The CERV protein of Cer1, a C. elegans LTR retrotransposon, is required for nuclear export of viral genomic RNA and can form giant nuclear rods.

Retroviruses and closely related LTR retrotransposons export full-length, unspliced genomic RNA (gRNA) for packaging into virions and to serve as the mRNA encoding GAG and POL polyproteins. Because gRNA often includes splice acceptor and donor sequences used to splice viral mRNAs, retroelements must overcome host mechanisms that retain intron-containing RNAs in the nucleus. Here we examine gRNA expression in Cer1, an LTR retrotransposon in C. elegans which somehow avoids silencing and is highly expressed in germ cells. Newly exported Cer1 gRNA associates rapidly with the Cer1 GAG protein, which has structural similarity with retroviral GAG proteins. gRNA export requires CERV (C. elegans regulator of viral expression), a novel protein encoded by a spliced Cer1 mRNA. CERV phosphorylation at S214 is essential for gRNA export, and phosphorylated CERV colocalizes with nuclear gRNA at presumptive sites of transcription. By electron microscopy, tagged CERV proteins surround clusters of distinct, linear fibrils that likely represent gRNA molecules. Single fibrils, or groups of aligned fibrils, also localize near nuclear pores. During the C. elegans self-fertile period, when hermaphrodites fertilize oocytes with their own sperm, CERV concentrates in two nuclear foci that are coincident with gRNA. However, as hermaphrodites cease self-fertilization, and can only produce cross-progeny, CERV undergoes a remarkable transition to form giant nuclear rods or cylinders that can be up to 5 microns in length. We propose a novel mechanism of rod formation, in which stage-specific changes in the nucleolus induce CERV to localize to the nucleolar periphery in flattened streaks of protein and gRNA; these streaks then roll up into cylinders. The rods are a widespread feature of Cer1 in wild strains of C. elegans, but their function is not known and might be limited to cross-progeny. We speculate that the adaptive strategy Cer1 uses for the identical self-progeny of a host hermaphrodite might differ for heterozygous cross-progeny sired by males. For example, mating introduces male chromosomes which can have different, or no, Cer1 elements.

Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia.

We performed a comprehensive study of the morphological, functional, and genetic features of moonwalker (MWK) mice, a mouse model of spinocerebellar ataxia caused by a gain of function of the TRPC3 channel. These mice show numerous behavioral symptoms including tremor, altered gait, circling behavior, impaired motor coordination, impaired motor learning and decreased limb strength. Cerebellar pathology is characterized by early and almost complete loss of unipolar brush cells as well as slowly progressive, moderate loss of Purkinje cell (PCs). Structural damage also includes loss of synaptic contacts from parallel fibers, swollen ER structures, and degenerating axons. Interestingly, no obvious correlation was observed between PC loss and severity of the symptoms, as the phenotype stabilizes around 2 months of age, while the cerebellar pathology is progressive. This is probably due to the fact that PC function is severely impaired much earlier than the appearance of PC loss. Indeed, PC firing is already impaired in 3 weeks old mice. An interesting feature of the MWK pathology that still remains to be explained consists in a strong lobule selectivity of the PC loss, which is puzzling considering that TRPC is expressed in every PC. Intriguingly, genetic analysis of MWK cerebella shows, among other alterations, changes in the expression of both apoptosis inducing and resistance factors possibly suggesting that damaged PCs initiate specific cellular pathways that protect them from overt cell loss.

Therapeutic Peptides, Proteins and their Nanostructures for Drug Delivery and Precision Medicine.

Peptide and protein nanostructures with tunable structural features, multifunctionality, biocompatibility and biomolecular recognition capacity enable development of efficient targeted drug delivery tools for precision medicine applications. In this review article, we present various techniques employed for the synthesis and self-assembly of peptides and proteins into nanostructures. We discuss design strategies utilized to enhance their stability, drug-loading capacity, and controlled release properties, in addition to the mechanisms by which peptide nanostructures interact with target cells, including receptor-mediated endocytosis and cell-penetrating capabilities. We also explore the potential of peptide and protein nanostructures for precision medicine, focusing on applications in personalized therapies and disease-specific targeting for diagnostics and therapeutics in diseases such as cancer.

