Miracle-dz/UniFAR-FTUs huggingface dataset:
Incorporating NTCP into Randomized Trials of Proton Versus Photon Therapy

Purpose: We propose and simulate a model-based methodology to incorporate heterogeneous treatment benefit of proton therapy (PrT) versus photon therapy into randomized trial designs. We use radiation-induced pneumonitis (RP) as an exemplar. The aim is to obtain an unbiased estimate of how predicted difference in normal tissue complications probability (ΔNTCP) converts into clinical outcome on the patient level. Materials and Methods: ΔNTCP data from in silico treatment plans for photon therapy and PrT for patients with locally advanced lung cancer as well as randomly sampled clinical risk factors were included in simulations of trial outcomes. The model used at point of analysis of the trials was an iQUANTEC model. Trial outcomes were examined with Cox proportional hazards models, both in case of a correctly specified model and in a scenario where there is discrepancy between the dose metric used for ΔNTCP and the dose metric associated with the “true” clinical outcome, that is, when the model is misspecified. We investigated how outcomes from such a randomized trial may feed into a model-based estimate of the patient-level benefit from PrT, by creating patient-specific predicted benefit probability distributions. Results: Simulated trials showed benefit in accordance with that expected when the NTCP model was equal to the model for simulating outcome. When the model was misspecified, the benefit changed and we observed a reversal when the driver of outcome was high-dose dependent while the NTCP model was mean-dose dependent. By converting trial results into probability distributions, we demonstrated large heterogeneity in predicted benefit, and provided a randomized measure of the precision of individual benefit estimates. Conclusions: The design allows for quantifying the benefit of PrT referral, based on the combination of NTCP models, clinical risk factors, and traditional randomization. A misspecified model can be detected through a lower-than-expected hazard ratio per predicted ΔNTCP.
Biochemical Characterization of Streptococcus pneumoniae Penicillin-Binding Protein 2b and Its Implication in β-Lactam Resistance

ABSTRACT Extensive use of β-lactam antibiotics has led to the selection of pathogenic streptococci resistant to β-lactams due to modifications of the penicillin-binding proteins (PBPs). PBP2b from Streptococcus pneumoniae is a monofunctional (class B) high-molecular-weight PBP catalyzing the transpeptidation between adjacent stem peptides of peptidoglycan. The transpeptidase domain of PBP2b isolated from seven clinical resistant (CR) strains contains 7 to 44 amino acid changes over the sequence of PBP2b from the R6 β-lactam-sensitive strain. We show that the extracellular soluble domains of recombinant PBP2b proteins (PBP2b*) originating from these CR strains have an in vitro affinity for penicillin G that is reduced by up to 99% from that of the R6 strain. The Thr446Ala mutation is always observed in CR strains and is close to the key conserved motif (S443SN). The Thr446Ala mutation in R6 PBP2b* displays a 60% reduction in penicillin G affinity in vitro compared to that for the wild-type protein. A recombinant R6 strain expressing the R6 PBP2b Thr446Ala mutation is twofold less sensitive to piperacillin than the parental S. pneumoniae strain. Analysis of the Thr446Ala mutation in the context of the PBP2b CR sequences revealed that its influence depends upon the presence of other unidentified mutations.
Sisymbrium Officinale (L.) Scop. and its Polyphenolic Fractions Inhibit the Mutagenicity of Tert‐Butylhydroperoxide in Escherichia Coli WP2uvrAR Strain

