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Leafy spurge, a noxious perennial weed, is a major threat to the prairie ecosystem in North America. Strategic planning to control leafy spurge requires monitoring its spatial distribution and spread. In this study, the ability to detect flowering leafy spurge at two biological control sites in southern Saskatchewan, Canada was investigated using an unmanned aerial vehicle system (UAVs). Three flight missions were conducted on June 30, 2016 during the leafy spurge flowering period. Imagery was acquired at four flight heights and one or two acquisition times depending on the site. The sites were re-flown on June 28, 2017 to evaluate the change in flowering leafy spurge over time. Mixed Tuned Match Filtering (MTMF) and Hue, Intensity and Saturation (HIS) threshold analyses were used to determine flowering leafy spurge cover. The results showed the flight height of 30 m was optimal as the strongest relationships between UAV and ground estimates of both leafy spurge cover (r2=0.76 to 0.90, NRMSE=0.10 to 0.13) and stem density (r2=0.72 to 0.75) were observed. The flowering leafy spurge detection was not significantly affected by the image analysis method (p>0.05). Flowering leafy spurge cover estimates were similar using HIS (1.9% to 14.8%) and MTMF (2.1% to 10.3%) and were in agreement with the ground estimates (r2=0.64 to 0.93, NRMSE=0.08 to 0.25 using HIS and r2 =0.64 to 0.90, NRMSE=0.10 to 0.27 using MTMF). The reduction in flowering leafy spurge cover between 2016 and 2017 detected using the UAV images and HIS (8.1% at site 1 and 2.7% at site 2) was consistent with that based on ground digital photographs (10% at site 1 and 1.8% at site 2). This study shows UAV imagery is a useful tool for accurately detecting flowering leafy spurge and could be used for routine monitoring purposes in a biological control program.
In this paper, an improved quantification technique for STEM/EDX measurements of 1D dopant profiles based on the Cliff-Lorimer equation is presented. The technique uses an iterative absorption correction procedure based on density models correlating the local mass density and composition of the specimen. Moreover, a calibration and error estimation procedure based on linear regression and error propagation is proposed in order to estimate the total measurement error in the dopant density. The proposed approach is applied to the measurement of the As profile in a nanodevice test structure. For the calibration, two crystalline Si specimens implanted with different As doses have been used, and the calibration of the Cliff-Lorimer coefficients has been carried out using Rutherford Back Scattering measurements. The As profile measurement has been carried out on an FinFET test structure, showing that quantitative results can be obtained in the nanometer scale and for dopant atomic densities lower than 1%. Using the proposed approach, the measurement error and detection limit for our experimental setup are calculated and the possibility to improve this limit by increasing the observation time is discussed.
In the Federal Republic of Germany, intentional alteration of the genome of germline cells and embryos is prohibited by criminal law. This ban is the result of legislation that was adopted more than twenty-five years ago. However, the rapid emergence of genome manipulation techniques, coupled with recent technological developments, is increasingly exposing the senescence of the regulatory framework. With the advent of genome editing, there has been a shift in the national debate on the use of genetic engineering. Until recently, the discussion regarding the use of genome altering methods had been more about the application of genetic engineering to plants (so-called ‘green genetic engineering’) than to humans (so-called ‘red genetic engineering’). After all, green genetic engineering has been present in the fields for years, and sometimes even on the plate, while most red genetic engineering efforts have been unspectacular cell biology basic research, slowed down by both technical and legal hurdles. However, the emergence of more precise, safer and more predictable genome editing methods has now brought the issue into German public discourse and, as evidenced by this volume, around the world.
