Transnational Political Regulation of Bitcoin

Virtual currencies have recently emerged at the intersection of Internet and finance, bringing unprecedented innovations in payment systems, money and finance. In particular, Bitcoin is examined as the first example of virtual currency, dating back to 2009. Ever since virtual currencies emerged, they received increased attention from public, private and societal regulators, especially in the field of finance. Since regulation of Bitcoin is still in its infancy, this project will rather aim to unpack the underlying rationalities of power. Employing the concept of governmentality, this thesis performs Critical Discourse Analysis on policy papers, statements and press releases from public, private and societal regulators of finance. Rationalities of power and regulation are unpacked along three categories: ideas over the object that has to be regulated; ideas over the objectives that regulation has to achieve; ideas over the technical tools to be employed to achieve said aims. The results envision a future in which regulation will be public, transnational and permissive. The attitude of regulators is aimed at co-opetition, understood as a mix of competition and co-optation of virtual currencies in the current paradigm of regulation of money and finance. The future scenario will be mostly decided by strategic employment of material and institutional power by public and private actors in order either to limit or to support the adoption and diffusion of virtual currencies. However, it seems unlikely that virtual currencies will simply vanish in the future

Laterality: Motor Learning & the Non-Dominant Hand

The cultural design of the United States of America has caught up its left-handed individuals in a righthander\u27s world. Daily the left-hander or sinistral is forced to cope with problems which present themselves only to sinistrals, posing no difficulty to right-handers or dextrals. It was the intention of this investigation to determine whether, as a result of this emphasis on dextrality training, sinistrals could more quickly learn motor tasks with the non -dominant hand than could dextrals. The hypothesis upon which the investigation was founded was stated in null form: no significant difference exists between motor learning displayed by sinistrals as compared to dextrals in performing a novel motor task with the non-dominant hand. The experimental design of the investigation was that of two group, multiple experimental sessions. The subjects were volunteers from the spring semester 1977 physical education classes at Western Kentucky University. The twelve subjects participating in the experiment were female, non-physical education majors between the ages of eighteen and twenty-one. Six of the subjects made up the right-hand dominant sample, the remaining six subjects made up the left-hand dominant sample. Subjects were required to complete twelve experimental sessions within a four week period. At each session each subject performed the experimental task of juggling two tennis balls in the non-dominant hand for two periods of three minutes. These performances were scored using the dichotomous factors of catches and trials. The data collected from the experiment were analyzed by using an analysis of covariance test to ascertain levels of significance reached by each sample group for the factors of catches and trials. An analysis of covariance test was also used to ascertain the levels of significance reached by the twelve sample subjects taken as one group, for the factors of catches and trials. Finally, an analysis of covariance test was used to ascertain whether either sample group learned significantly more than the other group for the factors of catches and trials. It was found that both sample groups reached significant levels of learning for the factor of catches; however, only the right-hand dominant sample reached significance for the factor of trials. The twelve sample subjects, taken as one group, reached significant levels of learning for the factor of catches, but not trials. Finally, neither sample group learned significantly more than the other group for the factors of catches and trials. The analyses of data of this investigation resulted in a failure to reject the hypothesis. Three possible explanations for this failure to reject the hypothesis were advanced: 1) Conditioning of sinistrals to negative self-images, resulting in psychological attitude negatively effecting motor performance. 2) The sample sinistrals, eighteen to twenty-one years of age, did not suffer the process of conversion to dextrality training that sinistrals of previous decades suffered. 3) The theories of the generality of transfer versus the specificity of transfer of motor skills

Chemical Synthesis of the Thymocyte Differentiation Antigen 1 (Thy-1) N-glycoprotein

The glycosylation of the proteins is a common post-translational modification found in eukaryotic cells. Glycosylated proteins play a crucial role in cell adhesion, cell-matrix interaction, and immune response. Several studies suggest that the overexpression of these glycoconjugates is linked to many diseases, inflammation, viral infections, cancer metastasis, and cellular apoptosis among other pathologies. Over the years, the scientific community has tried to answer questions about the influence of the oligosaccharides on the protein structure or the relationship between the oligosaccharide structure and glycoproteins function. The main limitation to study these important aspects is the difficulty to obtain homogeneous isoforms of glycoproteins due to the lack of genetic control in the biosynthesis. The crescent interest in the understanding of structure-activity relationship of glycoproteins has led to the development of new technologies to obtain complex glycans and proteins. In this work, different methodologies were investigated to synthesize defined isoforms of the ubiquitous glycoprotein called Thy-1 or CD90. This heavily glycosylated protein was first discovered in 1964 in mouse T lymphocytes and later detected in human fibroblast neurons, blood stem cells, and endothelial cells. The 25kDa glycoprotein is translated as a 161 and 160 amino acids length protein in humans and mouse, respectively. The protein is transferred from ribosomes into the ER and receives several post-translational modifications including N-glycosylation at three different asparagine residues and a glypiation at the C-terminal cysteine residue. Several studies showed the association between the expression of Thy-1 and T cell activation, neurite outgrowth, apoptosis, leukocyte and melanoma cell adhesion and migration, tumor suppression, and fibroblast proliferation. The exploration of the structure-activity relationship to determine the role of the glycosylation on this protein required defined glycoprotein and motivated this work to develop a de novo synthesis of the Thy-1 pure glycoforms. The retrosynthesis of the mature glycoprotein was designed considering three key steps: 1) the assembly of the primary sequence of the protein; 2) the introduction of glycans into the protein; 3) the differentiation of the oligosaccharides at the glycosylation sites. The primary sequence of the glycoprotein was obtained using a sequential native chemical ligation (NCL) of three segments: the peptide fragment (1-18), the glycopeptide (19-84) having two N glycosylations, and the glycopeptide (85-110) containing one N glycosylation. The three peptide fragments were synthesized by solid-phase peptide synthesis (SPPS) and were obtained having a hydrazide moiety on the C-terminus that was converted into a thioester prior to the NCL. For this purpose, a Wang and a trityl resin were functionalized with hydrazine and modified manually with the amino acid on the C-termini. The protecting acetamidomethyl group was used to mask the thiol of the N-terminal cysteine residues in the fragment (19-84) and (85-110) to allow the stepwise ligation of the fragments. The elongation of the polypeptide chains was carried out in the microwave-assisted synthesizer and careful optimization of deprotection and coupling cycles was executed for the three fragments. The incorporation of amino acids was performed considering the common problems that affect the peptide synthesis including the cyclization reaction on asparagine and aspartic acid, and the racemization of cysteine and histidine at temperatures higher than 50°C. These precautions were not enough to obtain the Thy-1 glycopeptide fragments in high yield and with desired quality. The synthesis of the designed peptides required multiple optimizations to avoid side reactions. Some general requirements were established. Hindered amino acids (glutamic acid, isoleucine, and phenylalanine) required double coupling to assure complete attachment to the growing chain. Vicinal identical amino acids (e.g. serine 25-serine 26) were introduced using single coupling for the first residue in the sequence and a double coupling for the following residue. One of the most crucial point for the optimization of the synthesis was the minimization of the aspartimide formation involving the cyclization of the aspartic acid. Among different cocktails for the removal of the Fmoc group promising the suppression of this side reaction, the best results were obtained by using 20% piperidine and 0.7% of formic acid in dimethylformamide, which reduced the aspartimide formation up to 70%. The glycosylations were introduced following two approaches to allow differentiation between the glycan at each glycosylation site. In the cassette-method, a glycosylated asparagine was synthesized and incorporated in the corresponding glycosylation site during the assembly of the peptides. Different procedures were evaluated and optimized for the synthesis of the N-acetyl-O-per-acetylated glucosaminyl asparagine 2 and its introduction into SPPS to get the fragments 6a-c (19-84) and 37a-b (85-110) with a peracetylated glucosamine on each glycosylation site. The convergent approach was used to synthesize fragment 6b (19-84) having the peracetylated