Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in p53 are frequent in the preneoplastic stage of mouse mammary tumor development.

Preneoplastic lesions in the mammary gland represent a population of cells at increased risk of progression to tumors. Because p53 is the most commonly mutated gene in human breast cancer, we sought to determine whether mutations in p53 were present in preneoplastic lesions or were acquired during progression to overt tumors. In the mouse mammary gland, hyperplastic alveolar nodules (HAN) are the most common preneoplastic lesion. Analysis of the TM series of transplantable murine HAN outgrowths and tumors allowed the status of p53 to be determined at distinct stages of mammary tumorigenesis. Alterations in the p53 gene or in the pattern of p53 protein expression were observed in all five HAN outgrowth lines examined. Altered expression of p53 protein was detected in 3 of 5 TM HAN outgrowth lines as determined by immunohistochemistry. Overexpression of nuclear p53 was detected in only a fraction of the cells (10-50%) in TM3 and TM4 HAN outgrowths, whereas in tumors that arose from TM4 HAN outgrowths, the proportion of cells overexpressing p53 protein approached approximately 100%. Despite overexpression of p53 in TM3 HAN outgrowths, no tumors have developed in this line. The TM9 outgrowth line exhibited a different pattern of p53 expression by immunohistochemistry: p53 protein was overexpressed in the cytoplasm of virtually all cells in the HAN outgrowths but was localized to the nuclei of TM9 tumor cells. Direct sequencing of p53 transcripts from tumors and cell lines revealed various genetic changes: point mutations in exons 4 and 5 (TM2H, nonsense; TM4, missense); a deletion in exon 5 (TM4); and an insertion in exon 7 (TM3). Although p53 protein was overexpressed in TM9 tumors, it was shown to be wild-type both by immunoprecipitation and direct sequencing of the entire coding region of the cDNA. TM4 cells were homogeneous with respect to mutant p53 genotype and uniformly expressed p53 by immunohistochemical staining in vitro, but transplantation of TM4 cells to fat pads of BALB/c hosts resulted in HAN outgrowths in situ in which < 50% of the cells expressed the mutant p53 at detectable levels. In summary, mutation of the p53 gene and overexpression of p53 protein can occur in preneoplastic mammary epithelial cells, and those mutations are maintained in tumors that arise from the HAN. Conversely, expression of mutant p53 was decreased when cells were grown in situ, implicating the presence of cellular factors that can suppress p53 expression in vivo. These observations demonstrate that the p53 pathway may be a common target for mutation in murine mammary tumorigenesis. (ABSTRACT TRUNCATED AT 400 WORDS)
Addressing the Rare Word Problem in Neural Machine Translation

Neural Machine Translation (NMT) is a new approach to machine translation that has shown promising results that are comparable to traditional approaches. A significant weakness in conventional NMT systems is their inability to correctly translate very rare words: end-to-end NMTs tend to have relatively small vocabularies with a single unk symbol that represents every possible out-of-vocabulary (OOV) word. In this paper, we propose and implement an effective technique to address this problem. We train an NMT system on data that is augmented by the output of a word alignment algorithm, allowing the NMT system to emit, for each OOV word in the target sentence, the position of its corresponding word in the source sentence. This information is later utilized in a post-processing step that translates every OOV word using a dictionary. Our experiments on the WMT’14 English to French translation task show that this method provides a substantial improvement of up to 2.8 BLEU points over an equivalent NMT system that does not use this technique. With 37.5 BLEU points, our NMT system is the first to surpass the best result achieved on a WMT’14 contest task.
Passive nonlinear dendritic interactions as a general computational resource in functional spiking neural networks

