Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation Analysis of Cell-Free DNA and Single Circulating Tumor Cells in Metastatic Breast Cancer Patients with High Circulating Tumor Cell Counts

Purpose: The purpose of this study was to directly compare mutation profiles in multiple single circulating tumor cells (CTC) and cell-free DNA (cfDNA) isolated from the same blood samples taken from patients with metastatic breast cancer (MBC). We aimed to determine whether cfDNA would reflect the heterogeneity observed in 40 single CTCs. Experimental Design: CTCs were enumerated by CELLSEARCH. CTC count was compared with the quantity of matched cfDNA and serum CA15-3 and alkaline phosphatase (ALP) in 112 patients with MBC. In 5 patients with ≥100 CTCs, multiple individual EpCAM-positive CTCs were isolated by DEPArray and compared with matched cfDNA and primary tumor tissue by targeted next-generation sequencing (NGS) of about 2,200 mutations in 50 cancer genes. Results: In the whole cohort, total cfDNA levels and cell counts (≥5 CTCs) were both significantly associated with overall survival, unlike CA15-3 and ALP. NGS analysis of 40 individual EpCAM-positive CTCs from 5 patients with MBC revealed mutational heterogeneity in PIK3CA, TP53, ESR1, and KRAS genes between individual CTCs. In all 5 patients, cfDNA profiles provided an accurate reflection of mutations seen in individual CTCs. ESR1 and KRAS gene mutations were absent from primary tumor tissue and therefore likely either reflect a minor subclonal mutation or were acquired with disease progression. Conclusions: Our results demonstrate that cfDNA reflects persisting EpCAM-positive CTCs in patients with high CTC counts and therefore may enable monitoring of the metastatic burden for clinical decision-making. Clin Cancer Res; 23(1); 88–96. ©2016 AACR.
The Effect of Paternal Age on Outcome in Assisted Reproductive Technology Using the Ovum Donation Model

Objective: To determine the effect of paternal age (PA) on implantation and live birth rates in an ovum donation program. Design: Retrospective study. Methods: A total of 237 ovum donor cycles were reviewed. All donors were stimulated with gonadotrophin-releasing hormone agonist (GnRHa) downregulation and human menopausal gonadotropin. Recipients were prepared with GnRHa downregulation and estradiol/progesterone replacement. Embryo transfers were done at blastocyst stage under ultrasound guidance. The effect of PA on outcome was analyzed controlling for number and grade of embryos transferred. Outcome was not pregnant (NP), spontaneous abortion (SAb), and live births (LBs). Results: Of the 237 cycles, 36 resulted in NP (15.2%), 39 in SAb (16.5%), and 162 in LB (68.4%). The mean PA (MPA) was significantly different between the 3 groups, and implantation rates also declined with increasing MPA (P =.01). Overall, the mean number and grade of embryos transferred were 2.1 ± 0.4 and 1.3 ± 0.4, respectively. The NP couples had more embryos of poorer grade than SAb and LB couples (P <.05), but there were no differences between SAb and NP couples (P >.85). Logistic regression analysis demonstrated a 26% lower odds of live birth rate with each 5-year increase in PA (P =.01). Conclusions: Advanced PA has an adverse impact on assisted reproductive technology (ART) outcome. After adjusting for number and embryo grades transferred, a younger PA has a more favorable ART outcome.
Modeling the effects of delayed haptic and visual feedback in a collaborative virtual environment

Collaborative virtual environments (CVEs) enable two or more people, separated in the real world, to share the same virtual “space. ” They can be used for many purposes, from teleconferencing to training people to perform assembly tasks. Unfortunately, the effectiveness of CVEs is compromised by one major problem: the delay that exists in the networks linking users together. Whilst we have a good understanding, especially in the visual modality, of how users are affected by delayed feedback from their own actions, little research has systematically examined how users are affected by delayed feedback from other people, particularly in environments that support haptic (force) feedback. The current study addresses this issue by quantifying how increasing levels of latency affect visual and haptic feedback in a collaborative target acquisition task. Our results demonstrate that haptic feedback in particular is very sensitive to low levels of delay. Whilst latency affects visual feedback from 50 ms, it impacts on haptic task performance 25 ms earlier, and causes the haptic measures of performance deterioration to rise far more steeply than visual. The “impact-perceive-adapt” model of user performance, which considers the interaction between performance measures, perception of latency, and the breakdown of perception of immediate causality, is proposed as an explanation for the observed pattern of performance.
Saturn's Small Inner Satellites: Clues to Their Origins

