ARTICLE | doi:10.20944/preprints202108.0305.v1
Subject: Keywords: ethics of technology; emerging technologies; disruptive technology; systemic disruption; ethics of disruption
Online: 13 August 2021 (22:53:28 CEST)
Disruptive technologies can be conceptualized in different ways. Depending on how they are conceptualized, different ethical issues come into play. This article contributes to a general framework to navigate the ethics of disruptive technologies. It proposes three basic distinctions to be included in such a framework. First, emerging technologies may instigate localized “first-order” disruptions, or systemic “second-order” disruptions. The ethical significance of these disruptions differs: first-order disruptions tend to be of modest ethical significance, whereas second-order disruptions are highly significant. Secondly, technologies may be classified as disruptive based on their technological features or based on their societal impact. Depending on which of these classifications one adopts and takes as the starting point of ethical inquiry, different ethical questions are foregrounded. Thirdly, the ethics of disruptive technology raises concerns at four different levels of technology assessment: the technology level, the artifact level, the application level, and the society level. The respective suitability of approaches in technology ethics to address concerns about disruptive technologies co-varies with the respective level of analysis. The article clarifies these distinctions, thereby laying some of the groundwork for an ethical framework tailored for assessing disruptive technologies.
ARTICLE | doi:10.20944/preprints202212.0015.v1
Subject: Social Sciences, Economics Keywords: Fintech; disruption; transformation; bibliometric analysis
Online: 1 December 2022 (08:09:39 CET)
The present-day financial system is being influenced by the rapid development of Fintech (financial technologies), which are technologies created to improve and automate traditional forms of finance for businesses and consumers. The topic of Fintech as a financial disruptor is gaining popularity in line with the swift spread of digitalization across the banking industry, whereby this paper contributes to the field by presenting a novel bibliometric analysis of academic literature related to Fintech as a financial disruptor. The analysis is based on metadata extracted from the Scopus database through the VOSviewer and Biblioshiny software. The bibliometric analysis of 363 documents identified the most impactful sources of publication, keywords, authors, and most cited documents on the topic of Fintech as a financial disruptor. As our analysis demonstrates the number of publications on the given topic increases, defining both the interest among academia and potential for future research.
ARTICLE | doi:10.20944/preprints202110.0085.v1
Subject: Social Sciences, Law Keywords: Artificial intelligence; Legal research; Disruption; Legal AI tools
Online: 5 October 2021 (13:04:06 CEST)
Legal research is an indispensable skill for lawyers. Therefore, it is always necessary for lawyers to engage in legal research in due course of trying to alleviate various legal problems. Although the purpose and methodology of the research may vary from lawyer to lawyer, doing research is a common activity. As a result, the quest to assess the impacts of artificial intelligence (hereinafter ‘AI’) on legal research allows one to measure the influence of AI on the legal profession in general. Moreover, with the advent of Legal AI, it is now evident that the legal profession is not immune from disruption. According to the above, this article discusses the impacts of AI on research in the legal profession in general in accomplishing various lawyerly tasks by different legal professionals.
COMMUNICATION | doi:10.20944/preprints202106.0364.v1
Subject: Medicine & Pharmacology, Other Keywords: Diabetic foot infection; biofilm disruption; Kirschner wire; sonication
Online: 14 June 2021 (13:25:16 CEST)
Background: Diabetic foot infection (DFI) is the commonest diabetic problem requiring hospital admission. Culture yield can be challenging, particularly in the presence of biofilms. Literature confirms biofilms are ubiquitous in diabetic foot ulcer, although, there is not a microbiologic diagnostic approach regarding biofilm disruption on DFI. We postulated sonicating a stainless-steel wire along with tissue samples into the thioglycollate broth media (TBM) may improve the diagnosis of DFI. Method: Pro-spective unicentric study that assessed patients with DFI who underwent surgical debridement. The vascular surgery team collected tissue fragments and inoculated the specimens into three TBM to execute the conventional culture method (CCM), and ad-ditional fragments to place into other TBM along with a Kirschner wire (K-wire – Kw method). The microbiologist processed the samples and the resultant sonication fluid in aerobic sheep-blood agar after 24 hours, 5 and 10 days of incubation. Both methods were compared (Wilcoxon test; p < 0.05). Results: The number of pathogens isolated in each method was not statistically significant (p = 0.414): CM = 1.67 (± 0.92); KwM = 1.75 (± 0.94). The KwM was not inferior to CCM. In addition, despite the absence of statistical significance, the KwM detected more pathogens than CCM.
REVIEW | doi:10.20944/preprints202210.0230.v1
Subject: Life Sciences, Molecular Biology Keywords: PBDE; dose-response relationships; mTOR signaling; steroidogenesis; metabolic disruption; sperm epigenome
Online: 17 October 2022 (05:37:53 CEST)
Polybrominated diphenyl ethers (PBDE) are a group of flame retardants used in a variety of artificial materials. Despite phasing out in most industrial countries, they persist in the environment and human tissues due to their persistence, lipophilicity, and bioaccumulation. Populational and experimental studies demonstrate male reproductive toxicity of PBDEs including increased incidence of genital malformations (hypospadias and cryptorchidism), altered weight of testes and other reproductive tissues, altered testes histology and transcriptome, decreased sperm production and sperm quality, altered epigenetic regulation of developmental genes in spermatozoa and altered secretion of reproductive hormones. A broad range of mechanistic hypotheses of PBDE reproductive toxicity has been suggested. Among these hypotheses, oxidative stress, disruption of estrogenic signaling, and mitochondria disruption are affected by PBDE concentrations much higher, than concentrations found in human tissues, making them unlikely links between exposures and adverse reproductive outcomes in the general population. Robust evidence suggests that at environmentally relevant doses, PBDEs and their metabolites may affect male reproductive health via mechanisms including AR antagonism and the disruption of a complex network of metabolic signaling.