In France, civil law provisions on research involving human subjects, on donation and use of human body parts, and on medically assisted reproduction – originally developed between 1988 and 1994 and generally referred to as loi de bioéthique (law on bioethics) – specify whether and under which statutory conditions activities potentially leading to human germline genome modification can be undertaken. International law, including European law, poses further conditions. This chapter explores legislative and regulatory constraints on this type of research in France, analyzing how they developed over time to reach their present state. We will show that, in France, it is prohibited to create a human embryo solely for research purposes; that, however, research activities on supernumerary embryos and human embryonic stem cells are possible upon authorization by the national agency on biomedicine; but that, nevertheless, alterations to the genome of an embryo under circumstances that allow the modifications to pass on to future generations (i.e. through a successful pregnancy) are strictly prohibited. A peculiar feature of French legislation in this domain is that the law on bioethics is regularly updated in light of new technological or scientific developments, and as a result of a national public consultation held at least every five years. In 2018 one such rounds of public consultation took place, and a report summarizing its outcome is now being considered as the basis for possible legislative reform – including in the domain of genetic engineering. While it is not possible to anticipate future legislative developments, the report signals some degree of openness in the French civil society regarding the use of genetic engineering and genome editing, at least in the context of research.
The use of genetic technologies for reproductive, farming, agricultural and scientific purposes has long been a matter of public concern in Switzerland. As a result of a series of legislative initiatives at the federal level, as well as of popular referenda, the country developed one of the most restrictive regulatory environments in Europe for research, potentially leading to human germline genome modification. In particular, any genetic manipulation of reproductive cells or embryos is strictly forbidden, regardless its intended purpose. This chapter will illustrate the way constitutional- and federal-level legislation, as well as international law and regulatory provisions rigidly constrain research activities that could potentially lead to genetic alterations in humans and their progeny. In such a restrictive context, it is highly unlikely that recent technical advances in genetic engineering and genome editing will be employed to produce germline genome modifications for either medical or purely scientific purposes. Furthermore, while the Swiss National Advisory Commission for Biomedical Ethics has recently expressed partial support for basic research possibly involving the genetic modification of human embryos, there are currently no indications that legislative initiatives will be undertaken to ease current regulations on such controversial matters.
Taking advantage of recent advances in parallel computing, we studied compositional disorder along metal–oxygen atomic columns in a complex Mo,V-oxide bronze using multislice frozen-phonon calculations. Commonly, the virtual crystal approximation (VCA) is used to model compositional disorder at crystallographic sites in a unit cell for a number of different theoretical and experimental techniques. In the VCA, a weighted linear sum of atomic properties is used to approximate the model structure. When using the VCA, the extracted V content of Mo,V–O columns from experimental high-angle annular dark-field (HAADF) images will be about half the V content estimated from simulations, considering the distinct cation ordering. This discrepancy is larger than the spread of HAADF signals of different configurational orders at a given V concentration, which can be up to 20%. Certain “isophilic” atomic arrangements along the column can be distinguished from more random ones using HAADF-STEM imaging. The trends and ratios of the simulated intensity spreads due to different compositional ordering along 11 M–O columns along the c-axis of the Mo,V oxide bronze qualitatively match those observed in experimental HAADF-STEM data. Instrumental and sample-based noise adds to the variability but does not significantly distort the relative ratios of column intensity variation. We observed that we only required seven random configurations to represent the intensity variations along columns.
Despite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.
To analyse how the auditory brainstem response changes in patients with sudden sensorineural hearing loss.
Data were collected via retrospective medical chart review.
Forty-three patients were included in this study. The mean latency of auditory brainstem response wave 1 was significantly longer for the affected side than for the unaffected side (p = 0.003). The mean latency of auditory brainstem response wave 1 was significantly shorter, and the mean amplitude of auditory brainstem response wave 1 was significantly larger, in the good response group compared to the poor response group. In forward conditional logistic regression analysis, auditory brainstem response wave 1 latency was an independent predictor of a good response (odds ratio = 34.37, 95 per cent confidence interval = 1.56–757.15, p = 0.025).
In patients with sudden sensorineural hearing loss, the latency of wave 1 of the auditory brainstem response was significantly increased and was related to prognosis.
The chapter discusses the relationship between patent governance, ethics, and democracy, referring to limits in patent law set in democratic decisions by the EU legislator in the EU Biotech Directive. The ordre public clauses in Articles 5 and 6 attempt to "upstream" ethics and anticipatory impact assessment in biotechnology patent law. However, the interpretation of these clauses, especially for inventions concerning human embryonic stem cells, gametes, parthenotes, and genome editing (CRISPR-Cas) techniques, has ignited intense policy debates. Granting practices and case law of the European Patent Office (EPO) and its Boards of Appeal have circumvented some of these legal restrictions, and thus pose challenges for transparency and accountability norms in patent practice. Case law of the Court of Justice of the European Union (CJEU) and empirical analyses of patent application and granting practices are scrutinised. The chapter states that interpretation of legal statutes must not be narrowly literal but must also include the history and purpose of the Biotech Directive and the socio-technical and economic implications of its application. This requires that the EPO and the European Commission act transparently and account for their application of the legal rules as set by the European legislator and interpreted by the CJEU.
Multiple sclerosis is the leading non-traumatic cause of disability in young adults, affecting up to 100,000 Canadians. This chronic inflammatory and neurodegenerative disease of the central nervous system leads to irreversible neurologic disability if inadequately controlled. Though many current medications are available that reduce inflammatory damage, most patients continue to show some evidence of disease activity and accrue disability. In this review, we discuss the role of immune ablation followed by autologous hematopoietic stem cell transplantation (AHSCT), a therapeutic option for select patients with a more aggressive disease course. By “resetting” the immune system with a variety of ablative conditioning regimens, followed by immune reconstitution, this therapy has shown a durable response in halting evidence of inflammatory activity in most patients, without the need for continued disease-modifying therapies (DMT). Since the introduction of this therapy, there have been advances in patient selection and supportive care, such that morbidity has significantly declined and treatment-related mortality is minimized. Recent phase-II trials have shown excellent results in efficacy and safety of AHSCT; however, challenges exist which require ongoing study. The future challenges include comparing the variety of AHSCT conditioning regimens with each other as well as with existing highly effective DMT; identifying patients with an aggressive disease course through novel biomarkers who may benefit the most from AHSCT; and surveillance of long-term outcomes of different treatment protocols. In select patients, replacing the immune system with AHSCT holds promise of fundamentally altering the trajectory of their aggressive disease course.
Androgenetic embryonic stem (AgES) cells offer a possible tool for patient-specific pluripotent stem cells that will benefit genomic imprinting studies and clinic applications. However, the difficulty in producing androgenetic embryos and the unbalanced expression of imprinted genes make the therapeutic applicability of AgES cells uncertain. In this study, we produced androgenetic embryos by injecting two sperm into an enucleated metaphase II (MII) oocyte. By this method, 88.48% of oocytes survived after injection, and 20.24% of these developed to the blastocyst stage. We successfully generated AgES cell lines from the androgenetic embryos and assayed the expression of imprinted genes in the cell lines. We found that the morphological characteristics of AgES cells were similar to that of fertilized embryonic stem cells (fES), such as expression of key pluripotent markers, and generation of cell derivatives representing all three germ layers following in vivo and in vitro differentiation. Furthermore, activation of paternal imprinted genes was detected, H19, ASC12 and Tss3 in AgES cell activation levels were lower while other examined genes showed no significant difference to that of fES cells. Interestingly, among examined maternal imprinted genes, only Mest and Igf2 were significantly increased, while levels of other detected genes were no different to that of fES cells. These results demonstrated that activation of some paternal imprinted genes, as well as recovery of maternal imprinted genes, was present in AgES cells. We differentiated AgES cells into a beating embryoid body in vitro, and discovered that the AgES cells did not show significant higher efficiency in myocardial differentiation potential.
Few studies have investigated alterations of olfactory neuroepithelium (ONE) as a biomarker of schizophrenia, and none its association with cognitive functioning.
Fresh ONE cells from twelve patients with schizophrenia and thirteen healthy controls were collected by nasal brushing, cultured in proper media and passed twelve times. Markers of cell proliferation (BrdU incorporation, Cyclin-D1 and p21 protein level) were quantified.Cognitive function was measured using Brief Neuropsychological Examination-2. Primary outcome: proliferation of ONE cells from schizophrenic patients at passage 3. Secondary outcome: association between alteration of cell proliferation and cognitive function.
Fresh ONE cells from patients showed a faster cell proliferation than those from healthy controls at passage 3. An opposite trend was observed at passage 9, ONE cells of patients with schizophrenia showing slower cell proliferation as compared to healthy controls. In schizophrenia, overall cognitive function (Spearman’s rho -0.657, p < 0.01), verbal memory – immediate recall, with interference at 10 s and 30 s (Spearman’s rho from -0.676 to 0.697, all p < 0.01) were inversely associated with cell proliferation at passage 3.
Fresh ONE cells collected by nasal brushing might eventually represent a tool for diagnosing schizophrenia based upon markers of cell proliferation, which can be easily implemented as single-layer culture. Cell proliferation at passage 3 can be regarded as a promising proxy of cognitive functioning in schizophrenia. Future studies should replicate these findings, and may assess whether ONE alterations are there before onset of psychosis, serving as an early sign in patients with at risk mental state.
Endometrial injury is an important cause of intrauterine adhesion (IUA), amenorrhea and infertility in women, with limited effective therapies. Recently, stem cells have been used in animal experiments to repair and improve injured endometrium. To date, our understanding of adipose-derived stem cells (ADSCs) in endometrial injury repair and their further therapeutic mechanisms is incomplete. Here, we examined the benefit of ADSCs in restoration of injured endometrium by applying a rat endometrial injury model. The results revealed by immunofluorescence showed that green fluorescent protein (GFP)-labelled ADSCs can differentiate into endometrial epithelial cells in vivo. At 30 days after ADSCs transplantation, injured endometrium was significantly improved, with increased microvessel density, endometrial thickness and glands when compared with the model group. Furthermore, the fertility of rats with injured endometrium in ADSCs group was improved and had a higher conception rate (60% vs 20%, P = 0.014) compared with the control phosphate-buffered saline (PBS) group. However, there was no difference in the control group compared with the sham group. In addition, expression levels of the oestrogen receptor Eα/β (ERα, ERβ) and progesterone receptor (PR) detected by western blot and enzyme-linked immunosorbent assay (ELISA) were higher in the ADSCs group than in the PBS group. Taken together, these results suggested that ADSC transplantation could improve endometrial injury as a novel therapy for IUA.
Atomically resolved imaging of materials enabled by the advent of aberration-corrected scanning transmission electron microscopy (STEM) has become a mainstay of modern materials science. However, much of the wealth of quantitative information contained in the fine details of atomic structure or spectra remains largely unexplored. In this article, we discuss new opportunities enabled by physics-informed big data and machine learning technologies to extract physical information from static and dynamic STEM images, ranging from statistical thermodynamics of alloys to kinetics of solid-state reactions at a single defect level. The synergy of deep-learning image analytics and real-time feedback further allows harnessing beam-induced atomic and bond dynamics to enable direct atom-by-atom fabrication. Examples of direct atomic motion over mesoscopic distances, engineered doping at selected lattice sites, and assembly of multiatomic structures are reviewed. These advances position the scanning transmission electron microscope to transition from a mere imaging tool toward a complete nanoscale laboratory for exploring electronic, phonon, and quantum phenomena in atomically engineered structures.
Research into the development of stem cell-derived (SCD) gametes in humans, otherwise known as in vitro gametogenesis (IVG), is largely motivated by reproductive aims. Especially, the goal of establishing genetic parenthood by means of SCD-gametes is considered an important aim. However, like other applications in the field of assisted reproduction, this technology evokes worries about the possibility of creating so-called ‘designer babies.’ In this paper, we investigate various ways in which SCD-gametes could be used to create such preference-matched offspring, and what this would mean for the acceptability of IVG, if it is premised that it is morally problematic to ‘design’ offspring. We argue that IVG might facilitate the creation of preference-matched offspring, but conclude that this should not undermine the moral acceptability of IVG altogether—even if one concedes the premise that creating ‘designer babies’ is morally problematic. In the light of this, we also point at a possible inconsistency for a position that condemns the creation of ‘designer offspring,’ while accepting the various endeavors to have genetically related offspring.