N acetylglucosamine 2 in one glycosylation site and an unprotected N-acetylglucosamine, installed via Lansbury aspartylation on the second site. The Lansbury strategy required the formation of the amide bond between the free carboxylate at an aspartic acid and the N-acetylglucosamine amine. The reaction was performed on the fully protected peptide fragment and required the synthesis of two building blocks, an orthogonal protected aspartic acid 3, and a pseudoproline dipeptide 4. The aspartic acid was synthesized with a photolabile protecting group on the side chain, which was selectively removed on resin to give a free carboxylic acid. To avoid the undesired rearrangement of the amino acid, the protected pseudoproline dipeptide Thr-Ser(Me,MePro) was incorporated before the aspartic acid. The three (glyco)peptides were efficiently synthesized by a combination of manual and automated processes and were characterized by their challenging purifications. The difficulties in obtaining the isoforms from the Thy-1 fragment (19-84) glycopeptides 6a-b, were related to the low solubility of the generated glycopeptides and the loss of acetyl groups on the peracetylated glucosamine. The analysis of these problems led to the design of the optimal strategy to synthesize in high yield the fragment 6c having a protected and non-protected N‑acetylglucosamine. The synthesis of glycoform 6c involved the coupling of a per-acetylated N-acetylglucosaminyl asparagine building block in the peptide sequence that was de-acetylated before the introduction of the second glycosylated asparagine residue. The assembly of the Thy-1 glycoprotein involved the ligation of the synthesized fragments by the chemoselective reaction between the C-terminal peptide thioester in one peptide fragment and the free N-terminal cysteine residue of another fragment. The process required the conversion of the synthesized peptide hydrazides into the corresponding thioesters prior to each ligation and the removal of the Acm-group of the fragments having the N-terminal cysteine. Two combinations were studied to ligate the three fragments: from C- to N-terminus and from N- to the C-terminus. The first approach consisted of the initial ligation of the glycopeptides 6a-c (19-84) and 37a-b (85-110) and the subsequent ligation with the peptide 1 (1-18). The second strategy involved the reaction of peptide 1 (1-18) with the glycopeptide 6a-c (19-84) and the following ligation with the fragment 37a-b (85-110). The ligation conditions were investigated, and the strategy was selected considering factors such as the availability and solubility of the fragments, number of steps and the efficiency of the processes. The N-to C-strategy was the first approach adopted. The hydrazide precursor 6a was converted into the thioester fragment 38 by formation of the peptide azide at low pH and thiolysis with the corresponding thiol. The Acm group from the cysteine in 37b was removed with mercury (II) acetate and reduction of the sulfur-mercury complex with mercaptoethanol. The ligation of the fragments delivered the glycoprotein 40 and the hydrolysed fragment 38 as by-product. The low solubility of the glycoprotein 40 hampered the isolation of the product and suggested the need of more polar fragment. For this purpose, glycoform 6b was converted into the thioester 41 and reacted with fragment 37a having a free N-terminal cysteine. Surprisingly, this ligation did not proceed suggesting that the treatment with mercury (II) acetate could be beneficial for the ligation. A N- to C- ligation of fragment 6c treated with the mercury (II) acetate with the thioester of fragment 1 proceeded successfully and the isolation of the ligation product yielded the glycoprotein 45, confirming the better behaviour of polar fragments and reactivity of the cysteine-containing fragments treated with mercury. A ligation of the MPAA thioester of Thy-1 fragment (1-84) with 37b to obtain the full glycoprotein Thy-1 (1-120) was hindered by the poor solubility of thioester 46 in the ligation media. A new C- to N- ligation involving the polar glycoform 6c with the fragment 37b delivered the glycoprotein 49 that was treated in one-pot with PdCl2 to release the N-terminal cysteine and get 50. Finally, a methyl 3-mercaptopropionate MMP thioester of fragment 1-18 (51) was ligated with glycoprotein fragment 50 to obtain the desired Thy-1 glycoprotein (1-120) having three glycosylations. In this work was presented the design and evaluation of different strategies for the synthesis of the glycoprotein Thy-1. The assembly of the 13kDa glycoprotein required different steps and the optimized synthesis of amino acid building blocks for the solid-phase assembly of glycopeptides. Various methods were applied for the generation of glycopeptides, the exploration of the chemical properties of the obtained fragments, and the modulation of the chemical conditions for the ligation of the peptide fragments to get the target glycoprotein. This work focused on the production of homogeneous glycoforms of Thy-1. However, the synthetic methods and protocols established in this work are applicable for the synthesis of any peptides and glycopeptides and contribute to the chemical synthesis of other important glycoproteins

