Production of Specific Fragments of {varphi}X174 Replicative Form DNA by a Restriction Enzyme from Haemophilus parainfluenzae, Endonuclease HP

A restriction endonuclease from Haemophilus parainfluenzae degrades {varphi}X174 replicative form DNA into eight specific fragments, ranging from 1,700 to 150 base pairs and terminated specifically by deoxycytidylic acid

The 2018-19 Arctic stratospheric polar vortex

The stratospheric polar vortex is a westerly circulation that forms over the winter pole around 10-50 km above the surface, which is known to influence mid-latitude weather patterns. During 2018-19, the Arctic polar vortex demonstrated an unusually large amount of variability, including a strong and persistent sudden stratospheric warming (SSW) event, a strong vortex event, and a dynamic final stratospheric warming (FSW). In this article we discuss the evolution of the vortex, placing it in the context of wider observed climatology, and comment on its apparent impacts on tropospheric weather patterns – notably, the lack of a surface climate response to the SSW of similar magnitude to the February-March 2018 “Beast from the East” cold-wave

A Model for Selecting Technologies in New Product Development

Due to fast changing technologies, shortening product lifecycles, and increased global competition, companies today often need to develop new products continuously and faster. Successful introduction and acceleration of new product development (NPD) is important to obtain competitive advantage for companies. Since technology selection for NPD involves complex decision makings that are critical to the profitability and growth of a company, the selection of the most appropriate technology for a new product requires the use of a robust decision-making framework capable of evaluating several technology candidates based on multiple criteria. This paper presents an integrated model that adopts interpretive structural modeling (ISM) and fuzzy analytic network process (FANP) to evaluate various different available technologies for NPD. The ISM is used to understand the interrelationships among the factors, and the FANP is to facilitate the evaluation process of decision makers under an uncertain environment with interrelated factors. A case study of a flat panel manufacturer is performed to examine the practicality of the proposed model. The results show that the model can be applied for group decision making on the available technology evaluation and selection in new product development

Invasive Haemophilus influenzae Disease in Adults ≥65 Years, United States, 2011.

BackgroundSince the introduction of the Haemophilus influenzae serotype b vaccine, H influenzae epidemiology has shifted. In the United States, the largest burden of disease is now in adults aged ≥65 years. However, few data exist on risk factors for disease severity and outcome in this age group.MethodsA retrospective case-series review of invasive H influenzae infections in patients aged ≥65 years was conducted for hospitalized cases reported to Active Bacterial Core surveillance in 2011.ResultsThere were 299 hospitalized cases included in the analysis. The majority of cases were caused by nontypeable H influenzae, and the overall case fatality ratio (CFR) was 19.5%. Three or more underlying conditions were present in 63% of cases; 94% of cases had at least 1. Patients with chronic heart conditions (congestive heart failure, coronary artery disease, and/or atrial fibrillation) (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.65-6.46), patients from private residences (OR, 8.75; 95% CI, 2.13-35.95), and patients who were not resuscitate status (OR, 2.72; 95% CI, 1.31-5.66) were more likely to be admitted to the intensive care unit (ICU). Intensive care unit admission (OR, 3.75; 95% CI, 1.71-8.22) and do not resuscitate status (OR, 12.94; 95% CI, 4.84-34.55) were significantly associated with death.ConclusionsWithin this age group, burden of disease and CFR both increased significantly as age increased. Using ICU admission as a proxy for disease severity, our findings suggest several conditions increased risk of disease severity and patients with severe disease were more likely to die. Further research is needed to determine the most effective approach to prevent H influenzae disease and mortality in older adults

Constraints on the Heating of High Temperature Active Region Loops: Observations from Hinode and SDO

We present observations of high temperature emission in the core of a solar active region using instruments on Hinode and SDO. These multi-instrument observations allow us to determine the distribution of plasma temperatures and follow the evolution of emission at different temperatures. We find that at the apex of the high temperature loops the emission measure distribution is strongly peaked near 4 MK and falls off sharply at both higher and lower temperatures. Perhaps most significantly, the emission measure at 0.5 MK is reduced by more than two orders of magnitude from the peak at 4 MK. We also find that the temporal evolution in broad-band soft X-ray images is relatively constant over about 6 hours of observing. Observations in the cooler SDO/AIA bandpasses generally do not show cooling loops in the core of the active region, consistent with the steady emission observed at high temperatures. These observations suggest that the high temperature loops observed in the core of an active region are close to equilibrium. We find that it is possible to reproduce the relative intensities of high temperature emission lines with a simple, high-frequency heating scenario where heating events occur on time scales much less than a cooling time. In contrast, low-frequency heating scenarios, which are commonly invoked to describe nanoflare models of coronal heating, do not reproduce the relative intensities of high temperature emission lines and predict low-temperature emission that is approximately an order of magnitude too large. We also present an initial look at images from the SDO/AIA 94 A channel, which is sensitive to Fe XVIII.Comment: Movies are available at http://tcrb.nrl.navy.mil/~hwarren/temp/papers/active_region_core/ Paper has been refereed and revise

Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.

Developmental changes in the temporal and spatial regulation of gene expression drive the emergence of normal mature brain function, while disruptions in these processes underlie many neurodevelopmental abnormalities. To solidify our foundational knowledge of such changes in a primate brain with an extended period of postnatal maturation like in human, we investigated the whole-genome transcriptional profiles of rhesus monkey brains from birth to adulthood. We found that gene expression dynamics are largest from birth through infancy, after which gene expression profiles transition to a relatively stable state by young adulthood. Biological pathway enrichment analysis revealed that genes more highly expressed at birth are associated with cell adhesion and neuron differentiation, while genes more highly expressed in juveniles and adults are associated with cell death. Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex. Using network analysis, we identified 27 co-expression modules containing genes with highly correlated expression patterns that are associated with specific brain regions, ages or both. In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes. This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD

Stereotactic ablative radiotherapy for medically inoperable early stage lung cancer: early outcomes

Objective To evaluate the clinical outcome and safety of stereotactic ablative radiotherapy for medically inoperable stage I non- small-cell lung carcinoma. Design Retrospective case series. Setting Pamela Youde Nethersole Eastern Hospital, Hong Kong. Patients All patients with medically inoperable stage I non-small-cell lung carcinoma receiving stereotactic ablative radiotherapy since its establishment in 2008. Main outcome measures Disease control rate, overall survival, and treatment toxicities. Results Sixteen stage I non-small-cell lung carcinoma patients underwent the procedure from June 2008 to November 2011. The median patient age was 82 years and the majority (81%) had moderate-tosevere co-morbidity based on the Adult Comorbidity Evaluation 27 index. With a median follow-up of 22 months, the 2-year primary tumour control rate, disease-free survival and overall survival rates were 91%, 71% and 87%, respectively. No grade 3 (National Cancer Institute Common Terminology Criteria for Adverse Events) or higher treatment-related complications were reported. Conclusion Stereotactic ablative radiotherapy can achieve a high degree of local control safely in medically inoperable patients with early lung cancer.published_or_final_versio

Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients

Pathway analysis of kidney cancer using proteomics and metabolic profiling

BACKGROUND: Renal cell carcinoma (RCC) is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC). We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. RESULTS: Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values < 2.0 E-05) in glycolysis, propanoate metabolism, pyruvate metabolism, urea cycle and arginine/proline metabolism, as well as in the non-metabolic p53 and FAS pathways. In a pilot study using random urine samples from both ccRCC and control patients, we performed metabolic profiling and found that only sorbitol, a component of an alternative glycolysis pathway, is significantly elevated at 5.4-fold in RCC patients as compared to controls. CONCLUSION: Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy