American Agribusiness & Biotechnology: A New Era of Farming

In the past fifty years there has been an incredible amount of change made to the agrarian system of the United States. New discoveries in the realm of biotechnology led to the adoption of genetically modified organisms (GMOs) in agriculture, and transformed the industry. Due to regulatory policies set during the nineteen-eighties this technology was able to benefit from widespread commercialization. Today, we see the effects of this approach and are entering into a highly volatile political climate in regard to GMOs. This paper aims to provide an analysis of the regulatory system in place and the discrepancies that exist in US policy. The factors evaluated through this thesis include the current US regulatory approach, advancements in biotechnology, and a comparative perspective on US and EU systems. In each of these reviews it is also relevant to mention consumer opinion on GMOs and the role of interest groups. It is important for every American consumer to understand the politics and technology behind their meals. Through the analysis of recent judicial decisions and the enactment of new laws this thesis explains how the use of GMOs in agriculture is causing an unprecedented change to the political structures in place

Extrathoracic airway hyperresponsiveness as a mechanism of post infectious cough: case report

Post-infectious cough is a common diagnosis in people with chronic cough. However, the specific infectious aetiology and cough mechanisms are seldom identified

Chronic cough and laryngeal dysfunction improve with specific treatment of cough and paradoxical vocal fold movement

Rationale: Chronic persistent cough can be associated with laryngeal dysfunction that leads to symptoms such as dysphonia, sensory hyperresponsiveness to capsaicin, and motor dysfunction with paradoxical vocal fold movement and variable extrathoracic airflow obstruction (reduced inspiratory airflow). Successful therapy of chronic persistent cough improves symptoms and sensory hyperresponsiveness. The effects of treatment for chronic cough on laryngeal dysfunction are not known. Objective: The aim of this study was to investigate effects of therapy for chronic cough and paradoxical vocal fold movement. Methods: Adults with chronic cough (n = 24) were assessed before and after treatment for chronic persistent cough by measuring quality of life, extrathoracic airway hyperresponsiveness to hypertonic saline provocation, capsaicin cough reflex hypersensitivity and fibreoptic laryngoscopy to observe paradoxical vocal fold movement. Subjects with chronic cough were classified into those with (n = 14) or without (n = 10) paradoxical vocal fold movement based on direct observation at laryngoscopy. Results: Following treatment there was a significant improvement in cough related quality of life and cough reflex sensitivity in both groups. Subjects with chronic cough and paradoxical vocal fold movement also had additional improvements in extrathoracic airway hyperresponsiveness and paradoxical vocal fold movement. The degree of improvement in cough reflex sensitivity correlated with the improvement in extrathoracic airway hyperresponsiveness. Conclusion: Laryngeal dysfunction is common in chronic persistent cough, where it is manifest as paradoxical vocal fold movement and extrathoracic airway hyperresponsiveness. Successful treatment for chronic persistent cough leads to improvements in these features of laryngeal dysfunction

The uniqueome: a mappability resource for short-tag sequencing

Summary: Quantification applications of short-tag sequencing data (such as CNVseq and RNAseq) depend on knowing the uniqueness of specific genomic regions at a given threshold of error. Here, we present the ‘uniqueome’, a genomic resource for understanding the uniquely mappable proportion of genomic sequences. Pre-computed data are available for human, mouse, fly and worm genomes in both color-space and nucletotide-space, and we demonstrate the utility of this resource as applied to the quantification of RNAseq data

Cough reflex sensitivity improves with speech language pathology management of refractory chronic cough

Rationale: Speech language pathology is an effective management intervention for chronic cough that persists despite medical treatment. The mechanism behind the improvement has not been determined but may include active cough suppression, reduced cough sensitivity or increased cough threshold from reduced laryngeal irritation. Objective measures such as cough reflex sensitivity and cough frequency could be used to determine whether the treatment response was due to reduced underlying cough sensitivity or to more deliberate control exerted by individual patients. The number of treatments required to effect a response was also assessed. Objective: The aim of this study was to investigate subjective and objective measures of cough before, during and after speech language pathology treatment for refractory chronic cough and the mechanism underlying the improvement. Methods: Adults with chronic cough (n = 17) were assessed before, during and after speech language pathology intervention for refractory chronic cough. The primary outcome measures were capsaicin cough reflex sensitivity, automated cough frequency detection and cough-related quality of life. Results: Following treatment there was a significant improvement in cough related quality of life (Median (IQR) at baseline: 13.5 (6.3) vs. post treatment: 16.9 (4.9), p = 0.002), objective cough frequency (Mean ± SD at baseline: 72.5 ± 55.8 vs. post treatment: 25 ± 27.9 coughs/hr, p = 0.009), and cough reflex sensitivity (Mean ± SD log C5 at baseline: 0.88 ± 0.48 vs. post treatment: 1.65 ± 0.88, p < 0.0001). Conclusions: This is the first study to show that speech language pathology management is an effective intervention for refractory chronic cough and that the mechanism behind the improvement is due to reduced laryngeal irritation which results in decreased cough sensitivity, decreased urge to cough and an increased cough threshold. Speech language pathology may be a useful and sustained treatment for refractory chronic cough. Trial Registration: Australian New Zealand Clinical Trials Register, ACTRN12608000284369

Decision Support Algorithm for Evaluating Carbon Dioxide Emissions from Electricity Generation in the United States