Intraoperative challenges and complications of cataract surgery between cataract surgery alone and phacovitrectomy in eyes with diabetic retinopathy: efficacy of illuminated chopper-assisted cataract surgery.

BACKGROUND: To compare the intraoperative challenges, complications, and operation time of illuminated chopper-assisted cataract surgery between cataract surgery only and phacovitrectomy in eyes with diabetic retinopathy. METHODS: One university hospital, retrospective case series. Two hundred ninety-five eyes of 295 consecutive patients with diabetic retinopathy who underwent cataract surgery only or phacovitrectomy were retrospectively reviewed. Intraoperative challenges and complications of cataract surgery were thoroughly analyzed by 3D viewing of digitally recorded videos. The pupil diameter, operation time, and improved efficacy (100/operation time × pupil diameter) were compared between the cataract surgery only and phacovitrectomy groups. RESULTS: Of the 295 eyes, 211 underwent cataract surgery only, and 84 underwent phacovitrectomy. Intraoperative challenges such as small pupil, miosis, or poor red reflex occurred more frequently (46 [21.8%] vs. 28 [33.3%], p = 0.029); pupil diameter was smaller (7.34 ± 0.94 vs. 6.89 ± 0.88 mm, p < 0.001) in the phacovitrectomy group than in the cataract surgery only group; however, rates of posterior capsule rupture and operation time were not different between the two groups (0 [0%] vs. 1 [1.2%], p = 0.285; 16.54 ± 2.65 vs. 16.31 ± 4.30 min, p = 0.434). Improved efficacy was higher in the phacovitrectomy group (0.85 ± 0.18 vs. 0.97 ± 0.28, p = 0.002). CONCLUSIONS: The use of an illuminated chopper is a potential solution for diabetic cataract surgery, particularly in phacovitrectomy, by decreasing the use of supplemental devices, operation time, and posterior capsule rupture. TRIAL REGISTRATION: Retrospectively registered.

Profiles of decent work: General trends and group differences.

Recent trends in the labor market-marked by instability and insecurity-have further ignited a discourse on the significance of decent work in people's lives. Scholars have mostly studied the multidimensional decent work construct using the composite scores of the Decent Work Scale (DWS; Duffy et al., 2017). However, there may be different combinations of decent work beyond the simple continuum of composite scores. Thus, we employed latent profile analysis to identify profiles of decent work using the 5 subscales of the DWS as indicators. As a result, 5 different groups with distinct profiles emerged: (a) average, (b) low health care, (c) indecent work, (d) only health care, and (e) decent work. Subsequent analyses comparing each group on demographics (gender, employment, education), theoretical predictors (economic constraints, marginalization, work volition), and theoretical outcomes (job satisfaction, life satisfaction) revealed notable differences across the 5 groups. Implications, limitations, and future directions of the results are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A cross-cultural comparison of psychology of working theory among U.S. and Korean college students.

The cross-cultural validity of a modified version of psychology of working theory (PWT; Duffy, Blustein, Diemer, & Autin, 2016) was tested in samples of United States (n = 346) and Korean (n = 319) undergraduates. Participants completed measures of economic resources, work volition, career adaptability, occupational engagement, and future decent work perceptions. The results illustrated measurement invariance between the two samples. Thus, the hypothesized models were tested separately in the two samples and the results were compared regarding parameter significance, direction, and magnitude. Overall, the modified model generally fit well with both samples. However, there were notable cross-cultural differences: economic resources significantly predicted work volition, occupational engagement, and future decent work perceptions only in the United States sample and the future decent work perceptions and occupational engagement were negatively associated in the Korean sample. Explanations about the cross-cultural differences and invariances were provided and practical and research implications were discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Women attaining decent work: The important role of workplace climate in Psychology of Working Theory.

