Therapeutic high affinity T cell receptor targeting a KRAS cancer neoantigen.

Neoantigens derived from somatic mutations are specific to cancer cells and are ideal targets for cancer immunotherapy. KRAS is the most frequently mutated oncogene and drives the pathogenesis of several cancers. Here we show the identification and development of an affinity-enhanced T cell receptor (TCR) that recognizes a peptide derived from the most common KRAS mutant, KRAS, presented in the context of HLA-A*11:01.

A Ten-Year Radiostereometric Analysis of Polyethylene Wear Between Oxidized Zirconium and Cobalt Chrome Articulations in Total Hip Arthroplasty.

Background: Oxidized zirconium (OxZi) femoral heads combine the decreased abrasive properties of ceramics with the toughness of metal alloys to lower wear and increase the durability of total hip arthroplasty. The purpose of this study was to compare the 10-year polyethylene wear rates between OxZi/XLPE and cobalt chrome (CoCr)/XLPE articulations.

Methods: A radiostereometric analysis (RSA) was performed on two cohorts of 23 patients who underwent total hip arthroplasty using either OxZi/XLPE or CoCr/XLPE at a minimum of 10-year follow-up.

Determining whether Public Communications Campaigns Based on the The Social Norms Approach are a Viable COVID-19 Prevention Strategy for College Campuses.

The purpose of this study is to (a) outline the formative steps that universities can follow to determine if a media campaign based on the social norms approach (SNA) is a viable method for increasing COVID-19 prevention behaviors among their students, (b) present formative research data collected at a large public land-grant university in the U.S., and (c) as a test case, apply that data to assess the SNA's viability for promoting COVID-19 prevention behaviors among students at that institution.

The long-term effectiveness of a social norming campaign to reduce high-risk drinking: The Michigan State University experience, 2000-2014.

Evaluate effectiveness of a university-wide social norms marketing campaign to reduce high-risk drinking and its consequences among students at MSU. Campaign messages regarding descriptive and injunctive norms were distributed campus-wide from 2001 to 2014 to correct norm misperceptions. Random samples of students surveyed most semesters to monitor message saturation, dosage, and believability along with drinking attitudes, behaviors and harm related to celebratory events.

A C-terminal cysteine residue is required for peptide-based inhibition of the NGF/TrkA interaction at nM concentrations: implications for peptide-based analgesics.

Inhibition of the NGF/TrkA interaction presents an interesting alternative to the use of non-steroidal anti-inflammatories and/or opioids for the control of inflammatory, chronic and neuropathic pain. Most prominent of the current approaches to this therapy is the antibody Tanezumab, which is a late-stage development humanized monoclonal antibody that targets NGF. We sought to determine whether peptides might similarly inhibit the NGF/TrkA interaction and so serve as future therapeutic leads.

Larval settlement: the role of surface topography for sessile coral reef invertebrates.

For sessile marine invertebrates with complex life cycles, habitat choice is directed by the larval phase. Defining which habitat-linked cues are implicated in sessile invertebrate larval settlement has largely concentrated on chemical cues which are thought to signal optimal habitat. There has been less effort establishing physical settlement cues, including the role of surface microtopography.

The effects of physical and chemical treatments on Na2S produced feather keratin films.

The industrial utilisation of feather keratin as a biopolymer has proven difficult due to the lack of a viable extraction technique and the poor mechanical properties of the regenerated products. Here, pure keratin films were produced from chicken feathers using sodium sulphide as sole extraction reagent in a scheme that allows films to be formed without residual chemicals. In a comparison to other films, those produced using Na2S extraction were found to be superior to other regenerated protein films and were similar to un-oriented commercial polymers.

Micro-fabricated polydimethyl siloxane (PDMS) surfaces regulate the development of marine microbial biofilm communities.

This study explored an antifouling (AF) concept based on deployment of microfabricated polydimethyl siloxane (PDMS) surfaces with 1-10 μm periodicity corrugated topographies in temperate marine waters. The effect of the surfaces on the development of microbial biofilms over 28 days and during different seasons, including both summer and winter, was examined using confocal laser scanning microscopy (CLSM) as well as terminal restriction fragment (T-RF) analysis for phylogenetic fingerprinting. The microscale topography significantly impacted biofilm development by altering the attachment pattern and reducing microcolony formation on the 1, 2 and 4 μm PDMS surfaces.

ProxiMAX randomization: a new technology for non-degenerate saturation mutagenesis of contiguous codons.

