Impaired nutrient signaling and body weight control in a Na⁺ neutral amino acid cotransporter (Slc6a19)-deficient mouse

Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0) amino acid transporter BᴼAT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Na⁺ -dependent uptake of neutral amino acids into the intestine and renal brush-border membrane vesicles was abolished. No compensatory increase of peptide transport or other neutral amino acid transporters was detected. Mice lacking BᴼAT1 showed a reduced body weight. When adapted to a standard 20% protein diet, BᴼAT1-deficient mice lost body weight rapidly on diets containing 6 or 40% protein. Secretion of insulin in response to food ingestion after fasting was blunted. In the intestine, amino acid signaling to the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the GCN2/ATF4 stress response pathway was activated, indicating amino acid deprivation in epithelial cells. The results demonstrate that epithelial amino acid uptake is essential for optimal growth and body weight regulation.This work was supported by National Health and Medical Research Council Grant 525415, Australian Research Council Grant DP0877897, University of Sydney Bridging Grant RIMS2009-02579), and by an anonymous foundatio

Project Antares: A low cost modular launch vehicle for the future

The single stage to orbit launch vehicle Antares is based upon the revolutionary concept of modularity, enabling the Antares to efficiently launch communications satellites, as well as heavy payloads, into Earth's orbit and beyond. The basic unit of the modular system, a single Antares vehicle, is aimed at launching approximately 10,000 kg into low Earth orbit (LEO). When coupled with a Centaur upper stage it is capable of placing 3500 kg into geostationary orbit. The Antares incorporates a reusable engine, the Dual Mixture Ratio Engine (DMRE), as its propulsive device. This enables Antares to compete and excel in the satellite launch market by dramatically reducing launch costs. Antares' projected launch costs are $1340 per kg to LEO which offers a tremendous savings over launch vehicles available today. Inherent in the design is the capability to attach several of these vehicles together to provide heavy lift capability. Any number of these vehicles, up to seven, can be attached depending on the payload and mission requirements. With a seven vehicle configuration Antares's modular concept provides a heavy lift capability of approximately 70,000 kg to LEO. This expandability allows for a wider range of payload options such as large Earth satellites, Space Station Freedom support, and interplanetary spacecraft, and also offers a significant cost savings over a mixed fleet based on different launch vehicles

Tumour-infiltrating lymphocyte scores effectively stratify outcomes over and above p16 post chemo-radiotherapy in anal cancer

Background: The majority (90%) of anal cancers are human papillomavirus (HPV)-driven, identified using immunochemistry for p16. Compared with HPV? patients, those with HPV+ disease generally show improved survival, although relapse rates around 25% indicate a need for further stratification of this group.Methods: Using two cohorts of anal cancer, previously characterised for p16, we assessed the prognostic value of tumour-infiltrating lymphocytes (TILs).Results: Tumour-infiltrating lymphocyte scores were used to stratify p16+ cases, where tumours with absent/low levels of TIL had a relapse-free rate of 63%, as opposed to 92% with high levels of TIL (log rank P=0.006).Conclusions: Assessment of TIL adds to p16 status in the prognosis of anal cancer following chemo-radiotherapy and provides evidence of the clinical importance of the immune response

Trot So Quick: Addressing Budgetary Changes

This session discussed the planning and implementation of strategies taken by the Dean B. Ellis Library to address a significant budget reduction that went into effect in FY19. Holloway and Bailey covered methods taken to optimize a reduced collection development budget and distribute funds to various subject areas in an equitable and justifiable manner. Presenters reviewed meetings conducted with faculty to clarify the new budget and resource alterations. Examples of data provided to stakeholders was shared. Topics covered include deadlines implemented for resource renewals and requests, methods used to track and disclose information regarding the process, and interactions with vendors during this transition. Presenters shared recommendations and information pertaining to unexpected issues experienced during this process

Improving Student Success: Arkansas State’s Partnership with Credo Reference and Regional High School

Are new students coming to your university ready to succeed or are they being overwhelmed by the college experience? Does faculty complain that they spend more time, with increasing frustration, providing basic research instruction to new students? Is your institution being challenged to increase 1st and 2nd year retention rates? Two librarians from Arkansas State University (A-State) will discuss their innovative collaboration in which A-State and Credo are working together to bring information literacy resources and instruction to local high schools in support of college readiness. This session will cover a number of issues, including how the library engaged and garnered administration support, the challenge in establishing meaningful partnerships with local high schools, and developing and tracking the right metrics to validate progress. Topics of discussion will include ways in which the library can do more to enhance its strategic importance relative to administration goals; an overview of the established goals and how success will be tracked in areas including college preparedness, retention, graduation rates, GPA, and recruiting; and why this matters to the A-State Library

Collection Development and Acquisitions Policies and Procedures: Do They Meet the Needs of Today’s Academic Library Environment?