Cassini images of Saturn's small inner satellites (radii of less than ∼100 kilometers) have yielded their sizes, shapes, and in some cases, topographies and mean densities. This information and numerical N-body simulations of accretionary growth have provided clues to their internal structures and origins. The innermost ring-region satellites have likely grown to the maximum sizes possible by accreting material around a dense core about one-third to one-half the present size of the moon. The other small satellites outside the ring region either may be close to monolithic collisional shards, modified to varying degrees by accretion, or may have grown by accretion without the aid of a core. We derived viscosity values of 87 and 20 square centimeters per second, respectively, for the ring material surrounding ring-embedded Pan and Daphnis. These moons almost certainly opened their respective gaps and then grew to their present size early on, when the local ring environment was thicker than it is today.
Clinical and cost-effectiveness of a new nurse-led continence service: a randomised controlled trial.

BACKGROUND Continence services in the UK have developed at different rates within differing care models, resulting in scattered and inconsistent services. Consequently, questions remain about the most cost-effective method of delivering these services. AIM To evaluate the impact of a new service led by a continence nurse practitioner compared with existing primary/secondary care provision for people with urinary incontinence and storage symptoms. DESIGN OF STUDY Randomised controlled trial with a 3- and 6-month follow-up in men and women (n = 3746) aged 40 years and over living in private households (intervention [n = 2958]; control [n = 788]). SETTING Leicestershire and Rutland, UK. METHOD The continence nurse practitioner intervention comprised a continence service provided by specially trained nurses delivering evidence-based interventions using predetermined care pathways. They delivered an 8-week primary intervention package that included advice on diet and fluids; bladder training; pelvic floor awareness and lifestyle advice. The standard care arm comprised access to existing primary care including GP and continence advisory services in the area. Outcome measures were recorded at 3 and 6 months post-randomisation. RESULTS The percentage of individuals who improved (with at least one symptom alleviated) at 3 months was 59% in the intervention group compared with 48% in the standard care group (difference of 11%, 95% CI = 7 to 16; P<0.001) The percentage of people reporting no symptoms or 'cured' was 25% in the intervention group and 15% in the standard care group (difference of 10%, 95% CI = 6 to 13, P = 0.001). At 6 months the difference was maintained. There was a significant difference in impact scores between the two groups at 3 and 6 months. CONCLUSIONS The continence nurse practitioner-led intervention reduced the symptoms of incontinence, frequency, urgency and nocturia at 3 and 6 months; impact was reduced; and satisfaction with the new service was high.
Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.
The Rod Pathway of the Microbat Retina Has Bistratified Rod Bipolar Cells and Tristratified AII Amacrine Cells

We studied the retinal rod pathway of Carollia perspicillata and Glossophaga soricina, frugivorous microbats of the phyllostomid family. Protein kinase Cα (PKCα) immunolabeling revealed abundant rod bipolar cells (RBCs) with axon terminals in the innermost sublamina of the inner plexiform layer (IPL), which is typical for mammals. Extraordinarily, the RBC axons showed additional synaptic contacts in a second sublamina further out in the IPL. Dye injections of PKCα-prelabeled RBCs of C. perspicillata confirmed the bistratified axon morphology. The functional partition of the IPL into ON and OFF sublayers was shown by using antibodies against vesicular glutamate transporter 1 [labeling all ON and OFF bipolar cell (BC) axon terminals] and G-protein γ13 (labeling all ON BCs). The ON sublayer occupied 75% of the IPL thickness, including both strata of the RBC axons. RBC output onto putative AII amacrine cells (ACs), the crucial interneurons of the rod pathway, was identified by calretinin, PKCα, and CtBP2 triple immunolabeling. Dye injections of calretinin-prelabeled ACs revealed tristratification of the AII ACs corresponding to the bistratified RBCs. Triple immunolabeling for PKCα, nitric oxide synthetase (NOS), and either GABAC or CtBP2 indicated GABAergic feedback onto RBCs via NOS-immunoreactive ACs. AII output analysis showed glycineric synapses with glycine receptor α1 expression between AII cells and OFF cone BCs and connexin 36-labeled gap junctions between AII cells and ON cone BCs. We conclude that microbats have a well developed rod pathway with great similarities to that of other mammals, but with an unusual IPL stratification pattern of RBCs and AIIs.
Cytotoxicity and secondary metabolites production in terrestrial Nostoc strains, originating from different climatic/geographic regions and habitats: Is their cytotoxicity environmentally dependent?

