Miracle-dz/UniFAR-FTUs huggingface dataset:
Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation.

BACKGROUND Adjuvant systemic treatment for patients with isolated locoregional recurrence (ILRR) of breast cancer is based on a single reported randomized trial. The trial, conducted by the Swiss Group for Clinical Cancer Research, compared tamoxifen (TAM) with observation after complete excision of the ILRR and proper radiotherapy. We performed a definitive analysis of treatment outcome at >11 years of follow-up, after the majority of the patients had a subsequent event of interest. Patient and methods One hundred and sixty-seven patients with 'good-risk' characteristics of disease were randomized. 'Good-risk' was defined as estrogen receptor expression in the ILRR, or having a disease-free interval of >12 months and a recurrence consisting of three or less tumor nodules, each </=3 cm in diameter. Seventy-nine percent of the patients were postmenopausal at randomization. RESULTS The median follow-up time of the surviving patients was 11.6 years. The median post ILRR disease-free survival (DFS) was 6.5 years with TAM and 2.7 years with observation (P = 0.053). The difference was mainly due to reduction of further local relapses (P = 0.011). In postmenopausal patients, TAM led to an increase of DFS from 33% to 61% (P = 0.006). In premenopausal women, 5-year DFS was 60%, independent of TAM medication. For the whole study population, the median post-recurrence overall survival (OS) was 11.2 and 11.5 years in the observation and the TAM group, respectively; premenopausal patients experienced a 5-year OS of 90% for observation compared with 67% for TAM (P = 0.175), while the respective figures for postmenopausal patients were both 75%. CONCLUSIONS These definitive results confirmed that TAM significantly improves the post-recurrence DFS of patients after local treatment for ILRR. This beneficial effect does not translate into a detectable OS advantage.
Type I Signal Peptidase and Protein Secretion in Staphylococcus epidermidis

ABSTRACT Bacterial protein secretion is a highly orchestrated process that is essential for infection and virulence. Despite extensive efforts to predict or experimentally detect proteins that are secreted, the characterization of the bacterial secretome has remained challenging. A central event in protein secretion is the type I signal peptidase (SPase)-mediated cleavage of the N-terminal signal peptide that targets a protein for secretion via the general secretory pathway, and the arylomycins are a class of natural products that inhibit SPase, suggesting that they may be useful chemical biology tools for characterizing the secretome. Here, using an arylomycin derivative, along with two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identify 11 proteins whose secretion from stationary-phase Staphylococcus epidermidis is dependent on SPase activity, 9 of which are predicted to be translated with canonical N-terminal signal peptides. In addition, we find that the presence of extracellular domains of lipoteichoic acid synthase (LtaS) and the β-lactam response sensor BlaR1 in the medium is dependent on SPase activity, suggesting that they are cleaved at noncanonical sites within the protein. In all, the data define the proteins whose stationary-phase secretion depends on SPase and also suggest that the arylomycins should be valuable chemical biology tools for the study of protein secretion in a wide variety of different bacteria.
Stationary Phase Mutagenesis in B. subtilis: A Paradigm to Study Genetic Diversity Programs in Cells Under Stress

ABSTRACT One of the experimental platforms to study programs increasing genetic diversity in cells under stressful or nondividing conditions is adaptive mutagenesis, also called stationary phase mutagenesis or stress-induced mutagenesis. In some model systems, there is evidence that mutagenesis occurs in genes that are actively transcribed. Some of those genes may be actively transcribed as a result of environmental stress giving the appearance of directed mutation. That is, cells under conditions of starvation or other stresses accumulate mutations in transcribed genes, including those transcribed because of the selective pressure. An important question concerns how, within the context of stochastic processes, a cell biases mutation to genes under selection pressure? Because the mechanisms underlying DNA transactions in prokaryotic cells are well conserved among the three domains of life, these studies are likely to apply to the examination of genetic programs in eukaryotes. In eukaryotes, increasing genetic diversity in differentiated cells has been implicated in neoplasia and cell aging. Historically, Escherichia coli has been the paradigm used to discern the cellular processes driving the generation of adaptive mutations; however, examining adaptive mutation in Bacillus subtilis has contributed new insights. One noteworthy contribution is that the B. subtilis' ability to accumulate chromosomal mutations under conditions of starvation is influenced by cell differentiation and transcriptional derepression, as well as by proteins homologous to transcription and repair factors. Here we revise and discuss concepts pertaining to genetic programs that increase diversity in B. subtilis cells under nutritional stress.
Noradrenergic inputs from locus coeruleus to posterior ventral tegmental area are essential to support ethanol reinforcement

Although dysregulation of the dopaminergic mesolimbic system is generally considered central to addiction, the involvement of other circuits is increasingly being appreciated. An interaction between locus coeruleus (LC) noradrenergic neurons and the posterior ventral tegmental area (pVTA) dopaminergic system, in the processing of drug‐triggered reward, has been suggested, but not demonstrated in behaving animals. Herein, we try to tease out the precise role of noradrenergic neurons in the LC–VTA circuit in mediating reward and reinforcement behavior associated with ethanol. In the standard two‐lever (active/inactive) operant paradigm, the rats were trained to self‐administer ethanol in pVTA and subjected to pharmacological intervention. Intra‐pVTA administration of phenylephrine (alpha‐1 adrenoceptor agonist) increased ethanol self‐administration, while prazosin and disulfiram (agents that reduce noradrenergic tone) produced opposite effects. While degeneration [N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine hydrochloride, DSP‐4, intraperitoneal route] or silencing (lidocaine or muscimol, both via intra‐LC route) of the LC noradrenergic neurons decreased, phenylephrine via the intra‐LC route reinstated ethanol self‐administration. Furthermore, lidocaine reduced ethanol self‐administration, but the effect was fully attenuated by noradrenaline given directly in the pVTA. This suggests that the feedback signals from LC to pVTA are necessary to sustain the ethanol self‐infusion activity. Ethanol self‐administration significantly increased tyrosine hydroxylase immunoreactivity in pVTA and LC; the response was blocked by DSP‐4 pre‐treatment. While dopamine D1, but not D2, receptors were localized on noradrenergic LC neurons, pre‐treatment with SCH‐23390 (intra‐LC) dampened the lever press activity. We suggest that two‐way communications between VTA and LC regions is essential for ethanol‐triggered reinforcement behavior.
Influence of Serum in Hemodialysis Patients on the Expression of Intestinal and Hepatic Transporters for the Excretion of Pravastatin

It is known that the lipid‐lowering agent pravastatin, which is not metabolized by cytochrome P450, is eliminated as an unchanged drug in bile and urine. It is interesting to note that the non‐renal clearance of pravastatin in end‐stage renal failure patients is decreased compared with that of healthy volunteers. This study investigated the influence of uremic serum and toxins on the transport mechanisms of pravastatin to elucidate the cause of decreased non‐renal clearance in end‐stage renal failure patients. Caco‐2 and Hep3B cells were used as models of intestinal epithelial cells and hepatocytes respectively. Normal and uremic serum were deproteinized by treatment with methanol. 3‐Carboxy‐4‐methyl‐5propyl‐2‐furanpropanoic acid (CMPF), hippuric acid, indole‐3‐acetic acid, 3‐indoxyl sulfate, and p‐cresol were chosen as uremic toxins. Uremic serum‐treated Caco‐2 cells exhibited significantly increased accumulation of pravastatin and significantly decreased expression of MRP2 mRNA compared with normal serum‐treated Caco‐2 cells. In addition, the expression of MRP2 mRNA tended to decrease in cells treated with CMPF, indole‐3‐acetic acid, or 3‐indoxyl sulfate. Uremic serum‐treated Hep3B cells showed a significantly decreased initial uptake rate of pravastatin; furthermore, the expressions of OATP1B1 and OATP2B1 mRNA were decreased compared to normal serum‐treated Hep3B cells. These results suggest that the decrease in the non‐renal clearance of pravastatin in end‐stage renal failure patients is partly induced by the downregulation of intestinal MRP2 and hepatic OATP1B1 and/or OATP2B1 by various uremic toxins in end‐stage renal failure patients.
Dual Aperture Photography: Image and Depth from a Mobile Camera

Conventional cameras capture images with limited depth of field and no depth information. Camera systems have been proposed that enable additional depth information to be captured with the image. These systems reduce the resolution of the captured image or result in reduced sensitivity of the lens. We demonstrate a camera that is able to capture extended depth of field images together with depth information at each single frame while requiring minimal impact on the physical design of the camera or its performance. In this paper we show results with a camera for mobile devices, but this technology (named dual aperture to recall the major change in the camera model) can be applied with even greater effect in larger form factor cameras.
A Clinicopathologic Study of Primary Adenosquamous Carcinoma of the Liver

Background: Adenosquamous carcinoma (ASC) is a rare tumor of the liver, which carries a poor prognosis. In this study, we reviewed reported cases of ASC and examined their clinicopathologic features. Materials and Methods: A computer MEDLINE search found 65 histologically defined primary ASC cases reported in the literature from 1975 to 2003, including our case. Of these, detailed data were obtained for 42 cases, and these were subsequently investigated clinicopathologically. Results: Among the 42 cases, 34 were reported to have died of ASC and 5 cases were alive at the time of the study. The mean survival of these 34 cases was 8.7 months. Multivariate analysis revealed that lymph node metastasis and the elevation of total bilirubin were associated with poor survival after surgery, and lymph node metastasis, intrahepatic metastasis, location of tumor in the right lobe, and the pathologic stage were significant factors for all cases. Conclusion: The current study highlights the prognostic factors of ASC of the liver, showing that the prognosis for patients with ASC is poor.
Global increases in kidney cancer incidence, 1973–1992