With recent vast changes in formats, purchase/subscription options, and funding sources, many librarians are wondering if their existing policies, procedures, and processes are meeting their library’s needs in the current environment. The presenters hope to create a survey of current practices in library collection development in order to aid librarians seeking different/improved means of doing these duties. Bailey and Creibaum began by providing information on past and present collection development methods of the Dean B. Ellis Library of Arkansas State University, including a brief overview of their allocation formula which is used to determine distribution of funds to departments. Following that, presenters led a lively discussion of current methods used by the attendees who also provided input as to what they would like to be doing differently in their libraries. Attendees were exposed to a number of ideas for improving collection development and acquisitions policies and procedures in their libraries and hopefully left the session with a greater understanding of the variety of processes available to and in use at academic libraries

Stretching Your Dollars: Saving on Online Content

This session, led by two librarians with decades of combined acquisitions experience, was based on the premise that although quality databases can be expensive and only the most fortunate of libraries have unlimited or even plentiful financial resources, there are ways to save funds on these resources. The presenters shared their knowledge about ways to stretch finite library acquisitions funds. Linda Creibaum and Jeff Bailey emphasized tools and strategies attendees could use to save valuable funds on databases and subscriptions. Discussion topics included consortial and volume discounts, the advantages of taking a trial, the importance of keeping notes and checking invoices, strategies for maximizing funds on renewals, and the fine art of negotiation. There was also an open dialogue about some of the rewards to be gained from working with vendors, including free product time and even access to free products

Quantification of Renal Stone Contrast with Ultrasound in Human Subjects

Purpose: Greater visual contrast between calculi and tissue would improve ultrasound (US) imaging of urolithiasis and potentially expand clinical use. The color Doppler twinkling artifact has been suggested to provide enhanced contrast of stones compared with brightness mode (B-mode) imaging, but results are variable. This work provides the first quantitative measure of stone contrast in humans for B-mode and color Doppler mode, forming the basis to improve US for the detection of stones. Materials and Methods: Using a research ultrasound system, B-mode imaging was tuned for detecting stones by applying a single transmit angle and reduced signal compression. Stone twinkling with color Doppler was tuned by using low-frequency transmit pulses, longer pulse durations, and a high-pulse repetition frequency. Data were captured from 32 subjects, with 297 B-mode and Doppler images analyzed from 21 subjects exhibiting twinkling signals. The signal to clutter ratio (i.e., stone to background tissue) (SCR) was used to compare the contrast of a stone on B-mode with color Doppler, and the contrast between stone twinkling and blood-flow signals within the kidney. Results: The stone was the brightest object in only 54% of B-mode images and 100% of Doppler images containing stone twinkling. On average, stones were isoechoic with the tissue clutter on B-mode (SCR = 0 dB). Stone twinkling averaged 37 times greater contrast than B-mode (16 dB, p < 0.0001) and 3.5 times greater contrast than blood-flow signals (5.5 dB, p = 0.088). Conclusions: This study provides the first quantitative measure of US stone to tissue contrast in humans. Stone twinkling contrast is significantly greater than the contrast of a stone on B-mode. There was also a trend of stone twinkling signals having greater contrast than blood-flow signals in the kidney. Dedicated optimization of B-mode and color Doppler stone imaging could improve US detection of stones

Acquisitions for Newbies

Designed specifically for librarians new to the field of acquisitions, this preconference workshop featured an informal introduction to the basics of acquisitions librarianship from three standpoints: an acquisitions librarian, a library director with a background in acquisitions, and a regional sales manager for a key vendor to libraries for e-content and software as a solution. The session covered a variety of issues related to the acquisition of both monographs and serials, print and e-formats, and database and backfile purchases. Discussions included similarities and differences between acquisitions and collection development (and how they can vary from library to library), ordering considerations, avoiding purchase of duplicate resources, negotiating prices and access options, licensing, selecting vendors and jobbers, what a vendor representative expects from librarians, and various services that a company’s representatives can provide to assist librarians. The presenters discussed various aspects of access versus ownership of e-books and periodicals and the impact of each on space and budgets both current and future, various ways to allocate library acquisitions funds, and suggested the best times in the annual budget cycle for different types of spending decisions. Questions and interactive conversations were a welcome part of this open, relaxed exploration of what it means to be an acquisitions librarian in an ever changing library environment

Subsurface Defects in Silicon Investigated by Modulated Optical Reflectance Measurements

The investigation of defects in silicon by modulated optical reflectance measurements has proven to be a powerful and easy-to-use method of nondestructive materials characterization. This technique has been used to monitor ion implant dose [1] and measure polishing damage [2] in silicon wafers, and to map O2 swirl precipitates in Czochralski-grown silicon [3]. Laser-induced modulated reflectance offers advantages over some related thermal-wave techniques: it is contactless, and because it can be performed at modulation frequencies of several MHz, it offers micron-scale resolution. Its noncontact and nondestructive nature makes this technique attractive for production-line use in the semiconductor industry