A ferromagnet with a glass transition

We introduce a finite-connectivity ferromagnetic model with a three-spin interaction which has a crystalline (ferromagnetic) phase as well as a glass phase. The model is not frustrated, it has a ferromagnetic equilibrium phase at low temperature which is not reached dynamically in a quench from the high-temperature phase. Instead it shows a glass transition which can be studied in detail by a one step replica-symmetry broken calculation. This spin model exhibits the main properties of the structural glass transition at a solvable mean-field level.Comment: 7 pages, 2 figures, uses epl.cls (included

Almost clean rings and arithmetical rings

It is shown that a commutative B\'ezout ring $R$ with compact minimal prime spectrum is an elementary divisor ring if and only if so is $R/L$ for each minimal prime ideal $L$. This result is obtained by using the quotient space $\mathrm{pSpec} R$ of the prime spectrum of the ring $R$ modulo the equivalence generated by the inclusion. When every prime ideal contains only one minimal prime, for instance if $R$ is arithmetical, $\mathrm{pSpec} R$ is Hausdorff and there is a bijection between this quotient space and the minimal prime spectrum $\mathrm{Min} R$, which is a homeomorphism if and only if $\mathrm{Min} R$ is compact. If $x$ is a closed point of $\mathrm{pSpec} R$, there is a pure ideal $A(x)$ such that $x=V(A(x))$. If $R$ is almost clean, i.e. each element is the sum of a regular element with an idempotent, it is shown that $\mathrm{pSpec} R$ is totally disconnected and, $\forall x\in\mathrm{pSpec} R$, $R/A(x)$ is almost clean; the converse holds if every principal ideal is finitely presented. Some questions posed by Facchini and Faith at the second International Fez Conference on Commutative Ring Theory in 1995, are also investigated. If $R$ is a commutative ring for which the ring $Q(R/A)$ of quotients of $R/A$ is an IF-ring for each proper ideal $A$, it is proved that $R_P$ is a strongly discrete valuation ring for each maximal ideal $P$ and $R/A$ is semicoherent for each proper ideal $A$

Multiple-Surrogate Approach to Helicopter Rotor Blade Vibration Reduction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77383/1/AIAA-40291-933.pd

Higher algebraic KK-groups and D\mathcal D-split sequences

In this paper, we use $\mathcal D$-split sequences and derived equivalences to provide formulas for calculation of higher algebraic $K$-groups (or mod-$p$ $K$-groups) of certain matrix subrings which cover tiled orders, rings related to chains of Glaz-Vasconcelos ideals, and some other classes of rings. In our results, we do not assume any homological requirements on rings and ideals under investigation, and therefore extend sharply many existing results of this type in the algebraic $K$-theory literature to a more general context.Comment: 20 page

Nonparametric methods for analyzing replication origins in genomewide data

Due to the advent of high-throughput genomic technology, it has become possible to monitor cellular activities on a genomewide basis. With these new methods, scientists can begin to address important biological questions. One such question involves the identification of replication origins, which are regions in the chromosomes where DNA replication is initiated. One hypothesis is that their locations are nonrandom throughout the genome. In this article, we analyze data from a recent yeast study in which candidate replication origins were profiled using cDNA microarrays to test this hypothesis. We find no evidence for such clustering.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47937/1/10142_2004_Article_122.pd

Stationary relativistic jets

In this paper we describe a simple numerical approach which allows to study the structure of steady-state axisymmetric relativistic jets using one-dimensional time-dependent simulations. It is based on the fact that for narrow jets with vz≈cvz≈c the steady-state equations of relativistic magnetohydrodynamics can be accurately approximated by the one-dimensional time-dependent equations after the substitution z=ctz=ct. Since only the time-dependent codes are now publicly available this is a valuable and efficient alternative to the development of a high-specialised code for the time-independent equations. The approach is also much cheaper and more robust compared to the relaxation method. We tested this technique against numerical and analytical solutions found in literature as well as solutions we obtained using the relaxation method and found it sufficiently accurate. In the process, we discovered the reason for the failure of the self-similar analytical model of the jet reconfinement in relatively flat atmospheres and elucidated the nature of radial oscillations of steady-state jets

A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45)

PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA–MONO comparison of rucaparib versus placebo. METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD

Aspects of coverage in medical DNA sequencing

<p>Abstract</p> <p>Background</p> <p>DNA sequencing is now emerging as an important component in biomedical studies of diseases like cancer. Short-read, highly parallel sequencing instruments are expected to be used heavily for such projects, but many design specifications have yet to be conclusively established. Perhaps the most fundamental of these is the redundancy required to detect sequence variations, which bears directly upon genomic coverage and the consequent resolving power for discerning somatic mutations.</p> <p>Results</p> <p>We address the medical sequencing coverage problem via an extension of the standard mathematical theory of haploid coverage. The expected diploid multi-fold coverage, as well as its generalization for aneuploidy are derived and these expressions can be readily evaluated for any project. The resulting theory is used as a scaling law to calibrate performance to that of standard BAC sequencing at 8× to 10× redundancy, i.e. for expected coverages that exceed 99% of the unique sequence. A differential strategy is formalized for tumor/normal studies wherein tumor samples are sequenced more deeply than normal ones. In particular, both tumor alleles should be detected at least twice, while both normal alleles are detected at least once. Our theory predicts these requirements can be met for tumor and normal redundancies of approximately 26× and 21×, respectively. We explain why these values do not differ by a factor of 2, as might intuitively be expected. Future technology developments should prompt even deeper sequencing of tumors, but the 21× value for normal samples is essentially a constant.</p> <p>Conclusion</p> <p>Given the assumptions of standard coverage theory, our model gives pragmatic estimates for required redundancy. The differential strategy should be an efficient means of identifying potential somatic mutations for further study.</p

A Latent Variable Partial Least Squares Path Modeling Approach to Regional Association and Polygenic Effect with Applications to a Human Obesity Study

Genetic association studies are now routinely used to identify single nucleotide polymorphisms (SNPs) linked with human diseases or traits through single SNP-single trait tests. Here we introduced partial least squares path modeling (PLSPM) for association between single or multiple SNPs and a latent trait that can involve single or multiple correlated measurement(s). Furthermore, the framework naturally provides estimators of polygenic effect by appropriately weighting trait-attributing alleles. We conducted computer simulations to assess the performance via multiple SNPs and human obesity-related traits as measured by body mass index (BMI), waist and hip circumferences. Our results showed that the associate statistics had type I error rates close to nominal level and were powerful for a range of effect and sample sizes. When applied to 12 candidate regions in data (N = 2,417) from the European Prospective Investigation of Cancer (EPIC)-Norfolk study, a region in FTO was found to have stronger association (rs7204609∼rs9939881 at the first intron P = 4.29×10−7) than single SNP analysis (all with P>10−4) and a latent quantitative phenotype was obtained using a subset sample of EPIC-Norfolk (N = 12,559). We believe our method is appropriate for assessment of regional association and polygenic effect on a single or multiple traits

Statistical method on nonrandom clustering with application to somatic mutations in cancer

<p>Abstract</p> <p>Background</p> <p>Human cancer is caused by the accumulation of tumor-specific mutations in oncogenes and tumor suppressors that confer a selective growth advantage to cells. As a consequence of genomic instability and high levels of proliferation, many passenger mutations that do not contribute to the cancer phenotype arise alongside mutations that drive oncogenesis. While several approaches have been developed to separate driver mutations from passengers, few approaches can specifically identify activating driver mutations in oncogenes, which are more amenable for pharmacological intervention.</p> <p>Results</p> <p>We propose a new statistical method for detecting activating mutations in cancer by identifying nonrandom clusters of amino acid mutations in protein sequences. A probability model is derived using order statistics assuming that the location of amino acid mutations on a protein follows a uniform distribution. Our statistical measure is the differences between pair-wise order statistics, which is equivalent to the size of an amino acid mutation cluster, and the probabilities are derived from exact and approximate distributions of the statistical measure. Using data in the Catalog of Somatic Mutations in Cancer (COSMIC) database, we have demonstrated that our method detects well-known clusters of activating mutations in KRAS, BRAF, PI3K, and <it>β</it>-catenin. The method can also identify new cancer targets as well as gain-of-function mutations in tumor suppressors.</p> <p>Conclusions</p> <p>Our proposed method is useful to discover activating driver mutations in cancer by identifying nonrandom clusters of somatic amino acid mutations in protein sequences.</p