Nonlinear interactions in the dendritic tree play a key role in neural computation. Nevertheless, modeling frameworks aimed at the construction of large-scale, functional spiking neural networks tend to assume linear, current-based superposition of post-synaptic currents. We extend the theory underlying the Neural Engineering Framework to systematically exploit nonlinear interactions between the local membrane potential and conductance-based synaptic channels as a computational resource. In particular, we demonstrate that even a single passive distal dendritic compartment with AMPA and GABA-A synapses connected to a leaky integrate-and-fire neuron supports the computation of a wide variety of multivariate, bandlimited functions, including the Euclidean norm, controlled shunting, and non-negative multiplication. Our results demonstrate that, for certain operations, the accuracy of dendritic computation is on a par with or even surpasses the accuracy of an additional layer of neurons in the network. These findings allow modelers to construct large-scale models of neurobiological systems that closer approximate network topologies and computational resources available in biology. Our results may inform neuromorphic hardware design and could lead to a better utilization of resources on existing neuromorphic hardware platforms.
[11C]Raclopride binding in the striatum of minimally restrained and free‐walking awake mice in a positron emission tomography study

Anesthesia and restraint stress have profound impacts on brain functions, including neural activity and cerebrovascular function, possibly influencing functional and neurochemical positron emission tomography (PET) imaging data. For circumventing this effect, we developed an experimental system enabling PET imaging of free‐walking awake mice with minimal restraints by fixing the head to a holder. The applicability of this system was investigated by performing PET imaging of D2 dopamine receptors with [11C]raclopride under the following three different conditions: (1) free‐walking awake state; (2) 1.5% isoflurane anesthesia; and (3) whole‐body restraint without anesthesia. [11C]raclopride binding potential (BPND) values under isoflurane anesthesia and restrained awake state were significantly lower than under free‐walking awake state (P < 0.01). Heart rates in restrained awake mice were significantly higher than those in free‐walking awake mice (P < 0.01), suggesting that free‐walking awake state minimized restraint stress during the PET scan. [11C] raclopride‐PET with methamphetamine (METH) injection was also performed in awake and anesthetized mice. METH‐induced reduction of [11C]raclopride BPND in anesthetized mice showed a trend to be less than that in free‐walking awake mice, implying that pharmacological modulation of dopaminergic transmissions could be sensitively captured by PET imaging of free‐walking awake mice. We concluded that our system is of utility as an in vivo assaying platform for studies of brain functions and neurotransmission elements in small animals, such as those modeling neuropsychiatric disorders. Synapse 69:600–606, 2015. © 2015 Wiley Periodicals, Inc.
Phylogeography, Salinity Adaptations and Metabolic Potential of the Candidate Division KB1 Bacteria Based on a Partial Single Cell Genome

Deep-sea hypersaline anoxic basins and other hypersaline environments contain abundant and diverse microbial life that has adapted to these extreme conditions. The bacterial Candidate Division KB1 represents one of several uncultured groups that have been consistently observed in hypersaline microbial diversity studies. Here we report the phylogeography of KB1, its phylogenetic relationships to Candidate Division OP1 Bacteria, and its potential metabolic and osmotic stress adaptations based on a partial single cell amplified genome of KB1 from Orca Basin, the largest hypersaline seafloor brine basin in the Gulf of Mexico. Our results are consistent with the hypothesis – previously developed based on 14C incorporation experiments with mixed-species enrichments from Mediterranean seafloor brines – that KB1 has adapted its proteins to elevated intracellular salinity, but at the same time KB1 apparently imports glycine betaine; this compatible solute is potentially not limited to osmoregulation but could also serve as a carbon and energy source.
Retractability of solutions to the Yang-Baxter equation and p-nilpotency of skew braces

Using Bieberbach groups, we study multipermutation involutive solutions to the Yang–Baxter equation. We use a linear representation of the structure group of an involutive solution to study the unique product property in such groups. An algorithm to find subgroups of a Bieberbach group isomorphic to the Promislow subgroup is introduced and then used in the case of structure group of involutive solutions. To extend the results related to retractability to non-involutive solutions, following the ideas of Meng, Ballester-Bolinches and Romero, we develop the theory of right [Formula: see text]-nilpotent skew braces. The theory of left [Formula: see text]-nilpotent skew braces is also developed and used to give a short proof of a theorem of Smoktunowicz in the context of skew braces.
PITAVASTATIN SUPPRESSES FORMATION AND PROGRESSION OF CEREBRAL ANEURYSMS THROUGH INHIBITION OF THE NUCLEAR FACTOR κB PATHWAY