Grounded in Psychology of Working Theory (PWT), the current study investigated predictors of decent work among a sample of employed women (N = 528). A structural equation model was examined finding that women's experiences of marginalization, work volition, and career adaptability all directly predicted the attainment of decent work, and economic constraints and marginalization experiences indirectly predicted decent work via work volition. Additionally, workplace climate for women employees was examined as both a predictor and moderator variable to explore best positioning of this additive construct. Workplace climate did not significantly moderate any model paths; however, it was a unique predictor of work volition and decent work, suggesting that this construct may be better positioned as a predictor variable in understanding the work experiences of women. These results highlight the importance of further investigating the role of workplace climate in PWT as well as the need for refining our understanding of how marginalized employees achieve decent work. Implications of the present study's results are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Testing a critical cultural wealth model of well-being among first-generation students.

The current study examined predictors of career choice and life satisfaction among a diverse sample of first-generation college students (N = 424). Grounded in the critical cultural wealth model (CCWM; Garriott, 2019), financial stress, sense of belonging, and work volition were found to directly predict life satisfaction and work volition was found to directly predict career choice satisfaction. Additionally, work volition and/or a sense of belonging were found to significantly mediate the relation of financial stress and experiences of discrimination to career choice and life satisfaction. Invariance testing revealed that the model fit equally well for students identifying as a racial/ethnic minority compared with White students, for freshman/sophomores compared with juniors/seniors, and for students who were part of a first-generation scholarship program versus those who were not. Overall, findings suggest that first-generation students' sense of career choice and life satisfaction is predicted primarily by feelings of work volition and belonging on campus, each of which may be negatively affected by experiencing higher levels of financial stress or discrimination on campus. Implications for research and practice are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

An initial examination of the work as calling theory.

Over the past decade, research on work as a calling has seen a rapid growth, with hundreds of empirical articles on the topic having been published. Until recently, however, there has been no comprehensive theoretical model of work as a calling to guide research. Duffy, Dik, Douglass, England, and Velez (2018) published the Work as Calling Theory (WCT), which provides a comprehensive model of the predictors and outcomes of living out a calling. The present study provides the first empirical examination of the 20 propositions outlined within the predictor portion of this model. Using data collected from a sample of 424 employed adults living in the United States, from diverse social class backgrounds and occupations, we conducted latent variable structural equation modeling to evaluate the model propositions. Overall, we found full (17) and partial (1) support for 18 of the 20 model propositions, which included direct effects along with mediating and moderating effects. Person-environment fit, career commitment, and work meaning appear to be critical in helping to translate a perceived calling and access to opportunity into a lived calling. Additionally, calling motivation, organizational support, and job crafting may play a key role in helping employees with a calling experience more fit with their work environments. Taking these findings into consideration, we explore practical implications for career counselors and employers and highlight future directions for scholars using the WCT. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Application of the psychology of working theory with Korean emerging adults.

Psychology of Working Theory (PWT; Duffy, Blustein, Diemer, & Autin, 2016) is a recently developed framework aimed at documenting predictors and outcomes of decent work. To date, no studies have explored the applicability of the psychology of working perspective with emerging adults. The goal of the present study is to examine the predictor portion of PWT with a sample of Korean emerging adults from diverse economic backgrounds. Data were collected from a sample of 407 emerging adults attending a large junior college in Korea. Overall, most of the hypothesized direct paths were significant, with economic resources positively relating to both work volition and career adaptability and these positively relating to occupational engagement and future perceptions of securing decent work. Support for the hypothesized indirect effects was mixed. Overall, results suggest that the PWT is generally relevant and applicable to emerging adults when population-appropriate outcomes are included in the model and that the theory is supported in the Korean context. Based on the results, we also propose that interventions based on malleable psychological factors-the mediators in our study-may be targets when working with emerging adults experiencing economic constraints. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Two-dimensional grid optimization for sedimentation velocity analysis in the analytical ultracentrifuge.

