The \u3cem\u3emir-51\u3c/em\u3e Family of MicroRNAs Functions in Diverse Regulatory Pathways in \u3cem\u3eCaenorhbditis elegans\u3c/em\u3e

The mir-51 family of microRNAs (miRNAs) in C. elegans are part of the deeply conserved miR-99/100 family. While loss of all six family members (mir-51-56) in C. elegans results in embryonic lethality, loss of individual mir-51 family members results in a suppression of retarded developmental timing defects associated with the loss of alg-1. The mechanism of this suppression of developmental timing defects is unknown. To address this, we characterized the function of the mir-51 family in the developmental timing pathway. We performed genetic analysis and determined that mir-51 family members regulate the developmental timing pathway in the L2 stage upstream of hbl-1. Loss of the mir-51 family member, mir-52, suppressed retarded developmental timing defects associated with the loss of let-7 family members and lin-46. Enhancement of precocious defects was observed for mutations in lin-14, hbl-1, and mir-48(ve33), but not later acting developmental timing genes. Interestingly, mir-51 family members showed genetic interactions with additional miRNA-regulated pathways, which are regulated by the let-7 and mir-35 family miRNAs, lsy-6, miR-240/786, and miR-1. Loss of mir-52 likely does not suppress miRNA-regulated pathways through an increase in miRNA biogenesis or miRNA activity. We found no increase in the levels of four mature miRNAs, let-7, miR-58, miR-62 or miR-244, in mir-52 or mir-52/53/54/55/56 mutant worms. In addition, we observed no increase in the activity of ectopic lsy-6 in the repression of a downstream target in uterine cells in worms that lack mir-52. We propose that the mir-51 family functions broadly through the regulation of multiple targets, which have not yet been identified, in diverse regulatory pathways in C. elegans

Ultrastable reference pulser for high-resolution spectrometers

Solid-state double-pulse generator for a high resolution semiconductor detector meets specific requirements for resolution /0.05 percent/, amplitude range /0.1-13 MeV/, and repetition rate /0.1-1000 pulses per second/. A tag pulse is generated in coincidence with each reference pulse

Loss of Individual MicroRNAs Causes Mutant Phenotypes in Sensitized Genetic Backgrounds in \u3cem\u3eC. elegans\u3c/em\u3e

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate the translation and/or stability of their mRNA targets. Previous work showed that for most miRNA genes of C. elegans, single-gene knockouts did not result in detectable mutant phenotypes. This may be due, in part, to functional redundancy between miRNAs. However, in most cases, worms carrying deletions of all members of a miRNA family do not display strong mutant phenotypes. They may function together with unrelated miRNAs or with non-miRNA genes in regulatory networks, possibly to ensure the robustness of developmental mechanisms. To test this, we examined worms lacking individual miRNAs in genetically sensitized backgrounds. These include genetic backgrounds with reduced processing and activity of all miRNAs or with reduced activity of a wide array of regulatory pathways. With these two approaches, we identified mutant phenotypes for 25 out of 31 miRNAs included in this analysis. Our findings describe biological roles for individual miRNAs and suggest that the use of sensitized genetic backgrounds provides an efficient approach for miRNA functional analysis

Design and fabrication of a centrifugally driven microfluidic disk for fully integrated metabolic assays on whole blood

For the first time, we present a novel and fully integrated centrifugal microfluidic “ lab-on-a-disk” for rapid metabolic assays in human whole blood. All essential steps comprising blood sampling, metering, plasma extraction and the final optical detection are conducted within t = 150 s in passive structures integrated on one disposable disk. Our technology features a novel plasma extraction structure (V = 500 nL, CV < 5%) without using any hydrophobic microfluidics where the purified plasma (cRBC< 0.11%) is centrifugally separated and subsequently extracted through a capillarily primed extraction channel into the detection chamber. While this capillary extraction requires precisely defined, narrow micro-structures, the reactive mixing and detection is most efficient within larger cavities. The corresponding manufacturing technique of these macro- and micro structures in the range of 30 µ m to 1000 µ m is also presented for the first time: A novel, cost-efficient hybrid prototyping technique of a multiscale epoxy master for subsequent hot embossing of polymer disks

Job Sharing in Physical Therapy

The profession of physical therapy continues to experience staff shortages in several areas. As these shortages continue, employees and employers will seek to identify alternative work schedules to attempt to meet this demand. Job sharing is one type of alternative where two people share the duties and responsibilities of one full-time position. The purpose of this study was to 1) determine the prevalence of job sharing in physical therapy departments in acute care hospitals and rehab facilities, 2) review the types of schedules utilized by job sharing partners, 3) identify the job title of the shared position, and 4) discuss the perceived advantages/disadvantages to the employee/employer. The sample consisted of 85 randomly selected physical therapy departments in a six-state region. A survey was sent to the director of physical therapy in each facility identified in the sample. Results indicated that job sharing occurred in 23 of the 61 facilities returning the survey (38%) with staff therapist the most common position held by job sharing partners. The average number of FTEs (full-time equivalent) allotted for job sharing positions was 1.5, and the most frequently utilized schedule was 3 days on/2 days off, alternating weeks. Several advantages/disadvantages to the employee/employer are identified. The results of this survey may be beneficial to employees and employers who may be considering job sharing in their facility. It also may offer new ideas to those who currently have this type of arrangement

A Mathematical Model for Estimating Biological Damage Caused by Radiation

We propose a mathematical model for estimating biological damage caused by low-dose irradiation. We understand that the Linear Non Threshold (LNT) hypothesis is realized only in the case of no recovery effects. In order to treat the realistic living objects, our model takes into account various types of recovery as well as proliferation mechanism, which may change the resultant damage, especially for the case of lower dose rate irradiation. It turns out that the lower the radiation dose rate, the safer the irradiated system of living object (which is called symbolically "tissue" hereafter) can have chances to survive, which can reproduce the so-called dose and dose-rate effectiveness factor (DDREF).Comment: 22 pages, 6 Figs, accepted in Journal of the Physical Society of Japa