Evidence of dispersion and refraction of a spectrally broad gravity wave packet in the mesopause region observed by the Na lidar and Mesospheric Temperature Mapper above Logan, Utah

Gravity wave packets excited by a source of finite duration and size possess a broad frequency and wave number spectrum and thus span a range of temporal and spatial scales. Observing at a single location relatively close to the source, the wave components with higher frequency and larger vertical wavelength dominate at earlier times and at higher altitudes, while the lower frequency components, with shorter vertical wavelength, dominate during the latter part of the propagation. Utilizing observations from the Na lidar at Utah State University and the nearby Mesospheric Temperature Mapper at Bear Lake Observatory (41.9ÁN, 111.4ÁW), we investigate a unique case of vertical dispersion for a spectrally broad gravity wave packet in the mesopause region over Logan, Utah (41.7ÁN, 111.8ÁW), that occurred on 2 September 2011, to study the waves\u27 evolution as it propagates upward. The lidar-observed temperature perturbation was dominated by close to a 1 h modulation at 100 km during the early hours but gradually evolved into a 1.5 h modulation during the second half of the night. The vertical wavelength also decreased simultaneously, while the vertical group and phase velocities of the packet apparently slowed, as it was approaching a critical level during the second half of the night. A two-dimensional numerical model is used to simulate the observed gravity wave processes, finding that the location of the lidar relative to the source can strongly influence which portion of the spectrum can be observed at a particular location relative to a source. © 2015. American Geophysical Union. All Rights Reserved

Constructing ‘exceptionality’: a neglected aspect of NHS rationing

The principle of exceptionality involves assessing whether a patient is sufficiently different from the generality of patients to justify providing a treatment, such as an expensive cancer drug, not approved for routine funding. In England, individual requests for certain high-cost treatments are considered by funding request panels that examine exceptionality alongside treatment efficacy and cost as the main criteria for funding. This was also the case in Wales until September 2017. Our paper draws on audio recordings of panel meetings and interviews in a Welsh Health Board to investigate how exceptionality was constructed in discussions. It focuses on the combination of different decision criteria in meeting talk, particularly regarding the discourses associated with efficacy and exceptionality. Exceptionality is a malleable category that raised questions about the evidence-based nature of panel decision making. For example, the paper discusses the use of subgroup data from trials and the difficulty of deciding how small a subgroup of patients should be before it is deemed exceptional. Determining exceptionality has been a key mechanism for deciding that a minority of NHS patients can still receive high-cost treatments not routinely provided for all. As a neglected rationing mechanism

The Lantern Vol. 27, No. 3, Fall 1960

• Thoughts in DaVinici\u27s Coffeehouse • Kinesiology Class • No One is Named Alistair • The Beat Generation • The Super Highway Blues • Panic and the Mountain Peak • The Lake • Later • Ares • The Light • The Room • Thoughts After Three-Thirty • Critique • There • Organized Religion - Pro • Organized Religion - Con • Longing • Apologies to Francois Villon • The Fortune Teller • At Twilight • The Ledge • Waiting at Evening for the Sky to Fall • In Memory of a Friend • The Gentleman • Consumption • Post-Panegyric • The Everglades • Awareness • The Art of Two-Timing • Meditations of an Egyptologist • Sonnet to Mao Tse-Tung • A Strange Affair • With Us Tonight • The Form in Fronthttps://digitalcommons.ursinus.edu/lantern/1078/thumbnail.jp

Condensin I Recruitment to Base Damage-Enriched DNA Lesions Is Modulated by PARP1

Condensin I is important for chromosome organization and segregation in mitosis. We previously showed that condensin I also interacts with PARP1 in response to DNA damage and plays a role in single-strand break repair. However, whether condensin I physically associates with DNA damage sites and how PARP1 may contribute to this process were unclear. We found that condensin I is preferentially recruited to DNA damage sites enriched for base damage. This process is dictated by PARP1 through its interaction with the chromosome-targeting domain of the hCAP-D2 subunit of condensin I

Interactive seminars or small group tutorials in preclinical medical education: results of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Learning in small group tutorials is appreciated by students and effective in the acquisition of clinical problem-solving skills but poses financial and resource challenges. Interactive seminars, which accommodate large groups, might be an alternative. This study examines the educational effectiveness of small group tutorials and interactive seminars and students' preferences for and satisfaction with these formats.</p> <p>Methods</p> <p>Students in year three of the Leiden undergraduate medical curriculum, who agreed to participate in a randomized controlled trial (RCT, n = 107), were randomly allocated to small group tutorials (n = 53) or interactive seminars (n = 54). Students who did not agree were free to choose either format (n = 105). Educational effectiveness was measured by comparing the participants' results on the end-of-block test. Data on students' reasons and satisfaction were collected by means of questionnaires. Data was analyzed using student unpaired t test or chi-square test where appropriate.</p> <p>Results</p> <p>There were no significant differences between the two educational formats in students' test grades. Retention of knowledge through active participation was the most frequently cited reason for preferring small group tutorials, while a dislike of compulsory course components was mentioned more frequently by students preferring interactive seminars. Small group tutorials led to greater satisfaction.</p> <p>Conclusions</p> <p>We found that small group tutorials leads to greater satisfaction but not to better learning results. Interactive learning in large groups might be might be an effective alternative to small group tutorials in some cases and be offered as an option.</p