OBJECTIVERecent investigations strongly suggest that the pathophysiology of cerebral aneurysms (CA) is closely associated with chronic inflammation in vascular walls. Nuclear factor κB (NF-κB) has a key role in the formation and progression of CAs. Because statins exert anti-inflammatory effects in various vascular diseases, we investigated the effect of pitavastatin on NF-κB activation and CA formation in experimentally induced CAs in rats. METHODSCAs were induced in Sprague-Dawley rats with or without administration of pitavastatin (4 mg/kg/d orally). Size, change of internal elastic lamina, and media thickness of induced CAs were measured in both groups after aneurysm induction. The effects of pitavastatin on NF-κB activation in aneurysmal walls were examined by immunohistochemistry and gel shift assay. Expression of downstream genes was analyzed by quantitative polymerase chain reaction and immunohistochemistry. To examine whether pitavastatin has a suppressive effect on preexisting CAs, pitavastatin administration started 1 month after aneurysm induction. RESULTSPitavastatin treatment significantly prevented CA progression (P < 0.01) and NF-κB activation in aneurysmal walls. Expression of monocyte chemotactic protein-1, vascular cell adhesion molecule-1, interleukin-1β, inducible nitric oxide synthase, and matrix metalloproteinase-9 in aneurysmal walls was also inhibited by pitavastatin. Pitavastatin treatment led to media thickening in preexisting CAs. CONCLUSIONPitavastatin has a suppressive effect on CA progression through the inhibition of NF-κB activation in aneurysmal walls. Moreover, pitavastatin treatment can cause the regression of degenerative changes in preexisting CA walls. Pitavastatin is a promising candidate for a novel preventive agent against subarachnoid hemorrhage.
Adaptive Regret of Convex and Smooth Functions

We investigate online convex optimization in changing environments, and choose the adaptive regret as the performance measure. The goal is to achieve a small regret over every interval so that the comparator is allowed to change over time. Different from previous works that only utilize the convexity condition, this paper further exploits smoothness to improve the adaptive regret. To this end, we develop novel adaptive algorithms for convex and smooth functions, and establish problem-dependent regret bounds over any interval. Our regret bounds are comparable to existing results in the worst case, and become much tighter when the comparator has a small loss.
Atomic lattice disorder in charge-density-wave phases of exfoliated dichalcogenides (1T-TaS2)

Significance Low-dimensional materials, such as 1T-TaS2, permit unique phases that arise through electronic and structural reshaping known, respectively, as charge-density waves and periodic lattice distortions (PLDs). Determining the atomic structure of PLDs is critical toward understanding the origin of these charge-ordered phases and their effect on electronic properties. Here we reveal the microscopic nature of PLDs at cryogenic and room temperature in thin flakes of 1T-TaS2 using atomic resolution scanning transmission electron microscopy. Real-space characterization of the local PLD structure across the phase diagram will enable harnessing of emergent properties of thin transition-metal dichalcogenides. Charge-density waves (CDWs) and their concomitant periodic lattice distortions (PLDs) govern the electronic properties in several layered transition-metal dichalcogenides. In particular, 1T-TaS2 undergoes a metal-to-insulator phase transition as the PLD becomes commensurate with the crystal lattice. Here we directly image PLDs of the nearly commensurate (NC) and commensurate (C) phases in thin, exfoliated 1T-TaS2 using atomic resolution scanning transmission electron microscopy at room and cryogenic temperature. At low temperatures, we observe commensurate PLD superstructures, suggesting ordering of the CDWs both in- and out-of-plane. In addition, we discover stacking transitions in the atomic lattice that occur via one-bond-length shifts. Interestingly, the NC PLDs exist inside both the stacking domains and their boundaries. Transitions in stacking order are expected to create fractional shifts in the CDW between layers and may be another route to manipulate electronic phases in layered dichalcogenides.
Breakdown of B cell tolerance in a mouse model of systemic lupus erythematosus