One Sisymbrium officinale (L.) Scop. aqueous dry extract (SOE) and its polyphenolic fractions (Fb, Fc, Fd and Fe) were evaluated for their ability to inhibit the oxidative mutagenicity of tert‐butylhydroperoxide in the Ames test. The possible involvement of desmutagenic and/or bioantimutagenic mechanisms was evaluated by applying a three‐time based protocol (pre‐treatment, co‐treatment and post‐treatment). Furthermore, some protective antioxidant mechanisms were investigated. The total polyphenol and flavonol amount was also determined, and the fingerprint was outlined by high‐performance thin‐layer chromatography and densitometry. SOE, Fb and Fe exhibited strong antimutagenicity against tert‐butylhydroperoxide in all treatment protocols, this suggesting the involvement of both desmutagenic and bioantimutagenic mechanisms. These samples also showed antioxidant properties, including neutralization of the superoxide anion, lipid peroxidation inhibition and chelation and reduction of iron. Fb and Fe were rich in polyphenols and flavonols, so suggesting a possible role of these compounds in the antimutagenicity. Taking into account that oxidative stress is responsible for the damage of various environmental toxicants, particularly tobacco smoke, present results can support the traditional use of hedge mustard by smokers to restore the vocal cord function affected by the oxidative damage and suggest a possible application of SOE and its fractions as food supplements. Copyright © 2016 John Wiley & Sons, Ltd.
Effect of human chorionic gonadotropin on preovulatory luteinizing hormone surge and ovarian hormone secretion in gilts.

The influence of varying doses of human chorionic gonadotropin (hCG) on the preovulatory luteinizing hormone (LH) surge, estradiol-17 beta (E2) and progesterone (P4) was studied in synchronized gilts. Altrenogest (AT) was fed (15 mg X head-1 X d-1) to 24 cyclic gilts for 14 d. Pregnant mares serum gonadotropin (PMSG; 750 IU) was given im on the last day of AT feeding. The gilts were then assigned to one of four groups (n = 6): saline (I), 500 IU hCG (II), 1,000 IU hCG (III) and 1,500 IU hCG (IV). Human chorionic gonadotropin or saline was injected im 72 h after PMSG. No differences in ovulation rate or time from last feeding of AT to occurrence of estrus were observed. All gilts in Groups I and II expressed a preovulatory LH surge compared with only four of six and three of six in Groups III and IV, respectively. All groups treated with hCG showed a rapid drop (P less than .01) in plasma levels of E2 11, 17, 23 h after hCG injection when compared with the control group (35 h). The hCG-treated gilts exhibited elevated P4 concentrations 12 h earlier than the control group (3.1 +/- .5, 3.4 +/- .72, 3.1 +/- .10 ng/ml in groups II, III and IV at 60 h post-hCG vs .9 +/- .08 ng/ml in group I; P less than .05). These studies demonstrate that injections of ovulatory doses of hCG (500 to 1,500 IU) had three distinct effects on events concomitant with occurrence of estrus in gilts: decreased secretion of E2 immediately after hCG administration, failure to observe a preovulatory LH surge in some treated animals and earlier production of P4 by newly developed corpora lutea.
EASURES B ASED ON C IRCULAR S ECTORS

With growing number of stored image data, image search and image similarity problem become more and more important. The answer can be solved by Content-Based Image Retrieval systems. This paper deals with an image search using similarity measures based on circular sectors method. The method is inspired by human eye functionality. The main contribution of the paper is a modified method that increases accuracy for about 8% in comparison with original approach. Here proposed method has used HSB colour model and median function for feature extraction. The original approach uses RGB colour model with mean function. Implemented method was validated on 10 image categories where overall average precision was 67%.
The effect of flap thickness on corneal biomechanics after myopic laser in situ keratomileusis using the M-2 microkeratome

Purpose The purpose of this study was to determine the effect of flap thickness on corneal biomechanics after myopic laser in situ keratomileusis (LASIK). Methods This is a prospective controlled non-randomized, institutional study. Patients underwent either epi-LASIK with mitomycin (advanced surface ablation [ASA]), thin-flap LASIK (90 µm head), or thick-flap LASIK (130 µm head). In ASA, the Moria Epi-K hydroseparator was used. LASIK flaps were created using the Moria M-2 mechanical microkeratome. The corneal hysteresis (CH) and corneal resistance factor (CRF) were measured preoperatively and 3 months after surgery, using the Ocular Response Analyzer®. Results Ten patients (19 eyes) underwent ASA, 11 patients (16 eyes) underwent thin-flap LASIK, and 11 patients (16 eyes) underwent thick-flap LASIK. The mean preoperative CH was 10.47±0.88, 10.52±1.4, and 11.28±1.4 mmHg (p=0.043), respectively, decreasing after surgery by 1.75±1.02, 1.66±1.00, and 2.62±1.03 mmHg (p=0.017). The mean reduction of CH per micron of central corneal ablation was 0.031, 0.023, and 0.049 mmHg/µm (p=0.005). Mean preoperative CRF was 10.11±1.28, 10.34±1.87, and 10.62±1.76 mmHg (p=0.66), decreasing after surgery by 2.33±1.35, 2.77±1.03, and 2.92±1.10 mmHg (p=0.308). The mean reduction of CRF per micron of central corneal ablation was 0.039, 0.040, and 0.051 mmHg/µm (p=0.112). Conclusion Thick-flap LASIK caused a greater reduction of CH and CRF than thin-flap LASIK and ASA, although this was statistically significant only for CH. ASA and thin-flap LASIK were found to be biomechanically similar.
Lessons from ICT design of a healthcare worker-centered system for a chronic mental care hospital