mRNA knockdown by single strand RNA is improved by chemical modifications

While RNAi has traditionally relied on RNA duplexes, early evaluation of siRNAs demonstrated activity of the guide strand in the absence of the passenger strand. However, these single strands lacked the activity of duplex RNAs. Here, we report the systematic use of chemical modifications to optimize single-strand RNA (ssRNA)-mediated mRNA knockdown. We identify that 2′F ribose modifications coupled with 5′-end phosphorylation vastly improves ssRNA activity both in vitro and in vivo. The impact of specific chemical modifications on ssRNA activity implies an Ago-mediated mechanism but the hallmark mRNA cleavage sites were not observed which suggests ssRNA may operate through a mechanism beyond conventional Ago2 slicer activity. While currently less potent than duplex siRNAs, with additional chemical optimization and alternative routes of delivery, chemically modified ssRNAs could represent a powerful RNAi platform

Comparative analysis of different laser systems to study cellular responses to DNA damage in mammalian cells

Proper recognition and repair of DNA damage is critical for the cell to protect its genomic integrity. Laser microirradiation ranging in wavelength from ultraviolet A (UVA) to near-infrared (NIR) can be used to induce damage in a defined region in the cell nucleus, representing an innovative technology to effectively analyze the in vivo DNA double-strand break (DSB) damage recognition process in mammalian cells. However, the damage-inducing characteristics of the different laser systems have not been fully investigated. Here we compare the nanosecond nitrogen 337 nm UVA laser with and without bromodeoxyuridine (BrdU), the nanosecond and picosecond 532 nm green second-harmonic Nd:YAG, and the femtosecond NIR 800 nm Ti:sapphire laser with regard to the type(s) of damage and corresponding cellular responses. Crosslinking damage (without significant nucleotide excision repair factor recruitment) and single-strand breaks (with corresponding repair factor recruitment) were common among all three wavelengths. Interestingly, UVA without BrdU uniquely produced base damage and aberrant DSB responses. Furthermore, the total energy required for the threshold H2AX phosphorylation induction was found to vary between the individual laser systems. The results indicate the involvement of different damage mechanisms dictated by wavelength and pulse duration. The advantages and disadvantages of each system are discussed

Identification of Allele-Specific RNAi Effectors Targeting Genetic Forms of Parkinson's Disease

Parkinson's disease (PD) is a progressive neurological disorder affecting an estimated 5–10 million people worldwide. Recent evidence has implicated several genes that directly cause or increase susceptibility to PD. As well as advancing understanding of the genetic aetiology of PD these findings suggest new ways to modify the disease course, in some cases through genetic manipulation. Here we generated a ‘walk-through’ series of RNA Pol III-expressed shRNAs targeting both the α-synuclein A30P and LRRK2 G2019S PD-associated mutations. Allele-specific discrimination of the α-synuclein A30P mutation was achieved with alignments at position 10, 13 and 14 in two model systems, including a heterozygous model mimicking the disease setting, whilst 5′RACE was used to confirm stated alignments. Discrimination of the most common PD-linked LRRK2 G2019S mutation was assessed in hemizygous dual-luciferase assays and showed that alignment of the mutation opposite position 4 of the antisense species produced robust discrimination of alleles at all time points studied. Discrimination at this position was subsequently confirmed using siRNAs, where up to 10-fold discrimination was seen. The results suggest that RNAi-mediated silencing of PD-associated autosomal dominant genes could be a novel therapeutic approach for the treatment of the relevant clinical cases of PD in future

Editing independent effects of ADARs on the miRNA/siRNA pathways

Adenosine deaminases acting on RNA (ADARs) are best known for altering the coding sequences of mRNA through RNA editing, as in the GluR-B Q/R site. ADARs have also been shown to affect RNA interference (RNAi) and microRNA processing by deamination of specific adenosines to inosine. Here, we show that ADAR proteins can affect RNA processing independently of their enzymatic activity. We show that ADAR2 can modulate the processing of mir-376a2 independently of catalytic RNA editing activity. In addition, in a Drosophila assay for RNAi deaminase-inactive ADAR1 inhibits RNAi through the siRNA pathway. These results imply that ADAR1 and ADAR2 have biological functions as RNA-binding proteins that extend beyond editing per se and that even genomically encoded ADARs that are catalytically inactive may have such functions