Anti-DNA antibodies, specifically those that stain nuclei in a homogenous nuclear (HN) fashion, are diagnostic of systemic lupus erythematosus (SLE) and the MRL-lpr/lpr SLE murine model. We have used a heavy chain transgene that increases the frequency of anti-HN antibodies to address whether their production in SLE is the consequence of a defect in B cell tolerance. Anti-HN B cells were undetectable in nonautoimmune-prone transgenic mice, but in MRL-lpr/lpr transgenic mice their Ig was evident in the sera and they were readily retrievable as hybridomas. We conclude that nonautoimmune animals actively delete anti-HN-specific B cells, and that MRL-lpr/lpr mice are defective in this process possibly because of the lpr defect in the fas gene.
Deep Linguistic Processing for Spoken Dialogue Systems

We describe a framework for deep linguistic processing for natural language understanding in task-oriented spoken dialogue systems. The goal is to create domaingeneral processing techniques that can be shared across all domains and dialogue tasks, combined with domain-specific optimization based on an ontology mapping from the generic LF to the application ontology. This framework has been tested in six domains that involve tasks such as interactive planning, coordination operations, tutoring, and learning.
Variation in personality traits of medical students between schools of medicine

Introduction: While there have been studies exploring the impact of personality on medical student selection and performance there has not been an investigation of the personality of students at different schools. Method: Demographic data and responses to the NEO measure of personality traits were collected from medical students in the first two weeks of their enrolment (2011) in seven medical schools in Australia. Personality traits were analysed by school features, gender and age using logistic regression. Results: Differences were detected between schools in the personality traits of Agreeableness and Conscientiousness. Higher Agreeableness and Conscientiousness were associated with attending an Undergraduate school (OR = 1.07 and 1.03, respectively) and a rural or community focussed school (1.06 and 1.03). Students attending a school that used interviews for selection had higher levels of Agreeableness (1.04) and lower levels of Neuroticism (0.96). Discussion: This is the first study to demonstrate that personality traits differ between students entering different medical schools. While there seems to be logic behind some differences, others are perplexing. Further research should expand on these findings and the implications to schools in regards to attracting students through selection processes, mission statements and their broader social focus.
Recognition and repair of UV lesions in loop structures of duplex DNA by DASH-type cryptochrome

DNA photolyases and cryptochromes (cry) form a family of flavoproteins that use light energy in the blue/UV-A region for the repair of UV-induced DNA lesions or for signaling, respectively. Very recently, it was shown that members of the DASH cryptochrome subclade repair specifically cyclobutane pyrimidine dimers (CPDs) in UV-damaged single-stranded DNA. Here, we report the crystal structure of Arabidopsis cryptochrome 3 with an in-situ-repaired CPD substrate in single-stranded DNA. The structure shows a binding mode similar to that of conventional DNA photolyases. Furthermore, CPD lesions in double-stranded DNA are bound and repaired with similar efficiency as in single-stranded DNA if the CPD lesion is present in a loop structure. Together, these data reveal that DASH cryptochromes catalyze light-driven DNA repair like conventional photolyases but lack an efficient flipping mechanism for interaction with CPD lesions within duplex DNA.
Connections

Core Element Connections Structure Basis in Research Relevant Research Teachers organize active learning and focused assessments within clear structure focused on core curriculum. Five week units Weekly development from introduction (Monday) through assessment (Thursday) and revision/expansion (Friday) Daily Lesson: Focus-Act-Report structure. Effective schools have a balanced curriculum and a systematic internal assessment. Rosenshine and Stevens, 1986. Tyler, 1949. Wiggins and McTighe, 1998. Taylor, Pearson, Clark, and Walpole, 2000. Jacobs, 1989.
Reproducibility and validity of bioimpedance spectroscopy for tracking changes in total body water: implications for repeated measurements.

