The effects of the U.S. Plant Variety Protection Act on wheat genetic improvement:

The U.S. Plant Variety Protection Act (PVPA) of 1970 was meant to strengthen intellectual property protection for plant breeders. A model of investment under partial excludability is developed, leading to the hypotheses that any increase in excludability or appropriability of the returns to invention, attributable to the PVPA, would lead to increases in investment or efficiency gains in varietal R&D, improved varietal quality, and enhanced royalties. These hypotheses are tested in an economic analysis of the effects of the PVPA on wheat genetic improvement. The PVPA appears to have contributed to increases in public expenditures on wheat variety improvement, but private-sector investment in wheat breeding does not appear to have increased. Moreover, econometric analyses indicate that the PVPA has not caused any increase in experimental or commercial wheat yields. However, the share of U.S. wheat acreage sown to private varieties has increased–from 3 percent in 1970 to 30 percent in the 1990s. These findings indicate that the PVPA has served primarily as a marketing tool with little impact on excludability or appropriability.Intellectual property., Plant breeding., Wheat., Economics.,

HIV-1 Group M Subtype Fitness, Disease Progression, and Entry Efficiency

Human immunodeficiency virus type 1 (HIV-1) emerged in the human population shortly after the turn of the 19th century. Distribution of HIV-1 across the globe over the past 30–35 years can be traced to founder events with primordial HIV strains from sub-Saharan Africa. Even considering the burden of HIV in Africa, our knowledge of HIV-1 disease is still largely limited to subtype B HIV-1, a strain responsible for 3 million infections in North America and Europe as compared to the 33 million that are infected with HIV-1 subtypes A, C, D, and circulating and unique recombinant forms. This dissertation analyzes data and archived samples from a cohort of HIV+ women in Uganda and Zimbabwe to assess the role of HIV-1 Group M subtype in disease progression, viral replicative fitness and cellular entry efficiency. Generalized estimating equation models are employed to calculate average rates of CD4+ T-cell loss over the course of disease, investigate circulating viral load, and compare depletion of memory T-cell subsets in CD4+ and CD8+ T-cells. Fluorescent tissue culture assays of HIV-1 entry were used to phenotypically evaluate entry efficiency and its association with replicative fitness. Ugandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D, a difference not associated with any other clinical parameters. Relative replicative fitness and entry efficiency of HIV-1 variants directly correlated with virulence in the patients, subtype D \u3e A \u3e C. These relationships were maintained in both assays evaluating HIV-induced cell-fusion rates, viral particle entry rates and CD4 receptor affinity. The primary burden of HIV infection is placed on T-cell memory populations that are focal points for progeny virion production, the latent proviral reservoir, and immune activation. All subtypes depleted effector memory T-cells preferentially, however subtype D infections lost these cells at about twice the rate of subtype C infections. Finally, subtype D was found to uniquely deplete CD8+ memory T-cells

Genetic Activation, Inactivation, and Deletion Reveal a Limited And Nuanced Role for Somatostatin-Containing Basal Forebrain Neurons in Behavioral State Control

Recent studies have identified an especially important role for basal forebrain GABAergic (BF(VGAT)) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF(VGAT) neurons comprise several neurochemically and anatomically distinct subpopulations, including parvalbumin-containing BF(VGAT) neurons and somatostatin-containing BF(VGAT) neurons (BF(SOM) neurons), and it was recently reported that optogenetic activation of BF(SOM) neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the rest period of the animal. This finding was unexpected given that most BF(SOM) neurons are not NREM sleep active and that central administration of the synthetic somatostatin analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we used a combination of genetically driven chemogenetic and optogenetic activation, chemogenetic inhibition, and ablation approaches to further explore the in vivo role of BF(SOM) neurons in arousal control. Our findings indicate that acute activation or inhibition of BF(SOM) neurons is neither wakefulness nor NREM sleep promoting and is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24 h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF(SOM) neurons, specifically suggesting at least two distinct subpopulations. Together, our data support the more nuanced view that BF(SOM) neurons are electrically heterogeneous and are not NREM sleep or wake promoting per se, but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry.SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide range of higher-level neurobiological processes, including regulating and maintaining normal levels of electrocortical and behavioral arousal. The respective in vivo roles of BF cell populations and their neurotransmitter systems in the regulation of electrocortical and behavioral arousal remains incompletely understood. Here we seek to define the neurobiological contribution of GABAergic somatostatin-containing BF neurons to arousal control. Understanding the respective contribution of BF cell populations to arousal control may provide critical insight into the pathogenesis of a host of neuropsychiatric and neurodegenerative disorders, including Alzheimer\u27s disease, Parkinson\u27s disease, schizophrenia, and the cognitive impairments of normal aging

A grid-enabled problem solving environment for parallel computational engineering design