We report on designing natural ICT tools and solutions for integration into a non-ICT workflow at a Brazilian chronic care Center. Our healthcare worker-centered approach for continuous life-care contrasts from the more typical acute care situations that tend to be patient-centered or administrator-centered. Chronic mental care focuses on improving patients' life quality as they age in contrast to acute care. Therapy is collaboratively preparing patients to establish a routine for a normal life. Our main findings from our worker-centered design are: 1. Supporting workers communication and workflow using an online social intranet is effective, 2. Designing for appropriation as well as adoption is important and 3. Public workflow visualization can influence workers behavior. Our approach may apply to other long-term assistant scenarios as nursing homes, teaching and parenting.
Perception of Stiffness in Laparoscopy - the Fulcrum Effect

We explored how the perception of stiffness can be distorted in Minimally Invasive Surgery. We combined a mechanical simulator with a haptic device, and implemented linear springs at the tip of the simulated laparoscopic device. To explore the influence of mechanical advantage on perception, we set different values of the ratio between internal and external length of the tool. We found that a nonsymmetrical ratio causes bias in the perceived stiffness when novice tangential probing is compared to radial probing. In contrast, haptic experts did not show similar perceptual bias.
Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S

We report the discovery of very-high-energy (VHE) γ-ray emission of the binary system PSR B1259−63/SS 2883 of a radio pulsar orbiting a massive, luminous Be star in a highly eccentric orbit. The observations around the 2004 periastron passage of the pulsar were performed with the four 13 m Cherenkov telescopes of the HESS experiment, recently installed in Namibia and in full operation since December 2003. Between February and June 2004, a γ-ray signal from the binary system was detected with a total significance above 13σ. The flux was found to vary significantly on timescales of days which makes PSR B1259−63 the first variable galactic source of VHE γ-rays observed so far. Strong emission signals were observed in pre- and post-periastron phases with a flux minimum around periastron, followed by a gradual flux decrease in the months after. The measured time-averaged energy spectrum above a mean threshold energy of 380 GeV can be fitted by a simple power law F0(E/ 1T eV) −Γ with a photon index Γ= 2.7 ± 0.2stat ± 0.2sys and flux normalisation F0 = (1.3 ± 0.1stat ± 0.3sys) × 10 −12 TeV −1 cm −2 s −1 . T his detection of VHE γ-rays provides unambiguous evidence for particle acceleration to multi-TeV energies in the binary system. In combination with coeval observations of the X-ray synchrotron emission by the RXTE and INTEGRAL instruments, and assuming the VHE γ-ray emission to be produced by the inverse Compton mechanism, the magnetic field strength can be directly estimated to be of the order of 1 G.
Minor Type IV Collagen α5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1