Extensive selection of cyanobacterial strains (82 isolates) belonging to the genus Nostoc, isolated from different climatic regions and habitats, were screened for both their secondary metabolite content and their cytotoxic effects to mammalian cell lines. The overall occurrence of cytotoxicity was found to be 33%, which corresponds with previously published data. However, the frequency differs significantly among strains, which originate from different climatic regions and microsites (particular localities). A large fraction of intensely cytotoxic strains were found among symbiotic strains (60%) and temperate and continental climatic isolates (45%); compared with the less significant incidences in strains originating from cold regions (36%), deserts (14%), and tropical habitats (9%). The cytotoxic strains were not randomly distributed; microsites that clearly had a higher occurrence of cytotoxicity were observed. Apparently, certain natural conditions lead to the selection of cytotoxic strains, resulting in a high cytotoxicity occurrence, and vice versa. Moreover, in strains isolated from a particular microsite, the cytotoxic effects were caused by different compounds. This result supports our hypothesis for the environmental dependence of cytotoxicity. It also contradicts the hypothesis that clonality and lateral gene transfer could be the reason for this phenomenon. Enormous variability in the secondary metabolites was detected within the studied Nostoc extracts. According to their molecular masses, only 26% of these corresponded to any known structures; thus, pointing to the high potential for the use of many terrestrial cyanobacteria in both pharmacology and biotechnology. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011.
Ambient Stable Quantitative PCR Reagents for the Detection of Yersinia pestis

Background Although assays for detecting Yersinia pestis using TaqMan probe-based real-time PCR have been developed for years, little is reported on room-temperature-stable PCR reagents, which will be invaluable for field epidemic surveillance, immediate response to public health emergencies, counter-bioterrorism investigation, etc. In this work, a set of real-time PCR reagents for rapid detection of Y. pestis was developed with extraordinary stability at 37°C. Methods/Principal Findings TaqMan-based real-time PCR assays were developed using the primers and probes targeting the 3a sequence in the chromosome and the F1 antigen gene caf1 in the plasmid pMT1of Y. pestis, respectively. Then, carbohydrate mixtures were added to the PCR reagents, which were later vacuum-dried for stability evaluation. The vacuum-dried reagents were stable at 37°C for at least 49 days for a lower concentration of template DNA (10 copies/µl), and up to 79 days for higher concentrations (≥102 copies/µl). The reagents were used subsequently to detect soil samples spiked with Y. pestis vaccine strain EV76, and 5×104 CFU per gram of soil could be detected by both 3a- and caf1-based PCR reagents. In addition, a simple and efficient method for soil sample processing is presented here. Conclusions/Significance The vacuum-dried reagents for real-time PCR maintain accuracy and reproducibility for at least 49 days at 37°C, indicating that they can be easily transported at room temperature for field application if the machine for performing real-time PCR is available. This dry reagent is of great significance for routine plague surveillance.
Kingman's coalescent and Brownian motion.

We describe a simple construction of Kingman’s coalescent in terms of a Brownian excursion. This construction is closely related to, and sheds some new light on, earlier work by Aldous [3] and Warren [23]. Our approach also yields some new results: for instance, we obtain the full multifractal spectrum of Kingman’s coalescent. This complements earlier work on Beta-coalescents by the authors and Schweinsberg [7]. Surprisingly, the thick part of the spectrum is not obtained by taking the limit as α → 2 in the result for Beta-coalescents mentioned above. Other analogies and differences between the case of Beta-coalescents and Kingman’s coalescent are discussed.
Heterogeneity of tbpB, the transferrin-binding protein B gene, among serogroup B Neisseria meningitidis strains of the ET-5 complex

ET-5 complex strains of Neisseria meningitidis were traced intercontinentally and have been causing hyperendemic meningitis on a worldwide scale. In an attempt to develop a fully broad cross-reactive transferrin-binding protein B (TbpB)-based vaccine, we undertook to assess the extent of variability of TbpB proteins among strains of this epidemiological complex. For this purpose, a PCR-based method was developed to study the heterogeneity of the tbpB genes from 31 serogroup B N. meningitidis strains belonging to the ET-5 complex. To define adequate primers, the tbpB gene from an ET-5 complex strain, 8680 (B:15:P1.3; isolated in Chile in 1987), was cloned and the nucleotide sequence was determined and compared to two other previously published tbpB sequences. A tbpB fragment was amplified from genomic DNA from each of the 31 strains. By this method, heterogeneity in size was observed and further characterized by restriction pattern analysis with four restriction enzymes and by sequencing tbpB genes from three other ET-5 complex strains. Four distinct tbpB gene types were identified. Fifty-five percent of the strains studied (17/31) harbored tbpB genes similar to that of strain BZ83 (B:15:-) isolated in The Netherlands in 1984. Ten of the 31 strains (32.2%) had tbpB genes close to that of strain M982. Only 3 of the 31 (9.6%) were found to harbor tbpB genes close to that of strain 8680, and finally one strain, 8710 (B:15:P1.3; isolated in Chile in 1987), was found to harbor a tbpB gene different from all the others. These results demonstrated a pronounced variability among tbpB alleles within a limited number of ET-5 complex strains collected over a 19-year period. Despite the genetic heterogeneity observed, specific antisera raised to purified Tbps from ET-5 complex strains showed broad cross-reactivity between different TbpBs both by Western blot analysis and bactericidal assay, confirming that a limited number of TbpB molecules included in a vaccine are likely to induce broadly cross-reactive antibodies against the different strains.
Risk Sensitive Path Integral Control