Sedimentation velocity experiments performed in the analytical ultracentrifuge are modeled using finite-element solutions of the Lamm equation. During modeling, three fundamental parameters are optimized: the sedimentation coefficients, the diffusion coefficients, and the partial concentrations of all solutes present in a mixture. A general modeling approach consists of fitting the partial concentrations of solutes defined in a two-dimensional grid of sedimentation and diffusion coefficient combinations that cover the range of possible solutes for a given mixture. An increasing number of grid points increase the resolution of the model produced by the subsequent analysis, with denser grids giving rise to a very large system of equations. Here, we evaluate the efficiency and resolution of several regular grids and show that traditionally defined grids tend to provide inadequate coverage in one region of the grid, while at the same time being computationally wasteful in other sections of the grid. We describe a rapid and systematic approach for generating efficient two-dimensional analysis grids that balance optimal information content and model resolution for a given signal-to-noise ratio with improved calculation efficiency. These findings are general and apply to one- and two-dimensional grids, although they no longer represent regular grids. We provide a recipe for an improved grid-point spacing in both directions which eliminates unnecessary points, while at the same time providing a more uniform resolution that can be scaled based on the stochastic noise in the experimental data.

Methylglyoxal induced advanced glycation end products (AGE)/receptor for AGE (RAGE)-mediated angiogenic impairment in bone marrow-derived endothelial progenitor cells.

Endothelial cells (ECs) maintain the structure and function of blood vessels and are readily exposed to exogenous and endogenous toxic substances in the circulatory system. Bone marrow-derived endothelial progenitor cells (EPCs) circulate in the blood and differentiate to EC, which are known to participate in angiogenesis and regeneration of injured vessels. Dysfunction in EPC contributes to cardiovascular complications in patients with diabetes, but the precise molecular mechanisms underlying diabetic EPC abnormalities are not completely understood. The aim of this study was to investigate the mechanisms underlying diabetic EPC dysfunction using methylglyoxal (MG), an endogenous toxic diabetic metabolite. Data demonstrated that MG decreased cell viability and protein expression of vascular endothelial growth factor receptor (VEGFR)-2 associated with functional impairment of tube formation in EPC. The generation of advanced glycation end (AGE) products was increased in EPC following exposure to MG. Blockage of receptor for AGE (RAGE) by FPS-ZM1, a specific antagonist for RAGE, significantly reversed the decrease of VEGFR-2 protein expression and angiogenic dysfunction in MG-incubated EPC. Taken together, data demonstrated that MG induced angiogenic impairment in EPC via alterations in the AGE/RAGE-VEGFR-2 pathway which may be utilized in the development of potential therapeutic and preventive targets for diabetic vascular complications.

Bidirectional Regulation of GABAA Reversal Potential in the Adult Brain: Physiological and Pathological Implications.

In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABAA channels are permeable to anions, the reversal potential of GABAA is very close to that of Cl-, which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl-, respectively. Due to the closeness between GABAA reversal potential and the value of the resting membrane potential in most neurons, small changes in intracellular chloride have a major functional impact, which makes GABAA a uniquely flexible signaling system. In most neurons of the adult brain, the GABAA reversal potential is slightly more negative than the resting membrane potential, which makes GABAA hyperpolarizing. Alterations in GABAA reversal potential are a common feature in numerous conditions as they are the consequence of an imbalance in the NKCC1-KCC2 activity ratio. In most conditions (including Alzheimer's disease, schizophrenia, and Down's syndrome), GABAA becomes depolarizing, which causes network desynchronization and behavioral impairment. In other conditions (neonatal inflammation and neuropathic pain), however, GABAA reversal potential becomes hypernegative, which affects behavior through a potent circuit deactivation.

Hypernegative GABAA Reversal Potential in Pyramidal Cells Contributes to Medial Prefrontal Cortex Deactivation in a Mouse Model of Neuropathic Pain.

