'What is this corpus about?': Using topic modelling to explore a specialised corpus

This paper introduces topic modelling, a machine learning technique that automatically identifies 'topics' in a given corpus. The paper illustrates its use in the exploration of a corpus of academic English. It first offers the intuitive explanation of the underlying mechanism of topic modelling and describes the procedure for building a model, including the decisions involved in the model-building process. The paper then explores the model. A topic in topic models is characterised by a set of co-occurring words, and we will demonstrate that such topics bring us rich insights into the nature of a corpus. As exemplary tasks, this paper identifies the prominent topics in different parts of papers, investigates the chronological change of a journal, and reveals different types of papers in the journal. The paper further compares topic modelling to two more traditional techniques in corpus linguistics, semantic annotation and keywords analysis, and highlights the strengths of topic modelling.We believe that topic modelling is particularly useful in the initial exploration of a corpus

Parabolic stable surfaces with constant mean curvature

We prove that if u is a bounded smooth function in the kernel of a nonnegative Schrodinger operator $-L=-(\Delta +q)$ on a parabolic Riemannian manifold M, then u is either identically zero or it has no zeros on M, and the linear space of such functions is 1-dimensional. We obtain consequences for orientable, complete stable surfaces with constant mean curvature $H\in\mathbb{R}$ in homogeneous spaces $\mathbb{E}(\kappa,\tau)$ with four dimensional isometry group. For instance, if M is an orientable, parabolic, complete immersed surface with constant mean curvature H in $\mathbb{H}^2\times\mathbb{R}$, then $|H|\leq 1/2$ and if equality holds, then M is either an entire graph or a vertical horocylinder.Comment: 15 pages, 1 figure. Minor changes have been incorporated (exchange finite capacity by parabolicity, and simplify the proof of Theorem 1)

Radio Astronomy

Contains research objectives, summary of research and reports on eleven research projects.National Aeronautics and Space Administration (Grant NGL 22-009-016)National Science Foundation (Grant GP-14854)Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E)National Science Foundation (Grant GP-13056)Sloan Fund for Basic Research (M. I. T. Grant 312

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Index estimates for free boundary minimal hypersurfaces

We show that the Morse index of a properly embedded free boundary minimal hypersurface in a strictly mean convex domain of the Euclidean space grows linearly with the dimension of its first relative homology group (which is at least as big as the number of its boundary components, minus one). In ambient dimension three, this implies a lower bound for the index of a free boundary minimal surface which is linear both with respect to the genus and the number of boundary components. Thereby, the compactness theorem by Fraser and Li implies a strong compactness theorem for the space of free boundary minimal surfaces with uniformly bounded Morse index inside a convex domain. Our estimates also imply that the examples constructed, in the unit ball, by Fraser–Schoen and Folha–Pacard–Zolotareva have arbitrarily large index. Extensions of our results to more general settings (including various classes of positively curved Riemannian manifolds and other convexity assumptions) are discussed

Targeted NGS gene panel identifies mutations in RSPH1 causing primary ciliary dyskinesia and a common mechanism for ciliary central pair agenesis due to radial spoke defects.

Primary ciliary dyskinesia (PCD) is an inherited chronic respiratory obstructive disease with randomized body laterality and infertility, resulting from cilia and sperm dysmotility. PCD is characterized by clinical variability and extensive genetic heterogeneity, associated with different cilia ultrastructural defects and mutations identified in >20 genes. Next generation sequencing (NGS) technologies therefore present a promising approach for genetic diagnosis which is not yet in routine use. We developed a targeted panel-based NGS pipeline to identify mutations by sequencing of selected candidate genes in 70 genetically undefined PCD patients. This detected loss-of-function RSPH1 mutations in four individuals with isolated central pair (CP) agenesis and normal body laterality, from two unrelated families. Ultrastructural analysis in RSPH1-mutated cilia revealed transposition of peripheral outer microtubules into the 'empty' CP space, accompanied by a distinctive intermittent loss of the central pair microtubules. We find that mutations in RSPH1, RSPH4A and RSPH9, which all encode homologs of components of the 'head' structure of ciliary radial spoke complexes identified in Chlamydomonas, cause clinical phenotypes that appear to be indistinguishable except at the gene level. By high-resolution immunofluorescence we identified a loss of RSPH4A and RSPH9 along with RSPH1 from RSPH1-mutated cilia, suggesting RSPH1 mutations may result in loss of the entire spoke head structure. CP loss is seen in up to 28% of PCD cases, in whom laterality determination specified by CP-less embryonic node cilia remains undisturbed. We propose this defect could arise from instability or agenesis of the ciliary central microtubules due to loss of their normal radial spoke head tethering