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146433/1/jiec12708.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146433/2/jiec12708-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146433/3/jiec12708_am.pd

NOTCH1 inhibition in vivo results in mammary tumor regression and reduced mammary tumorsphere-forming activity in vitro

INTRODUCTION: NOTCH activation has been recently implicated in human breast cancers, associated with a poor prognosis, and tumor-initiating cells are hypothesized to mediate resistance to treatment and disease relapse. To address the role of NOTCH1 in mammary gland development, transformation, and mammary tumor-initiating cell activity, we developed a doxycycline-regulated mouse model of NOTCH1-mediated mammary transformation. METHODS: Mammary gland development was analyzed by using whole-mount analysis and by flow cytometry in nulliparous transgenic mice maintained in the presence/absence of doxycycline (or intracellular NOTCH1). Mammary tumors were examined histologically and immunophenotyped by staining with antibodies followed by flow cytometry. Tumors were transplanted into mammary fat pads under limiting dilution conditions, and tumor-initiating cell frequency was calculated. Mammary tumor cells were also plated in vitro in a tumorsphere assay in the presence/absence of doxycycline. RNA was isolated from mammary tumor cell lines cultured in the presence/absence of doxycycline and used for gene-expression profiling with Affymetrix mouse arrays. NOTCH1-regulated genes were identified and validated by using quantitative real-time polymerase chain reaction (PCR). Mammary tumor-bearing mice were treated with doxycycline to suppress NOTCH1 expression, and disease recurrence was monitored. RESULTS: Similar to published studies, we show that constitutive expression of human intracellular NOTCH1 in the developing mouse mammary gland inhibits side branching and promotes luminal cell fate. These mice develop mammary adenocarcinomas that express cytokeratin (CK) 8/18. In vivo limiting-dilution analyses revealed that these mammary tumors exhibit functional heterogeneity and harbor a rare (1/2,978) mammary tumor-initiating cell population. With this dox-regulated NOTCH1 mammary tumor model, we demonstrate that NOTCH1 inhibition results in mammary tumor regression in vivo and prevents disease recurrence in four of six tumors tested. Consistent with the in vivo data, NOTCH1 inhibition reduces mammary tumorsphere activity in vitro. We also identify the embryonic stem cell transcription factor Nanog as a novel NOTCH1-regulated gene in tumorspheres and in mouse and human breast cancer cell lines. CONCLUSIONS: These data indicate that NOTCH1 inhibition results in mammary tumor regression in vivo and interferes with disease recurrence. We demonstrate that NOTCH1-transformed mouse mammary tumors harbor a rare mammary tumor-initiating population and that NOTCH1 contributes to mammary tumor-initiating activity. This work raises the possibility that NOTCH therapeutics may target mammary tumor-initiating cells in certain human breast cancer subtypes

Alterations to the Gastrointestinal Microbiome Associated with Methamphetamine Use among Young Men who have Sex with Men.

Methamphetamine (MA) use is a major public health problem in the United States, especially among people living with HIV (PLWH). Many MA-induced neurotoxic effects are mediated by inflammation and gut microbiota may play a role in this process, yet the effects of MA on the microbiome have not been adequately explored. Therefore, we performed 16S rRNA gene sequencing on rectal swab samples from 381 men who have sex with men, 48% of whom were PLWH and 41% of whom used MA. We compared microbiome composition between MA users and non-users while testing for potential interactions with HIV and controlling for numerous confounders using inverse probability of treatment weighting. We found that MA use explained significant variation in overall composition (R2 = 0.005, p = 0.008) and was associated with elevated Finegoldia, Parvimonas, Peptoniphilus, and Porphyromonas and reduced Butyricicoccus and Faecalibacterium, among others. Genera including Actinomyces and Streptobacillus interacted with HIV status, such that they were increased in HIV+ MA users. Finegoldia and Peptoniphilus increased with increasing frequency of MA use, among others. In summary, MA use was associated with a microbial imbalance favoring pro-inflammatory bacteria, including some with neuroactive potential and others that have previously been associated with poor HIV outcomes

Electrospinning nonspinnable sols to ceramic fibers and springs

Electrospinning has been applied to produce ceramic fibers using sol gel-based spinning solutions consisting of ceramic precursors, a solvent, and a polymer to control the viscosity of the solution. However, the addition of polymers to the spinning solution makes the process more complex, increases the processing time, and results in porous mechanically weak ceramic fibers. Herein, we develop a coelectrospinning technique, where a nonspinnable sol (2, ZrO2, SiO2, and Al2O3. The polycrystalline TiO2 fibers possess excellent flexibility and a high Young's modulus reaching 54.3 MPa, solving the extreme brittleness problem of the previously reported TiO2 fibers. The single-component ZrO2 fibers exhibit a Young's modulus and toughness of 130.5 MPa and 11.9 KJ/m3, respectively, significantly superior to the counterparts prepared by conventional sol-gel electrospinning. We also report the creation of ceramic fibers in micro- and nanospring morphologies and examine the formation mechanisms using thermomechanical simulations. The fiber assemblies constructed by the helical fibers exhibit a density-normalized toughness of 3.5-5 times that of the straight fibers due to improved fracture strain. This work expands the selection of the electrospinning solution and enables the development of ceramic fibers with more attractive properties