Deactivation of the medial prefrontal cortex (mPFC) has been broadly reported in both neuropathic pain models and human chronic pain patients. Several cellular mechanisms may contribute to the inhibition of mPFC activity, including enhanced GABAergic inhibition. The functional effect of GABAA(γ-aminobutyric acid type A)-receptor activation depends on the concentration of intracellular chloride in the postsynaptic neuron, which is mainly regulated by the activity of Na-K-2Cl cotransporter isoform 1 (NKCC1) and K-Cl cotransporter isoform 2 (KCC2), 2 potassium-chloride cotransporters that import and extrude chloride, respectively. Recent work has shown that the NKCC1-KCC2 ratio is affected in numerous pathological conditions, and we hypothesized that it may contribute to the alteration of mPFC function in neuropathic pain. We used quantitative in situ hybridization to assess the level of expression of NKCC1 and KCC2 in the mPFC of a mouse model of neuropathic pain (spared nerve injury), and we found that KCC2 transcript is increased in the mPFC of spared nerve injury mice while NKCC1 is not affected. Perforated patch recordings further showed that this results in the hypernegative reversal potential of the GABAA current in pyramidal neurons of the mPFC. Computational simulations suggested that this change in GABAA reversal potential is sufficient to significantly reduce the overall activity of the cortical network. Thus, our results identify a novel pathological modulation of GABAA function and a new mechanism by which mPFC function is inhibited in neuropathic pain. Our data also help explain previous findings showing that activation of mPFC interneurons has proalgesic effect in neuropathic, but not in control conditions. PERSPECTIVE: Chronic pain is associated with the presence of depolarizing GABAA current in the spinal cord, suggesting that pharmacological NKCC1 antagonism has analgesic effects. However, our results show that in neuropathic pain, GABAA current is actually hyperinhibitory in the mPFC, where it contributes to the mPFC functional deactivation. This suggests caution in the use of NKCC1 antagonism to treat pain.

Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration.

Tissue homeostasis is controlled by cellular circuits governing cell growth, organization, and differentation. In this study we identify previously undescribed cell-to-cell communication that mediates information flow from mechanosensitive pleural mesothelial cells to alveolar-resident stem-like tuft cells in the lung. We find mesothelial cells to express a combination of mechanotransduction genes and lineage-restricted ligands which makes them uniquely capable of responding to tissue tension and producing paracrine cues acting on parenchymal populations. In parallel, we describe a large population of stem-like alveolar tuft cells that express the endodermal stem cell markers Sox9 and Lgr5 and a receptor profile making them uniquely sensitive to cues produced by pleural Mesothelium. We hypothesized that crosstalk from mesothelial cells to alveolar tuft cells might be central to the regulation of post-penumonectomy lung regeneration. Following pneumonectomy, we find that mesothelial cells display radically altered phenotype and ligand expression, in a pattern that closely tracks with parenchymal epithelial proliferation and alveolar tissue growth. During an initial pro-inflammatory stage of tissue regeneration, Mesothelium promotes epithelial proliferation via WNT ligand secretion, orchestrates an increase in microvascular permeability, and encourages immune extravasation via chemokine secretion. This stage is followed first by a tissue remodeling period, characterized by angiogenesis and BMP pathway sensitization, and then a stable return to homeostasis. Coupled with key changes in parenchymal structure and matrix production, the cumulative effect is a now larger organ including newly-grown, fully-functional tissue parenchyma. This study paints Mesothelial cells as a key orchestrating cell type that defines the boundary of the lung and exerts critical influence over the tissue-level signaling state regulating resident stem cell populations. The cellular circuits unearthed here suggest that human lung regeneration might be inducible through well-engineered approaches targeting the induction of tissue regeneration and safe return to homeostasis.

Impaired muscarinic modulation of the rat prelimbic cortex in neuropathic pain is sexually dimorphic and associated with cold allodynia.

Cholinergic modulation of the brain cortex is critical for cognitive processes, and altered cholinergic modulation of the prefrontal cortex is emerging as an important mechanism of neuropathic pain. Sex differences in pain prevalence and perception are well known, yet the precise nature of the mechanisms responsible for sexual dimorphism in chronic neuropathic pain are poorly understood. Here we investigated potential sex differences in cholinergic modulation of layer five commissural pyramidal neurons of the rat prelimbic cortex in control conditions and in the SNI model of neuropathic pain. We discovered that cholinergic modulation is stronger in cells from male compared with female rats, and that in neuropathic pain rats, cholinergic excitation of pyramidal neurons was more severely impaired in males than in females. Finally, we found that selective pharmacological blockade of the muscarinic M1 subunit in the prefrontal cortex induces cold sensitivity (but not mechanical allodynia) in naïve animals of both sexes.

Improved visibility of illuminated chopper-assisted cataract surgery involving iris challenges.

