution Techniques with Multiple Routing Configurations

When a link fails in an IP network, the network re-converges to redirect the traffic away from the failed link. IP fast reroute is used to minimize the time taken to redirect the traffic to an alternate path. Multiple routing configurations (MRC) is the IP fast reroute scheme under consideration. In this paper, we will discuss how to minimize the impact of the MRC recovery process on the post failure load distribution over network links. Two techniques used to achieve a good load distribution across links after failure are compared. The first technique utilizes manual link weight manipulation with MRC. The second technique is the modified MRC. Both advantages and disadvantages of the two techniques are discussed.
Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease.

PURPOSE To compare the expression of the pro- and anti-inflammatory forms of interleukin (IL)-1 in the tear fluid and conjunctival epithelium of normal eyes and those with dry-eye disease. METHODS The concentrations of IL-1 alpha, IL-1 beta (precursor and mature forms), and IL-1 receptor antagonist (IL-1Ra) were measured by ELISA in tear fluid samples obtained from normal individuals and patients with dry eye who had rosacea-associated meibomian gland disease (MGD) or Sjögren's syndrome (SS) aqueous tear deficiency (ATD). These cytokines were also measured in normal tear fluid before and after nasal stimulation to induce reflex tearing. The relative expression of these cytokines was evaluated in conjunctival impression cytology specimens and conjunctival biopsy tissue obtained from normal subjects and SS ATD-affected patients using immunofluorescent staining. Matrix metalloproteinase (MMP)-9 concentration and activity in the tear fluid were evaluated with gelatin zymography and with an MMP-9 activity assay kit, respectively. RESULTS Compared with normal subjects, the concentration of IL-1 alpha and mature IL-1 beta in the tear fluid was increased, and the concentration of precursor IL-1 beta was decreased in patients with MGD (P < 0.05, P = 0.02, and P < 0.01, respectively) and SS ATD (P < 0.001, P = 0.02, and P < 0.001, respectively). There was no significant change in the concentration of IL-1 alpha, precursor IL-1 beta, and IL-1Ra in reflex tear fluid, indicating that the lacrimal glands may secrete these cytokines. The activity of MMP-9, a physiological activator of IL-1 beta, was significantly elevated in the tear fluid of both dry-eye groups compared with normal subjects. A strong positive correlation was observed between the intensity of corneal fluorescein staining and the tear fluid IL-1 alpha concentration (r(2) = 0.17, P < 0.02) and the mature-to-precursor IL-1 beta ratio (r(2) = 0.46, P < 0.001). Positive immunofluorescent staining for IL-1 alpha, mature IL-1 beta, and IL-1Ra was observed in a significantly greater percentage of conjunctival cytology specimens from eyes with SS ATD than in those from normal eyes (P < 0.01 for IL-1 alpha, P < 0.009 for mature IL-1 beta, and P < 0.05 for IL-1Ra). CONCLUSIONS Dry-eye disease is accompanied by an increase in the proinflammatory forms of IL-1 (IL-1 alpha and mature IL-1 beta) and a decrease in the biologically inactive precursor IL-1 beta in tear fluid. Increased protease activity on the ocular surface may be one mechanism by which precursor IL-1 beta is cleaved to the mature, biologically active form. The conjunctival epithelium appears to be one source of the increased concentration of IL-1 in the tear fluid of patients with dry-eye disease. These results suggest that IL-1 may play a key role in the pathogenesis of keratoconjunctivitis sicca.
Structural Characterization of the Binding Interactions of Various Endogenous Estrogen Metabolites with Human Estrogen Receptor α and β Subtypes: A Molecular Modeling Study

In the present study, we used the molecular docking approach to study the binding interactions of various derivatives of 17β-estradiol (E2) with human estrogen receptor (ER) α and β. First, we determined the suitability of the molecular docking method to correctly predict the binding modes and interactions of two representative agonists (E2 and diethylstilbesterol) in the ligand binding domain (LBD) of human ERα. We showed that the docked structures of E2 and diethylstilbesterol in the ERα LBD were almost exactly the same as the known crystal structures of ERα in complex with these two estrogens. Using the same docking approach, we then characterized the binding interactions of 27 structurally similar E2 derivatives with the LBDs of human ERα and ERβ. While the binding modes of these E2 derivatives are very similar to that of E2, there are distinct subtle differences, and these small differences contribute importantly to their differential binding affinities for ERs. In the case of A-ring estrogen derivatives, there is a strong inverse relationship between the length of the hydrogen bonds formed with ERs and their binding affinity. We found that a better correlation between the computed binding energy values and the experimentally determined logRBA values could be achieved for various A-ring derivatives by re-adjusting the relative weights of the van der Waals interaction energy and the Coulomb interaction energy in computing the overall binding energy values.
Circumstances Preceding Homicide-Suicides Involving Child Victims: A Qualitative Analysis