REVIEW | doi:10.20944/preprints202108.0383.v1
Subject: Chemistry, Analytical Chemistry Keywords: Bacterial carotenoids; Cell disruption; HPLC separation; MS analysis; Food and textile applications
Online: 18 August 2021 (14:09:35 CEST)
Natural carotenoids are secondary metabolites that exhibit antioxidant, anti-inflammatory and anti-cancer properties. These types of compounds are in high demand by pharmaceutical, cosmetic, textile and food industries, leading to the search for new natural sources of carotenoids. In recent years, the production of carotenoids from bacteria has become of great interest for industrial applications. In addition to carotenoids with C40-skeletons, some bacteria have the ability to synthesize characteristic carotenoids with C30-skeletons. In this regard, a great variety of methodologies for the extraction and identification of bacterial carotenoids has been reported and this is the first review that condenses much of this information. To understand the diversity of these carotenoids, we present their biosynthetic origin in order to focus on the methodologies employed in their extraction and characterization. Special emphasis has been made on high-performance liquid chromatography-mass spectrometry (HPLC-MS) for the analysis and identification of bacterial carotenoids. We end up this review showing their potential commercial use of bacterial carotenoids. This review is proposed as a guide for the identification of these metabolites, which are frequently reported in new bacteria strains.
Subject: Life Sciences, Cell & Developmental Biology Keywords: Prostaglandin D2; BW245c; prostanoid signalling; EP4 receptor; endothelial barrier; barrier disruption; microvascular endothelium
Online: 12 June 2020 (05:05:37 CEST)
Life-threatening inflammatory conditions such as acute respiratory distress syndrome or sepsis often go hand in hand with severe vascular leakage. During inflammation, endothelial cell integrity and intact barrier function are crucial to limit leukocyte and plasma extravasation. Prostaglandin D2 (PGD2) is a potent inflammatory lipid mediator with vasoactive properties. It has been suggested that PGD2 is involved in the regulation of endothelial barrier function; however, it is unclear whether this is also true for primary human pulmonary microvascular endothelial cells. Furthermore, as PGD2 is a highly promiscuous ligand, we set out to determine which receptors are important in human pulmonary endothelial cells. In the current study, we found that PGD2 and the DP1 agonist BW245c potently strengthened pulmonary and dermal microvascular endothelial cell barrier function and protected against thrombin-induced barrier disruption. Yet surprisingly, these effects were mediated only to a negligible extent via DP1 receptor activation. In contrast, we observed that the EP4 receptor was most important and mediated the barrier enhancement by PGD2 and BW245c. These data demonstrate a novel mechanism by which PGD2 may modulate inflammation and emphasizes the role of EP4 receptors in human endothelial cell function.
REVIEW | doi:10.20944/preprints202005.0411.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Clinical Trials; disruption; non-COVID-19 clinical trials; drugs; therapeutic area
Online: 25 May 2020 (11:17:56 CEST)
COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.
ARTICLE | doi:10.20944/preprints202208.0244.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Traumatic brain injury; buprenorphine; Bup-SR-Lab; microglia; astrocyte; myelin, membrane disruption; somatosensory sensitivity
Online: 12 August 2022 (13:52:14 CEST)
Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manor 4w following diffuse brain injury.
REVIEW | doi:10.20944/preprints201807.0008.v1
Subject: Life Sciences, Biophysics Keywords: antimicrobial peptides; cell-penetrating peptides; biophysical characterization; uptake mechanism; membrane disruption; peptide-lipid interactions
Online: 2 July 2018 (10:37:22 CEST)
In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide–membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.
ARTICLE | doi:10.20944/preprints202103.0258.v1
Subject: Life Sciences, Biochemistry Keywords: Antivirals; peptoids; LL-37; air-liquid interface; cytotoxicity; membrane disruption; COVID-19; HSV-1; SARS-CoV-2
Online: 9 March 2021 (10:25:03 CET)
Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. This suggests a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents.
CONCEPT PAPER | doi:10.20944/preprints201811.0599.v1
Subject: Social Sciences, Geography Keywords: geographies of disruption; data analytics; policy intervention; Uber; disruptive technology; disruptive innovation; path dependency; platform development; platform economics
Online: 27 November 2018 (06:52:38 CET)
The topic of technology development and its disruptive effects has been the subject of much debate over the last 20 years with numerous theories at both macro and micro scale offering potential models of technology progression and disruption. This paper focuses on how the potential theories of technology progression can be integrated and considers whether suitable indicators of this progression and any subsequent disruptive effects (particularly considering these geographically) might be derived, based on the use of big data analytic techniques. Given the magnitude of the economic, social and political implications of many disruptive technologies, the ability to quantify disruptive change at the earliest possible stage could deliver major returns by reducing uncertainty, assisting public policy intervention and managing the technology transition through disruption into deployment. However, determining when this stage has been reached is problematic because small random effects in the timing, direction of development, the availability of essential supportive technologies or “platform” technologies, market response or government policy can all result in failure of a technology, its form of adoption or optimality of implementation. This paper reviews some of the key models of technology evolution and their disruptive effect including, in particular, the geographical spread of disruption. It suggests a methodology for utilising the recent explosion of open and web-discoverable data to determine a methodology to achieve this earlier determination and considers the potential exploitation of big data modelling and predictive analytical techniques to achieve this goal.