Type IV collagens (Col IV), components of basement membrane, are essential in the maintenance of tissue integrity and proper function. Alteration of Col IV is related to developmental defects and diseases, including cancer. Col IV α chains form α1α1α2, α3α4α5 and α5α5α6 protomers that further form collagen networks. Despite knowledge on the functions of major Col IV (α1α1α2), little is known whether minor Col IV (α3α4α5 and α5α5α6) plays a role in cancer. It also remains to be elucidated whether major and minor Col IV are functionally redundant. We show that minor Col IV α5 chain is indispensable in cancer development by using α5(IV)-deficient mouse model. Ablation of α5(IV) significantly impeded the development of KrasG12D-driven lung cancer without affecting major Col IV expression. Epithelial α5(IV) supports cancer cell proliferation, while endothelial α5(IV) is essential for efficient tumor angiogenesis. α5(IV), but not α1(IV), ablation impaired expression of non-integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung cancer cells and endothelial cells phenocopied the cells deficient of α5(IV). Constitutively active DDR1 or MEK1 rescued the defects of α5(IV)-ablated cells. Thus, minor Col IV α5(IV) chain supports lung cancer progression via DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV can not be functionally compensated by abundant major Col IV.
Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant rhodopsin.

PURPOSE Mutations at various loci on the rhodopsin gene have been shown to cause autosomal dominant retinitis pigmentosa (ADRP). One of the most common is a point mutation (P23H) near the N-terminus of the protein. The authors have studied the effects of light deprivation on the rate of degeneration in pigmented transgenic mice expressing the P23H mutation as well as two additional mutations near the N-terminus of opsin (V20G, P27L). METHODS Transgenic and normal littermates were reared in darkness or in cyclic light (approximately 7 foot-candle) for periods of 2, 4, or 6 months. Retinal structure and function were evaluated by electroretinography, retinal densitometry, light microscopy, and TUNEL labeling. RESULTS Retinas of normal animals, whether reared in darkness or in cyclic light, had no structural or functional abnormalities. The rate of photoreceptor degeneration in dark-reared transgenic mice was significantly slower than in transgenic mice raised under cyclic light conditions. Differences between the two groups of animals were evident in the retinal histology, the electroretinographically determined sensitivity to photic stimulation, and the rhodopsin levels in the retina. TUNEL labeling of retinal wholemounts showed that cyclic light-reared animals had a threefold higher incidence of photoreceptor cell death than their dark-reared counterparts; the density of apoptotic cells was greatest in the inferior retina, the region most severely affected in patients with the P23H mutation. In comparison, photoreceptor cell death was more uniformly distributed across the retina in dark-reared transgenic mice. CONCLUSIONS These findings suggest that light activation of rhodopsin contributes to the severity of the degenerative disease resulting from the P23H opsin mutation, and they raise the possibility that minimizing exposure to light may help to prolong useful vision of patients with this form of retinitis pigmentosa.
High-level Synthesis-based signal coding

The extremely populated state of current ICs have motivated for advanced High-level Synthesis techniques to be used for specialized circuits. Due to the complexity and lack of flexibility of existing High-level Synthesis tools, most of the low level circuits such as signal coding blocks were left out of the EDA scope and to the responsibility of layout engineers. In this paper we present a High-level Synthesis approach which is suitable for both complex and low level custom block design. The advantage of this approach is a uniform and formal treatment of both high-level and low-level design, as well as provably correct results.
Bilinguals’ processing of lexical cues in L1 and L2: an eye-tracking study

Abstract This study seeks to understand how bilinguals process texts with lexical cues in their first language (L1) and second language (L2) using an eye-tracking methodology. Quantitative data were obtained from an eye-tracker and a post-test, while qualitative data were gathered through interviews with the participants. The findings from the eye-tracking results indicate that the participants’ fixations were similar on novel words accompanied by their L1 cues and those accompanied by their L2 cues. When comparing the participants’ fixation on L1 and L2 cues, the findings show that the participants spent similar time on both types of cues. The use of L1 cues leads to a similar amount of acquisition of novel words when compared to the use of L2 cues. The study makes two contributions to research in language learning: Methodologically, the use of eye-tracking is discussed along with how it may be triangulated with other methods for studying language processing. Empirically, the study sheds light on how bilinguals process cues in their L1 and L2. Implications for future research and classroom practice are considered.
Map of technology: Topic modelling full-text patent data