Types of phonological processes occurring in normal Black English speakers

Black English (BE) is a rule-governed linguistic system with its own phonology, syntax, semantics, and pragmatics. BE is a dialect, not a disordered variation of standard English (SE). When compared to SE, BE phonology has been described in terms of omissions, substitutions, and additions. This study looked at normal BE speakers in Portland, Oregon and described their dialectal differences in terms of phonological processes

Strengthening Advising Knowledge to Improve Consistency and Coordination in Academic Advising

This Organizational Improvement Plan (OIP) aims to improve consistent and coordinated academic advising at a medium, multi-campus higher education institution (HEI). It recognizes the vital role of academic advising in supporting a student’s academic journey. The OIP delves deeper into the responsibilities of HEI leaders with regard to facilitating the capacity of academic advisors to support students in their academic and personal growth and development. The present state of affairs suggests that academic advisors are not positioned to support and facilitate a student’s growth and development. The OIP seeks to gain a comprehensive understanding of the underlying factors contributing to the issue by providing a historical overview and reviewing academic advising literature, wider contextual factors, and organizational theories. The OIP proposes utilizing adaptive and systems thinking leadership as the primary leadership approaches to lead the proposed change. Integrating various approaches can strengthen one another and address gaps, enabling change leaders to identify the issue and comprehend its interconnectedness more precisely. The problem is framed using the political and systems perspectives. Understanding resistance plays a vital role in this OIP. Therefore, Kotter’s Eight Step Change Model is utilized to lead the change process, and the Krüger Model of Change Management is utilized to ensure that the human element of the change process is not overlooked. The change recommended in this OIP is multifaceted and complex. The goal is to transform advising practices and develop institutional accountability and responsibility to students and advisors through the implementation of a training program

Close to the metal: Towards a material political economy of the epistemology of computation

This paper investigates the role of the materiality of computation in two domains: blockchain technologies and artificial intelligence (AI). Although historically designed as parallel computing accelerators for image rendering and videogames, graphics processing units (GPUs) have been instrumental in the explosion of both cryptoasset mining and machine learning models. The political economy associated with video games and Bitcoin and Ethereum mining provided a staggering growth in performance and energy efficiency and this, in turn, fostered a change in the epistemological understanding of AI: from rules-based or symbolic AI towards the matrix multiplications underpinning connectionism, machine learning and neural nets. Combining a material political economy of markets with a material epistemology of science, the article shows that there is no clear-cut division between software and hardware, between instructions and tools, and between frameworks of thought and the material and economic conditions of possibility of thought itself. As the microchip shortage and the growing geopolitical relevance of the hardware and semiconductor supply chain come to the fore, the paper invites social scientists to engage more closely with the materialities and hardware architectures of ‘virtual’ algorithms and software

GSTP1 Polymorphisms Sex-Specific Association with Cognitive Outcomes in Survivors of Pediatric Medulloblastoma Tumors

This study investigated specific single nucleotide polymorphisms (SNPs) and their association with attentional deficits and hippocampal volume in survivors of medulloblastoma brain tumors. The sample with neuropsychological assessment includes eighteen medulloblastoma survivors and eighteen age-and-sex-matched healthy controls. We hypothesized that medulloblastoma survivors with a GSTP1 polymorphism will have significantly greater deficits in attention span and smaller bilateral hippocampal volumes compared to survivors without a polymorphism and healthy controls. We did not establish the specificity of hippocampal volume loss, and our sample may have more global subcortical morphological alterations. When separating groups by sex, we found large effect sizes between males with a GSTP1 polymorphism and females with a GSTP1 polymorphism across measures of attention span, working memory span and processing speed. Females with a polymorphism performed significantly worse than females without a polymorphism on full-scale intelligence quotient (IQ) and verbal IQ. Sex-specific genetic risk may explain part of the variability in long-term cognitive outcomes for medulloblastoma survivors