This paper describes the development and application of a piece of engineering software that provides a problem solving environment (PSE) capable of launching, and interfacing with, computational jobs executing on remote resources on a computational grid. In particular it is demonstrated how a complex, serial, engineering optimisation code may be efficiently parallelised, grid-enabled and embedded within a PSE. The environment is highly flexible, allowing remote users from different sites to collaborate, and permitting computational tasks to be executed in parallel across multiple grid resources, each of which may be a parallel architecture. A full working prototype has been built and successfully applied to a computationally demanding engineering optimisation problem. This particular problem stems from elastohydrodynamic lubrication and involves optimising the computational model for a lubricant based on the match between simulation results and experimentally observed data

Reassessing the Role of Histaminergic Tuberomammillary Neurons in Arousal Control

The histaminergic neurons of the tuberomammillary nucleus (TMN(HDC)) of the posterior hypothalamus have long been implicated in promoting arousal. More recently, a role for GABAergic signaling by the TMN(HDC) neurons in arousal control has been proposed. Here, we investigated the effects of selective chronic disruption of GABA synthesis (via genetic deletion of the GABA synthesis enzyme, glutamic acid decarboxylase 67) or GABAergic transmission (via genetic deletion of the vesicular GABA transporter (VGAT)) in the TMN(HDC) neurons on sleep-wake in male mice. We also examined the effects of acute chemogenetic activation and optogenetic inhibition of TMN(HDC) neurons upon arousal in male mice. Unexpectedly, we found that neither disruption of GABA synthesis nor GABAergic transmission altered hourly sleep-wake quantities, perhaps because very few TMN(HDC) neurons coexpressed VGAT. Acute chemogenetic activation of TMN(HDC) neurons did not increase arousal levels above baseline but did enhance vigilance when the mice were exposed to a behavioral cage change challenge. Similarly, acute optogenetic inhibition had little effect upon baseline levels of arousal. In conclusion, we could not identify a role for GABA release by TMN(HDC) neurons in arousal control. Further, if TMN(HDC) neurons do release GABA, the mechanism by which they do so remains unclear. Our findings support the view that TMN(HDC) neurons may be important for enhancing arousal under certain conditions, such as exposure to a novel environment, but play only a minor role in behavioral and EEG arousal under baseline conditions.SIGNIFICANCE STATEMENT The histaminergic neurons of the tuberomammillary nucleus of the hypothalamus (TMN(HDC)) have long been thought to promote arousal. Additionally, TMN(HDC) neurons may counter-regulate the wake-promoting effects of histamine through co-release of the inhibitory neurotransmitter, GABA. Here, we show that impairing GABA signaling from TMN(HDC) neurons does not impact sleep-wake amounts and that few TMN(HDC) neurons contain the vesicular GABA transporter, which is presumably required to release GABA. We further show that acute activation or inhibition of TMN(HDC) neurons has limited effects upon baseline arousal levels and that activation enhances vigilance during a behavioral challenge. Counter to general belief, our findings support the view that TMN(HDC) neurons are neither necessary nor sufficient for the initiation and maintenance of arousal under baseline conditions

Passive Tracer Visualization to Simulate Aerodynamic Virus Transport in Noninvasive Respiratory Support Methods

BACKGROUND: Various forms of noninvasive respiratory support methods are used in the treatment of hypoxemic CO­VID-19 patients, but limited data are available about the corresponding respiratory droplet dispersion. OBJECTIVES: The aim of this study was to estimate the potential spread of infectious diseases for a broad selection of oxygen and respiratory support methods by revealing the therapy-induced aerodynamics and respiratory droplet dispersion. METHODS: The exhaled air-smoke plume from a 3D-printed upper airway geometry was visualized by recording light reflection during simulated spontaneous breathing, standard oxygen mask application, nasal high-flow therapy (NHFT), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP). The dispersion of 100 μm particles was estimated from the initial velocity of exhaled air and the theoretical terminal velocity. RESULTS: Estimated droplet dispersion was 16 cm for unassisted breathing, 10 cm for Venturi masks, 13 cm for the nebulizer, and 14 cm for the nonrebreathing mask. Estimated droplet spread increased up to 34 cm in NHFT, 57 cm in BiPAP, and 69 cm in CPAP. A nonsurgical face mask over the NHFT interface reduced estimated droplet dispersion. CONCLUSIONS: During NHFT and CPAP/BiPAP with vented masks, extensive jets with relatively high jet velocities were observed, indicating increased droplet spread and an increased risk of droplet-driven virus transmission. For the Venturi masks, a nonrebreathing mask, and a nebulizer, estimated jet velocities are comparable to unassisted breathing. Aerosols are transported unboundedly in all these unfiltered therapies. The adequate use of protective measures is of vital importance when using noninvasive unfiltered therapies in infectious respiratory diseases