Back in 2003, we published 'MAX' randomization, a process of non-degenerate saturation mutagenesis using exactly 20 codons (one for each amino acid) or else any required subset of those 20 codons. 'MAX' randomization saturates codons located in isolated positions within a protein, as might be required in enzyme engineering, or else on one face of an α-helix, as in zinc-finger engineering. Since that time, we have been asked for an equivalent process that can saturate multiple contiguous codons in a non-degenerate manner.

The fouling hydroid Ectopleura larynx: a lack of effect of next generation antifouling technologies.

The hydroid Ectopleura larynx is one of the main fouling organisms on salmon aquaculture cages in Norway; this study investigated novel surface materials and microtopographies to deter its settlement. The settlement preferences of hydroid larvae for 12 materials with wettabilities ranging from hydrophobic (54°) to hydrophilic (112°) were tested in a no-choice bioassay. Although settlement differed between materials, with the highest average settlement on polytetrafluoroethylene (95%) and the lowest on untreated polyurethane (53%), no trend regarding the tested wettabilities could be found and none of the tested materials was able to reduce average settlement below 50%.

Reducing costly falls of total knee replacement patients.

The objective of this study was to determine whether the use of a knee immobilizer brace reduces patient falls associated with the recent use of femoral nerve blocks for pain control after total knee arthroplasty (TKA). The authors conducted a retrospective study to investigate fall rates before and after the introduction of an immobilizer brace. The demographics of patients and total cost of care were examined.

Where to settle--settlement preferences of Mytilus galloprovincialis and choice of habitat at a micro spatial scale.

The global mussel aquaculture industry uses specialised spat catching and nursery culture ropes made of multi-filament synthetic and natural fibres to optimise settlement and retention of mussels for on-growing. However, the settlement ecology and preferences of mussels are poorly understood and only sparse information exists in a commercial context. This study quantified the settlement preferences of pediveligers and plantigrades of Mytilus galloprovincialis on increasingly complex surfaces and settlement locations at a micro spatial scale on and within ropes under commercial hatchery operating conditions using optical microscopy and X-ray micro-computed tomography (µCT).

Environmentally sustainable fibers from regenerated protein.

Concerns for the environment and consumer demand are driving research into environmentally friendly fibers as replacements for part of the 38 million tonnes of synthetic fiber produced annually. While much current research focuses on cellulosic fibers, we highlight that protein fibers regenerated from waste or byproduct sources should also be considered. Feather keratin and wheat gluten may both be suitable.

A mutation affecting ASCORBATE PEROXIDASE 2 gene expression reveals a link between responses to high light and drought tolerance.

Molecular analyses of plants have revealed a number of genes whose expression changes in response to high light (HL), including the H2O2 scavenger, ASCORBATE PEROXIDASE 2 (APX2). We carried out a screen in Arabidopsis thaliana for lesions that alter HL-induced expression of APX2 to identify components in abiotic stress signalling pathways. High light was used as it can be instantaneously applied or removed and accurately measured.

Seed dormancy and ABA metabolism in Arabidopsis and barley: the role of ABA 8'-hydroxylase.

We have investigated the relationship between seed dormancy and abscisic acid (ABA) metabolism in the monocot barley and the dicot Arabidopsis. Whether dormant (D) or non-dormant (ND), dry seed of Arabidopsis and embryos of dry barley grains all had similarly high levels of ABA. ABA levels decreased rapidly upon imbibition, although they fell further in ND than in D.

Taurodontism and learning disabilities in patients with Klinefelter syndrome.

Purpose: The purpose of this descriptive clinical study was to determine the prevalence rates of taurodontism and learning disabilities in a sample of patients with Klinefelter syndrome.

Methods: Questionnaires and dental radiographs of Klinefelter syndrome patients were obtained and analyzed using previously published methods. Prevalence rates were determined for taurodontism and learning disabilities in the sample population and compared to the general population.

An unstable base alters limb and abdominal activation strategies during the flexionrelaxation response.

The flexion-relaxation phenomenon consisting of an erector spinae silent period occurring with trunk flexion can place considerable stress upon tissues. Since individuals often flex their trunks while unstable, the purpose of the study was to examine the effect of an unstable base on the flexion-relaxation response. Fourteen participants flexed at the hips and back while standing on a stable floor or an unstable dyna-disc.

Mechanism of aerobic biological destabilisation of wool scour effluent emulsions.