A number of studies have focused on creating patent maps (Yoon et al. 2002; Lee et al. 2009; Kim et al. 2008). Many of the patent map studies rely on traditional bibliometrics, such as Karki (1997) using citation analysis to form a patent mapping to public policy analysis and Daim et al. (2006) shows what can be regarded as the de facto bibliometric technology forecasting example. Recently the focus has turned to the use big data and data mining, specifically text mining, in patent mapping. In 2007, Tseng, Lin and Lin (2007) illustrated text mining techniques for patent analysis. Tseng, Wang, Lin and Lin (2007) focused on creating machine produced summarizations and mapping of patents. A data mining approach has also been used in technology roadmapping (Yoon and Phaal 2013). As computational methods in the machine-learning field are becoming more available and stable, studies have moved towards using stable processes and focusing on applying the methods to for example management of technology. For example, unsupervised learning methods, such as Latent Dirichlet Allocation, are relatively stable methods relatively easily accessed by science scholars outside the computer domain. In this study, we show the capabilities of unsupervised learning with a single-node computer in learning the thematic areas of all full-text patent documents published by the USPTO in 2014 (N=374,704). We further discuss the key challenges in running the study, interpreting the outcome and further developments.
Large vocabulary decoding and confidence estimation using word posterior probabilities

The paper investigates the estimation of word posterior probabilities based on word lattices and presents applications of these posteriors in a large vocabulary speech recognition system. A novel approach to integrating these word posterior probability distributions into a conventional Viterbi decoder is presented. The problem of the robust estimation of confidence scores from word posteriors is examined and a method based on decision trees is suggested. The effectiveness of these techniques is demonstrated on the broadcast news and the conversational telephone speech corpora where improvements both in terms of word error rate and normalised cross entropy were achieved compared to the baseline HTK evaluation systems.
Rate-distortion dimension of stochastic processes

The rate-distortion dimension (RDD) of an analog stationary process is studied as a measure of complexity that captures the amount of information contained in the process. It is shown that the RDD of a process, defined as two times the asymptotic ratio of its rate-distortion function R(D) to log 1/D as the distortion D approaches zero, is equal to its information dimension (ID). This generalizes an earlier result by Kawabata and Dembo and provides an operational approach to evaluate the ID of a process, which previously was shown to be closely related to the effective dimension of the underlying process and also to the fundamental limits of compressed sensing. The relation between RDD and ID is illustrated for a piecewise constant process.
Performance issues of H . 264 compressed video streams over IEEE 802 . 11 b based MANETs

This paper addresses the problem of video streams transmission in IEEE 802.11b based Mobile Ad-hoc Networks (MANET). Through the study of the delivery of a live encoded video stream, we expose the characteristics of different routing protocols and the infeasibility to provide QoS. The analysis shows the impact of a MANET on H.264 real-time video flows in terms of packet loss, end-to-end delay, jitter and distortion, and the behavior of H.264 error resilience tools in order to determine their effectiveness on such network scenarios. The results show that video traffic has demands that are hard to be met by a standard MANET, and that improvements are required in terms of routing protocols and QoS provisioning either on the MAC layer or at IP level using traffic shaping tools. Also, most of H.264 error resilience tools are not so effective as expected with this kind of networks, being the random macroblock updating the most effective one we have tested.
Nonparametric Willingness-to-pay Measures and Confidence Statements

Willingness to pay (WTP) for a health care program can be estimated in contingent valuation (CV) studies by a nonparametric approach. The nonparametric approach is free from distributional assumptions, which is a strength compared with parametric regression-based approaches. However, using a nonparametric approach it is not clear how to obtain confidence statements for WTP estimates, for example, when testing hypotheses regarding differences in mean WTP for different subsamples. The authors propose a procedure that allows statistical testing and confidence interval estimation by employing bootstrap techniques. The method is easy to implement and has low computational costs with modern personal computers. The method is applied to data from a CV study where the WTP for hormone replacement therapy was investigated. The mean WTP was estimated for the full sample and separately for women with mild and severe menopausal symptoms. Using the proposed method, the mean WTP was significantly higher in the group with severe symptoms. Key words: bootstrap; economic evaluation; hormone replacement therapy; nonparametric; willingness to pay. (Med Decis Making 1998;18:330-336)