A multicomponent intervention for the management of chronic pain in older adults: study protocol for a randomized controlled trial

Background: Studies have shown that physical interventions and psychological methods based on the cognitive behavioral approach are efficacious in alleviating pain and that combining both tends to yield more benefits than either intervention alone. In view of the aging population with chronic pain and the lack of evidence-based pain management programs locally, we developed a multicomponent intervention incorporating physical exercise and cognitive behavioral techniques and examined its long-term effects against treatment as usual (i.e., pain education) in older adults with chronic musculoskeletal pain in Hong Kong. Methods/design: We are conducting a double-blind, cluster-randomized controlled trial. A sample of 160 participants aged ≥ 60 years will be recruited from social centers or outpatient clinics and will be randomized on the basis of center/clinic to either the multicomponent intervention or the pain education program. Both interventions consist of ten weekly sessions of 90 minutes each. The primary outcome is pain intensity, and the secondary outcomes include pain interference, pain persistence, pain self-efficacy, pain coping, pain catastrophizing cognitions, health-related quality of life, depressive symptoms, and hip and knee muscle strength. All outcome measures will be collected at baseline, postintervention, and at 3 and 6 months follow-up. Intention-to-treat analysis will be performed using mixed-effects regression to see whether the multicomponent intervention alleviates pain intensity and associated outcomes over and above the effects of pain education (i.e., a treatment × time intervention effect). Discussion: Because the activities included in the multicomponent intervention were carefully selected for ready implementation by allied health professionals in general, the results of this study, if positive, will make available an efficacious, nonpharmacological pain management program that can be widely adopted in clinical and social service settings and will hence improve older people’s access to pain management services

Effects of episodic future thinking and self-projection on children’s prospective memory performance

The present study is the first to investigate the benefits of episodic future thinking (EFT) at encoding on prospective memory (PM) in preschool (age: M = 66.34 months, SD = 3.28)and primary school children (age: M = 88.36 months, SD = 3.12). A second aim was to examine if self-projection influences the possible effects of EFT instructions. PM was assessed using a standard PM paradigm in children with a picture-naming task as the ongoing activity in which the PM task was embedded. Further, two first- and two second-order ToM tasks were administered as indicator of children’s self-projection abilities. Forty-one preschoolers and 39 school-aged children were recruited. Half of the participants in each age group were instructed to use EFT as a strategy to encode the PM task, while the others received standard PM instructions. Results revealed a significant age effect, with school-aged children significantly outperforming preschoolers and a significant effect of encoding condition with overall better performance when receiving EFT instructions compared to the standard encoding condition. Even though the interaction between age group and encoding condition was not significant, planned comparisons revealed first evidence that compared to the younger age group, older children’s PM benefited more from EFT instructions during intention encoding. Moreover, results showed that although self-projection had a significant impact on PM performance, it did not influence the effects of EFT instructions. Overall, results indicate that children can use EFT encoding strategies to improve their PM performance once EFT abilities are sufficiently developed. Further, they provide first evidence that in addition to executive functions, which have already been shown to influence the development of PM across childhood, self-projection seems to be another key mechanism underlying this development

Induction of epigenetic variation in Arabidopsis by over-expression of DNA METHYLTRANSFERASE1 (MET1)

Epigenetic marks such as DNA methylation and histone modification can vary among plant accessions creating epi-alleles with different levels of expression competence. Mutations in epigenetic pathway functions are powerful tools to induce epigenetic variation. As an alternative approach, we investigated the potential of over-expressing an epigenetic function, using DNA METHYLTRANSFERASE1 (MET1) for proof-of-concept. In Arabidopsis thaliana, MET1 controls maintenance of cytosine methylation at symmetrical CG positions. At some loci, which contain dense DNA methylation in CG- and non-CG context, loss of MET1 causes joint loss of all cytosines methylation marks. We find that over-expression of both catalytically active and inactive versions of MET1 stochastically generates new epi-alleles at loci encoding transposable elements, non-coding RNAs and proteins, which results for most loci in an increase in expression. Individual transformants share some common phenotypes and genes with altered gene expression. Altered expression states can be transmitted to the next generation, which does not require the continuous presence of the MET1 transgene. Long-term stability and epigenetic features differ for individual loci. Our data show that over-expression of MET1, and potentially of other genes encoding epigenetic factors, offers an alternative strategy to identify epigenetic target genes and to create novel epi-alleles