Wool scouring effluent is a highly polluted industrial wastewater in which the main pollutant, wool wax, is held in a stable oil-in-water emulsion by non-ionic detergent. The use of microbial action to cause emulsion destabilisation has been proposed as a new treatment strategy for this effluent stream. This strategy aims at improving aerobic treatment performance by physically removing the high-COD, slowly bio-degradable wool wax from the system without bio-degradation.

Antisense suppression of a (+)-delta-cadinene synthase gene in cotton prevents the induction of this defense response gene during bacterial blight infection but not its constitutive expression.

In cotton (Gossypium hirsutum) the enzyme (+)-delta-cadinene synthase (CDNS) catalyzes the first committed step in the biosynthesis of cadinane-type sesquiterpenes, such as gossypol, that provide constitutive and inducible protection against pests and diseases. A cotton cDNA clone encoding CDNS (cdn1-C4) was isolated from developing embryos and functionally characterized. Southern analysis showed that CDNS genes belong to a large multigene family, of which five genomic clones were studied, including three pseudogenes and one gene that may represent another subfamily of CDNS.

Plants with increased expression of ent-kaurene oxidase are resistant to chemical inhibitors of this gibberellin biosynthesis enzyme.

The gibberellin (GA) biosynthetic pathway includes the three-step oxidation of ent-kaurene to ent-kaurenoic acid, catalyzed by the enzyme ent-kaurene oxidase (KO). Arabidopsis plants overexpressing the KO cDNA under the control of the cauliflower mosaic virus 35S promoter, with or without a translational fusion to a modified green fluorescent protein (GFP), are very similar to wild-type (WT) plants under normal growth conditions. In contrast, when WT and 35S:KO (or 35S:KO-GFP) seeds, seedlings or pollen tubes are grown in the presence of chemical inhibitors of KO, such as paclobutrazol and uniconazole, plants with increased KO expression are partially resistant to the effects of these inhibitors.

Treatment of biorefractory organic compounds in wool scour effluent by hydroxyl radical oxidation.

Wool scouring effluent that had been treated with chemical flocculation and aerobic biological treatment (Sirolan CFB effluent) was tertiary treated by hydroxyl radical oxidation to remove residual organic compounds. These compounds impart a high chemical oxygen demand of 500-3000 mg/L and dark colour. However, a H2O2/UV process was found to effectively treat the majority of residual compounds, with up to 75% COD, 85% total organic carbon, and 100% removal of colour (T(480 nm)) achieved.

Treatment of strongflow wool scouring effluent by biological emulsion destabilisation.

The stable oil-in-water emulsion contained in wool scouring effluent was destabilised by aerobic biological treatment as the basis of a potential new effluent treatment process. The de-emulsified wool wax, which is recalcitrant to biodegradation, can then be readily removed by centrifugation. In 12-day batch experiments, 97% of wool wax and 87% of COD were removed after gentle centrifuging at 200 x g, compared to only 6% and 8%, respectively, for sterile controls.

The pea gene LH encodes ent-kaurene oxidase.

The pea (Pisum sativum) homolog, PsKO1, of the Arabidopsis GA3 gene was isolated. It codes for a cytochrome P450 from the CYP701A subfamily and has ent-kaurene oxidase (KO) activity, catalyzing the three step oxidation of ent-kaurene to ent-kaurenoic acid in the gibberellin (GA) biosynthetic pathway when expressed in yeast (Saccharomyces cerevisiae). PsKO1 is encoded by the LH gene because in three independent mutant alleles, lh-1, lh-2, and lh-3, PsKO1 has altered sequence, and the lh-1 allele, when expressed in yeast, failed to metabolize ent-kaurene.

New insights into grapevine flowering.

The study of grapevine (Vitis spp.) flowering has unique challenges owing to the unique shoot architecture of the plant and the arrest of the flowering process during winter. The grapevine flowering process: inflorescence number per vine, flower number per inflorescence, fruit set and growth has a major impact on fruitfulness (berries per hectare) and hence yield.

The pea gene NA encodes ent-kaurenoic acid oxidase.

The gibberellin (GA)-deficient dwarf na mutant in pea (Pisum sativum) has severely reduced internode elongation, reduced root growth, and decreased leaflet size. However, the seeds develop normally. Two genes, PsKAO1 and PsKAO2, encoding cytochrome P450 monooxygenases of the subfamily CYP88A were isolated.