Reports of increasing rates for kidney cancers in several count prompted this analysis of global incidence trends for total kidney cancers and by subsite. International incidence data for 5-year periods 1973–1977, 1978–1982, 1983–1987 and 1988–1992 were obtained from volumes IV to VII of Cancer Incidence in Five Continents published by the International Agency for Research on Cancer. The USA data for the same 5-year periods were obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Percentage changes in incidence rates were computed using the relative difference between the time periods 1973–1977 and 1988–1992, and annual percentage changes in incidence rates were computed using log linear regression. In 1988–1992, kidney cancer incidence rates (age-adjusted to the world-standard population) were highest in France (16.1/100 000 man-years and 7.3/100 000 woman-years) and lowest in India (2.0 and 0.9, respectively). Between 1973–1977 and 1988–1992, incidence rates rose among men and women in all regions and ethnic groups, with a few exceptions, mostly in Scandinavian countries. The largest percentage increase for men was in Japan (171%) and for women in Italy (107%). Rates for renal pelvis cancer were less than 1/100 000 person-years in almost all regions in both sexes, and the temporal trends were inconsistent. Incidence trends for renal parenchyma cancer tracked those for total kidney cancers, and appeared to result from increases in the prevalence of risk factors and in use of diagnostic imaging procedures.
Decoupled EKF for simultaneous target model and relative pose estimation using feature points

In this paper, the problem of combined target model and relative pose estimation for position-based visual servoing is addressed. The target object is assumed to be stationary with at least 3 distinguishable feature points. The midpoint triangulation method and a rough estimation method are developed for initial estimation of the target model and relative pose of target in current robot end-effector frame. A novel decoupled extended Kalman Filter (EKF)-based online estimation algorithm is proposed to improve the target model and relative pose estimation simultaneously under continuous robot dynamic motion. This new method is robust to large initial estimation errors and provides consistent and accurate target model estimation for optimal pose estimation as required in position-based visual servoing. Experimental results are given to demonstrate the performance of the proposed method
Effect of treatment with two intravaginal inserts on the uterine and vaginal microflora of early postpartum beef cows.

OBJECTIVE To describe the bacterial species found within the uterus and vagina of early postpartum (10 to 20 d) beef cows treated for 14 d with (i) two intravaginal (CIDR-B) progesterone releasing inserts (C-P4; n=31); (ii) two identical but blank inserts (C-BL; n=15); (iii) untreated controls (CON; n=15). It was hypothesised that due to the locally immunosuppressive effects of progesterone on the uterus, the bacterial microflora of C-P4 would be altered by this treatment in contrast to CON and C-BL. PROCEDURE Cows were enrolled at two intervals 7 d apart. Blood samples were collected at 0, 7 and 14 d after beginning treatments for subsequent progesterone assay. A triple guarded swabbing technique was used to collect bacteriological samples from the uterus of every cow on days 0, 7 and 14 following CIDR insertion. Swabs were also collected from the inserts and vagina of every cow on day 14. Due to the small sample sizes, only descriptive statistics were generated. RESULTS Plasma progesterone levels were maintained at mid-luteal phase concentrations by the intravaginal progesterone releasing inserts (C-P4: 4.2 +/- 0.4 ng/mL at 7 d; 3.6 +/- 0.2 ng/mL at 14 d), although increased progesterone concentrations were found in 4/15 CON and 9/15 C-BL cows on day 14. Bacteria were isolated from 32/61 (52%) of all uterine samples collected at the time of insertion. Uterine and vaginal swabs from CON cows showed a marked reduction in isolates over time such that 14 d after insertion only 1/15 uterine swabs grew bacteria. In contrast, C-BL and C-P4 treated cows failed to show reductions in the number of uterine or vaginal isolates at 14 d after device insertion. Heavy growths of Pseudomonas aeruginosa and Actinomyces pyogenes were found on the intravaginal inserts from C-BL and C-P4 cows. Cows enrolled in the second week of the study that received intravaginal inserts (C-P4 + C-BL) were more likely to have Pseudomonas isolated from the uterus than those enrolled in week 1 (1/18 versus 14/28). CONCLUSIONS The presence of two intravaginal inserts, regardless of hormone content, substantially altered the profile of uterine and vaginal bacteria in early postpartum beef cows. It was suspected that because of the early stage at insert application, the cervix had not involuted sufficiently to provide an adequate microbial barrier to the uterus. Pseudomonas aeruginosa was the predominant species isolated from both uterine and insert cultures after 14 d of treatment but may have been a contaminant, due to the greater proportion of cows infected with it that had been enrolled in the second week of the study.
Navigation Using Sensory Substitution in Real and Virtual Mazes