Recently path integral methods have been developed for stochastic optimal control for a wide class of models with non-linear dynamics in continuous space-time. Path integral methods find the control that minimizes the expected cost-to-go. In this paper we show that under the same assumptions, path integral methods generalize directly to risk sensitive stochastic optimal control. Here the method minimizes in expectation an exponentially weighted cost-to-go. Depending on the exponential weight, risk seeking or risk averse behaviour is obtained. We demonstrate the approach on risk sensitive stochastic optimal control problems beyond the linear-quadratic case, showing the intricate interaction of multi-modal control with risk sensitivity.
On Fairness in Secure Computation

Secure computation is a fundamental problem in modern cryptography in which multiple parties join to compute a function of their private inputs without revealing anything beyond the output of the function. A series of very strong results in the 1980’s demonstrated that any polynomial-time function can be computed while guaranteeing essentially every desired security property. The only exception is the fairness property, which states that no player should receive their output from the computation unless all players receive their output. While it was shown that fairness can be achieved whenever a majority of players are honest, it was also shown that fairness is impossible to achieve in general when half or more of the players are dishonest. Indeed, it was proven that even boolean XOR cannot be computed fairly by two parties. The fairness property is both natural and important, and as such it was one of the first questions addressed in modern cryptography (in the context of signature exchange). One contribution of this thesis is to survey the many approaches that have been used to guarantee different notions of partial fairness. We then revisit the topic of fairness within a modern security framework for secure computation. We demonstrate that, despite the strong impossibility result mentioned above, certain interesting functions can be computed fairly, even when half (or more) of the parties are malicious. We also provide a new notion of partial fairness, demonstrate feasibility of achieving this notion for a large class of functions, and show impossibility for certain functions outside this class. We consider fairness in the presence of rational adversaries, and, finally, we study the difficulty of achieving fairness by exploring how much external help is necessary for providing fair secure computation.
Flatness-Based Tracking of an Electromechanical Variable Valve Timing Actuator With Disturbance Observer Feedforward Compensation

A comprehensive control strategy for an automotive solenoid variable valve timing actuator is presented that addresses the issues of feedback sensors, soft seating or landing control, disturbance rejection and feedforward design. In particular, the motion control of the engine exhaust valve actuator subject to large cycle-to-cycle gas force variations is successfully demonstrated in simulation and on an experimental test-bench. Also provided is a method of characterization and online cycle-to-cycle identification of combustion gas force disturbances. The identified gas forces are used in energy-based feedforward and flatness-based landing algorithms. Simulated and experimental results indicate the proposed control methodology is capable of compensating for the combustion gas force disturbances experienced by exhaust valve solenoid actuators.
AREGU November 46/5

Rinaman, Linda. A functional role for central glucagonlike peptide-1 receptors in lithium chloride-induced anorexia. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46): R1537–R1540, 1999. —The present study sought to determine whether central glucagon-like peptide-1 (GLP-1)receptor signalling contributes to the anorexigenic effects of systemically administered lithium chloride (LiCl). Male Sprague-Dawley rats with chronic intracerebroventricular (ICV) cannulas were acclimated to a feeding schedule that included daily 30-min access to palatable mash. In the first experiment, ICV infusion of a GLP-1-receptor antagonist [exendin-4-(3—39)] significantly attenuated (10 μg dose) or completely blocked (20 μg dose) the inhibition of food intake produced by subsequent ICV infusion of GLP-1-(7—36) amide (5 μg). In the second experiment, rats were infused with 0, 10, or 20 μg of the GLP-1-receptor antagonist ICV, followed by injection of 0.15 M LiCl (50 mg/kg ip) or the same volume of 0.15 M NaCl. The ability of LiCl treatment to suppress food intake was significantly attenuated in rats that were pretreated with the GLP-1-receptor antagonist. These results support the view that central mechanisms underlying LiClinduced anorexia include a prominent role for endogenous GLP-1 neural pathways.