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With sales of American port growing, domestic wineries are perfecting their grape sources and cellar techniques for making it. We interviewed winemakers across the country to assemble tips on how [...]

An adage that has been a favorite of the California wine industry for a couple of decades now goes something like: 'How do you make a small fortune in the [...]

Is it the parentage of the vines or the environmental conditions of the region that give Sierra Foothills Zinfandels their unique characteristics? This question has been the subject of continuous [...]

Bone-chilling winds spilling down the eastern slope of the Sierra Nevada can drop the winter temperatures in the Carson Valley well below freezing. Summer days of sizzling temperatures and steaming [...]

The linking of diverse protected environments in Peru's arid Nazca region could conserve rare biological species as well as an ancient cultural treasure Sand dunes on top of a mountain? […]

The global implications of a rapidly diminishing Cryosphere urge a human-centered framework to address the sustainability and equity concerns arising from impacts of cryospheric change and economic development. This more inclusive paradigm would enable research and policy approaches premised on causalities, historical injustices, and needs for enhancing the resilience of and for indigenous peoples and smallholders. This framework will need to reconsider what human dimensions can be added to current biophysical monitoring, including evaluations of infrastructure, land and marine resources, institutions, and policies. It should facilitate the sharing of data and lived experiences of people affected by and interacting with social-ecological systems with less sea ice, glaciers, and snow cover.

The manufacturing industry has not stopped at improving its processes to keep up with the changing times. Satisfying the demands of customers and gaining their loyalty has become more important with the ever-increasing competitive market place. New technologies are developed which not only allow reduction of manufacturing costs but also spawn new products that attract new customers and improve company image.

Small-molecule therapeutics demonstrate suboptimal pharmacokinetics and bioavailability due to their hydrophobicity and size. One way to overcome these limitations—and improve their efficacy—is to use “stealth” macromolecular carriers that evade uptake by the reticuloendothelial system. Although unstructured polypeptides are of increasing interest as macromolecular drug carriers, current recombinant polypeptides in the clinical pipeline typically lack stealth properties. We address this challenge by developing new unstructured polypeptides, called zwitterionic polypeptides (ZIPPs), that exhibit “stealth” behavior in vivo. We show that conjugating paclitaxel to a ZIPP imparts amphiphilicity to the polypeptide chain that is sufficient to drive its self-assembly into micelles. This in turn increases the half-life of paclitaxel by 17-fold compared to free paclitaxel, and by 1.6-fold compared to the nonstealth control, i.e., ELP-paclitaxel. Treatment of mice bearing highly aggressive prostate or colon cancer with a single dose of ZIPP-paclitaxel nanoparticles leads to near-complete eradication of the tumor, and these nanoparticles have a wider therapeutic window than Abraxane, an FDA-approved taxane nanoformulation.

Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful1. Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives2. Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7% and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening.

Radiation–induced pulmonary fibrosis (RTPF) is a progressive, serious condition in many subjects treated for thoracic malignancies or after accidental nuclear exposure. No biomarker exists for identifying the irradiated subjects most susceptible to pulmonary fibrosis (PF). Previously, we determined that gastrin-releasing peptide (GRP) was elevated within days after birth in newborns exposed to hyperoxia who later developed chronic lung disease. The goal of the current study was to test whether radiation (RT) exposure triggers GRP release in mice and whether this contributes to RTPF in vivo. We determined urine GRP levels and lung GRP immunostaining in mice 0 to 24 after post-thoracic RT (15 Gy). Urine GRP levels were significantly elevated between 24 hours post-RT; GRP-blocking monoclonal antibody 2A11, given minutes post-RT, abrogated urine GRP levels by 6 to 12 hours and also altered phosphoprotein signaling pathways at 24 hours post-RT. Strong extracellular GRP immunostaining was observed in lung at 6 hours post-RT. Mice given one dose of GRP monoclonal antibody 2A11 24 hours post-RT had significantly reduced myofibroblast accumulation and collagen deposition 15 weeks later, indicating protection against lung fibrosis. Therefore, elevation of urine GRP could be predictive of RTPF development. In addition, transient GRP blockade could mitigate PF in normal lung after therapeutic or accidental RT exposure.

Global warming is forcing many species to shift their distributions upward, causing consequent changes in the compositions of species that occur at specific locations. This prediction remains largely untested for tropical trees. Here we show, using a database of nearly 200 Andean forest plot inventories spread across more than 33.5° latitude (from 26.8° S to 7.1° N) and 3,000-m elevation (from 360 to 3,360 m above sea level), that tropical and subtropical tree communities are experiencing directional shifts in composition towards having greater relative abundances of species from lower, warmer elevations. Although this phenomenon of ‘thermophilization’ is widespread throughout the Andes, the rates of compositional change are not uniform across elevations. The observed heterogeneity in thermophilization rates is probably because of different warming rates and/or the presence of specialized tree communities at ecotones (that is, at the transitions between distinct habitats, such as at the timberline or at the base of the cloud forest). Understanding the factors that determine the directions and rates of compositional changes will enable us to better predict, and potentially mitigate, the effects of climate change on tropical forests.

The article presents information on the U.S. saving and loan league. When the Senate finally got around to passing its version of the 1962 tax bill; no one was surprised at the absence of tile President's proposal for the withholding of taxes on dividend and interest income. The U.S. Savings and Loan League, representing most of the nation's 6,200 savings and loan associations, had conducted such an effective lobby against the proposal that tile majority of the Senate would rather have cast a vote favoring foreign aid to Cuba. In power-conscious Washington, the league's campaign served as clear proof that the savings and loan industry had "arrived." But the campaign may, in the long run, prove to have been too, effective, It incurred public Presidential wrath and it led to renewed interest in the workings of what has been termed the nation's "informal" banking system.

The purpose of this study was to survey the use of musculoskeletal diagnostic ultrasound imaging (MSK-DUSI) at chiropractic educational programs worldwide and to elicit opinions of academic diagnostic imaging staff of its prospective use at their teaching institutions.

I agree with Richard Vedder when he says that the writing and critical thinking skills of seniors are only slightly more advanced than those of freshmen ('The Government Yoke,' April). [...]

In this retrospective reading study, we demonstrated a clear improvement in diagnostic accuracy of two-dimensional (2D) mammography with the use of 2D or synthetic 2D mammography plus digital breast tomosynthesis compared with 2D mammography alone, with a significant reduction (56%) in odds of receiving false-positive results.

Sometimes I wonder if our fearless leaders really believe that it is them that the world keeps asking for? I am sure that any country which asks for our military's [...]

It's time for the TTB to join the 21st Century. Although reincarnated from the Bureau of Alcohol, Tobacco and Firearms under the provision of the Homeland Security Act in 2003, [...]