Under certain specific conditions people who are blind have a perception of space that is equivalent to that of sighted individuals. However, in most cases their spatial perception is impaired. Is this simply due to their current lack of access to visual information or does the lack of visual information throughout development prevent the proper integration of the neural systems underlying spatial cognition? Sensory Substitution devices (SSDs) can transfer visual information via other senses and provide a unique tool to examine this question. We hypothesize that the use of our SSD (The EyeCane: a device that translates distance information into sounds and vibrations) can enable blind people to attain a similar performance level as the sighted in a spatial navigation task. We gave fifty-six participants training with the EyeCane. They navigated in real life-size mazes using the EyeCane SSD and in virtual renditions of the same mazes using a virtual-EyeCane. The participants were divided into four groups according to visual experience: congenitally blind, low vision & late blind, blindfolded sighted and sighted visual controls. We found that with the EyeCane participants made fewer errors in the maze, had fewer collisions, and completed the maze in less time on the last session compared to the first. By the third session, participants improved to the point where individual trials were no longer significantly different from the initial performance of the sighted visual group in terms of errors, time and collision.
Schizophrenia and Substance Abuse: Prevalence Issues

A review of studies of the prevalence of substance abuse among schizophrenics suggest that both demographic and environmental factors are strong determinants of the extent of substance abuse in this population as well as the type of substances used. In a mid-sized Canadian city, a sample of schizophrenic patients referred to a dual diagnoses clinic were administered the Addiction Severity Index. With age and gender included as a factor, no significant differences were found in the choice or length of use of most drugs between diagnostic groups, contrary to some other reports from large urban centres. Compared with a population of a similar age, there were fewer regular and more former drinkers among the schizophrenic patients. The choice of other substances by the sample reflected the pattern of use in the population at large. This approach to prevalence provides a more balanced perspective of the substance abuse by schizophrenics. The major targets for prevention remain the alcohol, caffeine and tobacco consumption.
Reversible patterning of spherical shells through constrained buckling

J. Marthelot,1 P.-T. Brun,2 F. López Jiménez,1 and P. M. Reis1,3,* 1Department of Civil Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA 2Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA 3Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (Received 24 January 2017; published 5 July 2017)
Prevalence of Face Recognition Deficits in Middle Childhood

Approximately 2–2.5% of the adult population is believed to show severe difficulties with face recognition, in the absence of any neurological injury—a condition known as developmental prosopagnosia (DP). However, to date no research has attempted to estimate the prevalence of face recognition deficits in children, possibly because there are very few child-friendly, well-validated tests of face recognition. In the current study, we examined face and object recognition in a group of primary school children (aged 5–11 years), to establish whether our tests were suitable for children and to provide an estimate of face recognition difficulties in children. In Experiment 1 (n = 184), children completed a pre-existing test of child face memory, the Cambridge Face Memory Test–Kids (CFMT-K), and a bicycle test with the same format. In Experiment 2 (n = 413), children completed three-alternative forced-choice matching tasks with faces and bicycles. All tests showed good psychometric properties. The face and bicycle tests were well matched for difficulty and showed a similar developmental trajectory. Neither the memory nor the matching tests were suitable to detect impairments in the youngest groups of children, but both tests appear suitable to screen for face recognition problems in middle childhood. In the current sample, 1.2–5.2% of children showed difficulties with face recognition; 1.2–4% showed face-specific difficulties—that is, poor face recognition with typical object recognition abilities. This is somewhat higher than previous adult estimates: It is possible that face matching tests overestimate the prevalence of face recognition difficulties in children; alternatively, some children may “outgrow” face recognition difficulties.
Any domain of attraction for a linear constrained system is a tracking domain of attraction

We face the problem of determining a tracking domain of attraction, say the set of initial states starting from which it is possible to track reference signals in a given class, for discrete-time systems with control and state constraints. We show that the tracking domain of attraction is exactly equal to the domain of attraction, say the set of states which can be brought to the origin by a proper feedback law. For constant reference signals we establish a connection between the convergence speed of the stabilization problem and tracking convergence which turns out to be independent of the reference signal. We also show that the tracking controller can be inferred from the stabilizing (possibly nonlinear) controller associated with the domain of attraction. The full version of this paper (SIAM J. Contr. Optim., Vol.38 (2000)) includes the continuous-time case, proofs and extensions.
Large Signal Excitation Measurement Techniques for RTS Noise in MOSFETs

This paper introduces large signal excitation measurement techniques to analyze random telegraph signal (RTS) noise originating from oxide-traps in MOSFETs. The paper concentrates on the trap-occupancy, which relates directly to the generated noise. The proposed measurement technique makes trap-occupancy observation possible for every bias-situation, including the OFF-state of the transistor