Calculation of the effect of random superfluid density on the temperature dependence of the penetration depth

Microscopic variations in composition or structure can lead to nanoscale inhomogeneity in superconducting properties such as the magnetic penetration depth, but measurements of these properties are usually made on longer length scales. We solve a generalized London equation with a non-uniform penetration depth, lambda(r), obtaining an approximate solution for the disorder-averaged Meissner effect. We find that the effective penetration depth is different from the average penetration depth and is sensitive to the details of the disorder. These results indicate the need for caution when interpreting measurements of the penetration depth and its temperature dependence in systems which may be inhomogeneous

Control of inflorescence architecture in tomato by BTB/POZ transcriptional regulators

Plant productivity depends on inflorescences, flower-bearing shoots that originate from the stem cell populations of shoot meristems. Inflorescence architecture determines flower production, which can vary dramatically both between and within species. In tomato plants, formation of multiflowered inflorescences depends on a precisely timed process of meristem maturation mediated by the transcription factor gene TERMINATING FLOWER (TMF), but the underlying mechanism is unknown. We show that TMF protein acts together with homologs of the Arabidopsis BLADE-ON-PETIOLE (BOP) transcriptional cofactors, defined by the conserved BTB (Broad complex, Tramtrack, and Bric-a-brac)/POZ (POX virus and zinc finger) domain. TMF and three tomato BOPs (SlBOPs) interact with themselves and each other, and TMF recruits SlBOPs to the nucleus, suggesting formation of a transcriptional complex. Like TMF, SlBOP gene expression is highest during vegetative and transitional stages of meristem maturation, and CRISPR/Cas9 elimination of SlBOP function causes pleiotropic defects, most notably simplification of inflorescences into single flowers, resembling tmf mutants. Flowering defects are enhanced in higher-order slbop tmf mutants, suggesting that SlBOPs function with additional factors. In support of this, SlBOPs interact with TMF homologs, mutations in which cause phenotypes like slbop mutants. Our findings reveal a new flowering module defined by SlBOP-TMF family interactions that ensures a progressive meristem maturation to promote inflorescence complexity

Genomic Assessment of Blood-Derived Circulating Tumor DNA in Patients With Colorectal Cancers: Correlation With Tissue Sequencing, Therapeutic Response, and Survival.

PurposeGenomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with colorectal cancers were correlated with clinical outcomes.Patients and methodsNext-generation sequencing of ctDNA (54- to 73-gene panel) was performed in 94 patients with colorectal cancer.ResultsMost patients (96%) had metastatic or recurrent disease at the time of blood draw. The median number of nonsynonymous alterations per patient was three (range, zero to 30). The most frequently aberrant genes were TP53 (52.1% of patients), KRAS (34%), and APC (28.7%). Concordance between tissue and blood next-generation sequencing ranged from 63.2% (APC) to 85.5% (BRAF). Altogether, 74 patients (79%) had one or more nonsynonymous alterations, 69 (73%) had one or more potentially actionable alterations, and 61 (65%) had an alteration actionable by a drug approved by the US Food and Drug Administration (on or off label). Lung metastases correlated with improved survival from diagnosis in univariable analysis. ctDNA of 5% or more from blood tests as well as EGFR and ERBB2 (HER2) nonsynonymous alterations correlated with worse survival (but only ERBB2 remained significant in multivariable analysis). No two patients had identical molecular portfolios. Overall, 65% versus 31% of patients treated with matched (n = 17) versus unmatched therapy (n = 18) after ctDNA testing achieved stable disease for 6 months or more, partial response, or complete response (P = .045); progression-free survival, 6.1 versus 2.3 months (P = .08); and survival not reached versus 9.4 months (P = .146; all by multivariable analysis).ConclusionPatients with colorectal cancer have heterogeneous ctDNA profiles, and most harbor potentially actionable ctDNA alterations. Matched therapy yielded higher rates of stable disease for 6 months or more, partial response, or complete response. ctDNA assessment may have clinical utility and merits further investigation

Limits on Superconductivity-Related Magnetization in Sr2_2RuO4_4 and PrOs4_4Sb12_{12} from Scanning SQUID Microscopy

We present scanning SQUID microscopy data on the superconductors Sr2RuO4 (Tc = 1.5 K) and PrOs$_4$Sb$_{12}$ (Tc = 1.8 K). In both of these materials, superconductivity-related time-reversal symmetry-breaking fields have been observed by muon spin rotation; our aim was to visualize the structure of these fields. However in neither Sr$_2$RuO$_4$ nor PrOs$_4$Sb$_{12}$ do we observe spontaneous superconductivity-related magnetization. In Sr$_2$RuO$_4$, many experimental results have been interpreted on the basis of a $px \pm ipy$ superconducting order parameter. This order parameter is expected to give spontaneous magnetic induction at sample edges and order parameter domain walls. Supposing large domains, our data restrict domain wall and edge fields to no more than ~0.1% and ~0.2% of the expected magnitude, respectively. Alternatively, if the magnetization is of the expected order, the typical domain size is limited to ~30 nm for random domains, or ~500 nm for periodic domains.Comment: 8 pages, 7 figures. Submitted to Phys. Rev.

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study.

BACKGROUND:Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. METHODS:We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design. RESULTS:Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high-level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens. CONCLUSIONS:DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery

The evolution of inflorescence diversity in the nightshades and heterochrony during meristem maturation

One of the most remarkable manifestations of plant evolution is the diversity for floral branching systems. These "inflorescences" arise from stem cell populations in shoot meristems that mature gradually to reproductive states in response to environmental and endogenous signals. The morphology of the shoot meristem maturation process is conserved across distantly related plants, raising the question of how diverse inflorescence architectures arise from seemingly common maturation programs. In tomato and related nightshades (Solanaceae), inflorescences range from solitary flowers to highly branched structures bearing hundreds of flowers. Since reproductive barriers between even closely related Solanaceae have precluded a genetic dissection, we captured and compared meristem maturation transcriptomes from five domesticated and wild species reflecting the evolutionary continuum of inflorescence complexity. We find these divergent species share hundreds of dynamically expressed genes, enriched for transcription factors. Meristem stages are defined by distinct molecular states and point to modified maturation schedules underlying architectural variation. These modified schedules are marked by a peak of transcriptome expression divergence during the reproductive transition, driven by heterochronic shifts of dynamic genes, including transcriptional regulators with known roles in flowering. Thus, evolutionary diversity in Solanaceae inflorescence complexity is determined by subtle modifications of transcriptional programs during a critical transitional window of meristem maturation, which we propose underlies similar cases of plant architectural variation. More broadly, our findings parallel the recently described transcriptome "inverse hourglass" model for animal embryogenesis, suggesting both plant and animal morphological variation is guided by a mid-development period of transcriptome divergence