Homicide-suicide incidents involving child victims can have a detrimental impact on survivors of the violence, family members and friends of the decedents, and other community members, but the rare occurrence of these acts makes using quantitative data to examine their associated antecedents challenging. Therefore, using qualitative data from the 2003-2011 National Violent Death Reporting System, we examined 175 cases of homicide-suicide involving child victims in an effort to better understand the complex situational factors of these events. Our findings indicate that 98% of homicide-suicides with child victims are perpetrated by adults (mostly parents) and propelled by the perpetrators’ intimate partner problems, mental health problems, and criminal/legal problems. These events are often premeditated, and plans for the violence are sometimes disclosed prior to its occurrence. Findings provide support for several theoretical perspectives, and implications for prevention are discussed.
Experimental characterization of the tensile failure mode of ultra-thin chopped carbon fiber tape-reinforced thermoplastics

Ultra-thin chopped carbon fiber tape-reinforced thermoplastics, which belong to a class of randomly oriented strands and are characterized by enhanced strength, stiffness, and formability properties, have been prepared via a paper-making method from ultra-thin thermoplastic prepregs. The failure of ultra-thin chopped carbon fiber tape-reinforced thermoplastics under static tensile loading was studied in detail using various observation techniques, such as high-speed camera imaging, thermography, and optical microscopy. The obtained results revealed that the tensile fracture of ultra-thin chopped carbon fiber tape-reinforced thermoplastics exhibited three main patterns: fiber breakage, splitting of chopped tapes, and pulling out of chopped tapes. In contrast to conventional randomly oriented strands, the utilization of ultra-thin prepregs decreased the tensile strength scattering. An increase in the ultra-thin prepreg tape length resulted in an increase in the strength average magnitude, reaching saturation at a length of 18 mm. The results of this study can be used for constructing tensile strength prediction models and expanding the ultra-thin chopped carbon fiber tape-reinforced thermoplastics application range.
Looking for the Holy Grail of Software Development

The history of software engineering has been marked by many famous project failures documented in papers, articles, and books. This pattern of lack of success has prompted the creation of dozens of software analysis, requirements definition, design methods, programming languages, software development environments, and software development processes all promoted as solving "the software problem. " What we hear less about are software projects that were successful. This article reports on the findings of an extensive analysis of successful software projects that have been reported in the literature. It discusses the different interpretations of success and extracts the characteristics that successful projects have in common. These characteristics provide software project managers with an agenda of topics to be addressed that will help ensure, not guarantee, that their software project will be successful.
Fast (mainly 30–100 Hz) oscillations in the cat cerebellothalamic pathway and their synchronization with cortical potentials

1 Intracellular recordings from 216 thalamocortical (TC) neurones in the ventrolateral (VL) nucleus of intact‐cortex and decorticated cats under ketamine–xylazine anaesthesia revealed spontaneously occurring fast oscillations (mainly 30–100 Hz) in 86% of investigated cells. The fast depolarizing events consisted of excitatory postsynaptic potentials (EPSPs), giving rise to fast prepotentials (FPPs) in 22% of neurones, which eventually lead to full‐blown action potentials. The frequency of fast events changed by factors of 2–5 in periods as short as 0.3–1.0 s. 2 The spontaneous oscillations were similar to responses evoked in VL relay neurones by stimuli to the afferent cerebellofugal axons in brachium conjunctivum (BC) and were strikingly reduced or abolished after electrolytic lesion of BC axons. 3 The amplitude and duration of fast depolarizing events were significantly reduced during the descending phase of the inhibitory postsynaptic potentials (IPSPs) in TC cells, related to spontaneous spindles or evoked by local thalamic stimulation. 4 Averaged field potentials recorded from motor cortex and triggered by EPSPs and/or action potentials of intracellularly recorded VL cells demonstrated that both spontaneous and BC‐evoked fast depolarizations in VL relay neurones were coherent with fast rhythms in cortical area 4. 5 These results show that, in addition to the thalamic and cortical generation sites of the fast (so‐called gamma) oscillations, prethalamic relay stations, such as deep cerebellar nuclei, are major contributors to the induction of fast rhythms which depend on the depolarization of thalamic and cortical neurones and which represent a hallmark of brain activation patterns.
Evening exposure to blue light stimulates the expression of the clock gene PER2 in humans

We developed a non‐invasive method to measure and quantify human circadian PER2 gene expression in oral mucosa samples and show that this gene oscillates in a circadian (= about a day) fashion. We also have the first evidence that induction of human PER2 expression is stimulated by exposing subjects to 2 h of light in the evening. This increase in PER2 expression was statistically significant in comparison to a non‐light control condition only after light at 460 nm (blue) but not after light exposure at 550 nm (green). Our results indicate that the non‐image‐forming visual system is involved in human circadian gene expression. The demonstration of a functional circadian machinery in human buccal samples and its response to light opens the door for investigation of human circadian rhythms at the gene level and their associated disorders.