Bioimpedance spectroscopy (BIS) has been used to track changes in total body water (TBW). Accurate TBW estimations can be influenced by both methodological and biological factors. One methodological variation that contributes to BIS TBW errors is the electrode placement. The purpose of the present study was to compare the reproducibility and validity of fixed-distance electrode placements (5 cm) with the standard single-site electrode placements. Twenty-nine subjects (fifteen men and fourteen women) participated in the reproducibility study, while sixty-nine subjects (thirty-three men and thirty-six women) participated in the validity study. The reproducibility study included two measurements that were taken 24 h apart, while the validity study consisted of a 12-week exercise intervention with measurements taken at weeks 1 and 12. TBW was estimated using BIS and 2H techniques. Reproducibility results indicated that fixed-distance electrodes reduced the day-to-day standard error of the measurement in men (from 1·13 to 0·81 litres) but not in women (0·47 litres). sem values were lower for women than for men, suggesting that BIS TBW estimates are sex dependent. Validity results produced similar accurate findings (mean difference < 0·21 litres). However, fixed-distance electrodes improved delta TBW errors (mean difference improvements>0·04 litres in men, women, and men and women combined). When tracking changes in TBW, fixed-distance electrodes may reduce reproducibility errors and allow for smaller changes to be detected. However, the reduction of reproducibility errors may be greater for men than for women. Therefore, reproducibility calculations should be based on the sex of the sample population.
The discrete potential Boussinesq equation and its multisoliton solutions

An alternate form of discrete potential Boussinesq (BSQ) equation is proposed and its multisoliton solutions are constructed. An ultradiscrete potential BSQ equation is also obtained from the discrete potential BSQ equation using the ultradiscretization technique. The detail of the multisoliton solutions is discussed by using the reduction technique. The lattice potential BSQ equation derived by Nijhoff et al. is also investigated by using the singularity confinement test. The relation between the proposed alternate discrete potential BSQ equation and the lattice potential BSQ equation by Nijhoff et al. is clarified.
Car colour and risk of car crash injury: population based case control study

Globally, road traffic crashes kill about 3000 people a day.1 Identification of modifiable risk factors is an important step in reducing this burden. Previous research suggests that white or light coloured cars are less likely to be involved in a crash, than cars of other colours.2 We investigated the effect of car colour on the risk of a serious injury from a crash, using a population based case control study designed to identify and quantify modifiable risk factors. The Auckland car crash injury study was conducted in the Auckland region of New Zealand between April 1998 and June 1999.3 4 The study population comprised all drivers of cars on public (urban and rural) roads in the region. Cases (n = 571) were all car drivers involved in crashes in which one or more of the …
Allocation of RAM built-in self-repair circuits for SOC dies of 3D ICs

A modern system-on-chip (SOC) may become one of the dies of a three-dimensional (3D) IC using through-silicon via (TSV). Built-in self-repair (BISR) techniques have been widely used to improve the yield of RAMs in a SOC. This paper proposes a memory BISR allocation scheme to allocate shared BISR circuits for RAMs in a SOC die such that the test and repair time and the area of BISR circuits are minimized. To minimize the test and repair time of RAMs in the pre-bond and post-bond test phases, a test scheduling engine is used to determine the pre-bond and post-bond test sequences of RAMs under the corresponding test power constraints. Then, a BISR-circuit minimization algorithm is proposed to reduce the number of required shared BISR circuits for the RAMs under the constraints of pre-bond and post-bond test sequences and distance between the BISR circuit and served RAMs. Simulation results show that in comparison with a dedicated BISR scheme (i.e., each RAM has a self-contained BISR circuit), 35% area reduction can be achieved by the shared BISR scheme planned by the proposed allocation technique under lmm distance constraint, and 500mW and 600mW pre-bond and post-bond test power constraints, respectively.