Purpose: The aim of this study was to evaluate the efficacy of the illuminated chopper-assisted cataract surgery in terms of shortening the surgical time and reducing the use of pupil expansion devices in eyes with iris challenges. Methods: This was a retrospective case series of a university hospital. Four hundred forty-three eyes of 433 consecutive patients who underwent illuminated chopper-assisted cataract surgery were included in this study. Cases with preoperative or intraoperative miosis, iris prolapse, and intraoperative floppy iris syndrome were included in the iris challenge group. Use of tamsulosin, iris hooks, pupil size, surgical time, and improved visibility (100/surgical time × pupil size) were compared between eyes with and without iris challenges. Mann-Whitney U test, Pearson's Chi-square test, and Fisher's exact test were used for statistical analysis. Results: Of 443 eyes, 66 were included in the iris challenge group (14.9%). Tamsulosin use was more common in patients with iris challenges and iris hooks were used more frequently (9.1% vs. 0%, P < 0.001) in patients with iris challenges than in those without iris challenges. Pupil size was smaller in patients with iris challenges (6.01 vs. 7.64 mm, P < 0.001). However, surgical time was not different (16.9 vs. 16.5 min, P = 0.064) between the two groups. As a result, improved visibility was calculated to be higher in patients with iris challenges (1.05 vs. 0.81, P < 0.001). Conclusion: In terms of surgical time and improved visibility, using the illuminated chopper simplified cataract surgery involving iris challenges. The use of an illuminated chopper is expected to be a good solution for challenging cataract surgeries.

Mono-(2-ethylhexyl)-phthalate potentiates methylglyoxal-induced blood-brain barrier damage via mitochondria-derived oxidative stress and bioenergetic perturbation.

Phthalates in contaminated foods and personal care products are one of the most frequently exposed chemicals with a public health concern. Phthalate exposure is related to cardiovascular diseases, including diabetic vascular complications and cerebrovascular diseases, yet the mechanism is still unclear. The blood-brain barrier (BBB) integrity disruption is strongly associated with cardiovascular and neurological disease exacerbation. We investigated BBB damage by di-(2-ethylhexyl) phthalate (DEHP) or its metabolite mono-(2-ethylhexyl) phthalate (MEHP) using brain endothelial cells and rat models. BBB damage by the subthreshold level of MEHP, but not a DEHP, significantly increased by the presence of methylglyoxal (MG), a reactive dicarbonyl compound whose levels increase in the blood in hyperglycemic conditions in diabetic patients. Significant potentiation in apoptosis and autophagy activation, mitochondria-derived reactive oxygen species (ROS) production, and mitochondrial metabolic disturbance were observed in brain ECs by co-exposure to MG and MEHP. N-acetyl cysteine (NAC) restored autophagy activation as well as tight junction protein impairment induced by co-exposure to MG and MEHP. Intraperitoneal administration of MG and MEHP significantly altered mitochondrial membrane potential and tight junction integrity in rat brain endothelium. This study may provide novel insights into enhancing phthalate toxicity in susceptible populations, such as diabetic patients.

A phenomenological model of proton FLASH oxygen depletion effects depending on tissue vasculature and oxygen supply.

Introduction: Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning. Methods: The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries. Results: Dynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radio-resistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 µm vasculature spacing and 18.9 µM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect. Conclusion: We developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments.

Raw starch fermentation to ethanol by an industrial distiller's yeast strain of Saccharomyces cerevisiae expressing glucoamylase and α-amylase genes.

Industrial strains of a polyploid, distiller's Saccharomyces cerevisiae that produces glucoamylase and α-amylase was used for the direct fermentation of raw starch to ethanol. Strains contained either Aspergillus awamori glucoamylase gene (GA1), Debaryomyces occidentalis glucoamylase gene (GAM1) or D. occidentalis α-amylase gene (AMY), singly or in combination, integrated into their chromosomes. The strain expressing both GA1 and AMY generated 10.3% (v/v) ethanol (80.9 g l(-1)) from 20% (w/v) raw corn starch after 6 days of fermentation, and decreased the raw starch content to 21% of the initial concentration.