LLukas22/scidocs huggingface dataset:
Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial

BACKGROUND
Parkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease.


METHODS
We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. All patients were then enrolled in a separate open-label follow-up study of long-term safety. Three doses were assessed in separate cohorts: low dose (1·9×10(7) transducing units [TU]); mid dose (4·0×10(7) TU); and high dose (1×10(8) TU). Inclusion criteria were age 48-65 years, disease duration 5 years or longer, motor fluctuations, and 50% or higher motor response to oral dopaminergic therapy. The primary endpoints of the phase 1/2 study were the number and severity of adverse events associated with ProSavin and motor responses as assessed with Unified Parkinson's Disease Rating Scale (UPDRS) part III (off medication) scores, at 6 months after vector administration. Both trials are registered at ClinicalTrials.gov, NCT00627588 and NCT01856439.


FINDINGS
15 patients received ProSavin and were followed up (three at low dose, six mid dose, six high dose). During the first 12 months of follow-up, 54 drug-related adverse events were reported (51 mild, three moderate). Most common were increased on-medication dyskinesias (20 events, 11 patients) and on-off phenomena (12 events, nine patients). No serious adverse events related to the study drug or surgical procedure were reported. A significant improvement in mean UPDRS part III motor scores off medication was recorded in all patients at 6 months (mean score 38 [SD 9] vs 26 [8], n=15, p=0·0001) and 12 months (38 vs 27 [8]; n=15, p=0·0001) compared with baseline.


INTERPRETATION
ProSavin was safe and well tolerated in patients with advanced Parkinson's disease. Improvement in motor behaviour was observed in all patients.


FUNDING
Oxford BioMedica.
Distalization pattern of the maxillary arch depending on the number of orthodontic miniscrews.

OBJECTIVE
To determine the effects of linear force vector(s) from interradicular miniscrews on the distalization pattern of the maxillary arch in adult Class II patients.


MATERIALS AND METHODS
Twenty-five adult patients with mild to moderate Class II dentition and minimal crowding were collected. Either single (group A, n  =  12) or dual (group B, n  =  13) miniscrews were inserted on the posterior interradicular area to deliver a distalizing force to the main archwire. The displacement patterns of maxillary incisors and molars were measured and compared.


RESULTS
  Significant distalization in the molars and incisors was shown in both groups. Significantly greater distalization and intrusion of the first molar and intrusive displacement of the incisor, together with significant reduction of the mandibular plane, were noted in group B, in contrast to the rotation of the occlusal plane in group A.


CONCLUSIONS
Interradicular miniscrews predictably induced total arch distalization, leading to the correction of Class II. Additional miniscrews in the premolar area appear to facilitate intrusion and distalization of the entire arch according to the position of the force vectors.
On Enlightenment’s margins: geography, imperialism and mapping in Central Asia, c.1798–c.1838

Abstract This paper examines the nature of British geographical work in Central Asia (Persia and Afghanistan) in a period when Britain was concerned about a region which lay between Europe and Enlightenment on the one hand, and her Indian colonies, the uncertainties of Asia and the imperial designs of France and Russia on the other. The paper explores the connections between geography, diplomacy and colonial knowledge and demonstrates how the mapping and geographical study of Central Asia was a central feature of British colonial ambitions and of Enlightenment conceptual reasoning. In illuminating the ways in which ‘ancient’ and ‘modern’ geography was at work in this politically core yet geographically ‘marginal’ space, the paper highlights the complexities intrinsic to the making of geography and of empire in a region until now neglected in modern historical geography.
Advanced Adhesives based on Carbon Nanotube Technology

For microsystems packaging and system integration new processing techniques are being developed on the basis of advanced composites using nanoscale building blocks - here carbon nanotubes - incorporated in relevant interconnect materials, such as metallic solders and highly conductive polymer based adhesives.
Tracking via object reflectance using a hyperspectral video camera

Recent advances in electronics and sensor design have enabled the development of a hyperspectral video camera that can capture hyperspectral datacubes at near video rates. The sensor offers the potential for novel and robust methods for surveillance by combining methods from computer vision and hyperspectral image analysis. Here, we focus on the problem of tracking objects through challenging conditions, such as rapid illumination and pose changes, occlusions, and in the presence of confusers. A new framework that incorporates radiative transfer theory to estimate object reflectance and the mean shift algorithm to simultaneously track the object based on its reflectance spectra is proposed. The combination of spectral detection and motion prediction enables the tracker to be robust against abrupt motions, and facilitate fast convergence of the mean shift tracker. In addition, the system achieves good computational efficiency by using random projection to reduce spectral dimension. The tracker has been evaluated on real hyperspectral video data.
Shape Control of Colloidal Metal Nanocrystals

reviews P. Yang et al. Colloidal metal nanoparticles are emerging as key materials for catalysis, plasmonics, sensing, and spectroscopy. Within these applications, control of nanoparticle shape lends increasing functionality and selectivity. Shape-controlled nanocrystals possess well-defined surfaces and morphologies because their nucleation and growth are controlled at the atomic level. An overall picture of shaped metal particles is presented, with a particular focus on solution-based syntheses for the noble metals. General strategies for synthetic control are discussed, emphasizing key factors that result in anisotropic, nonspherical growth such as crystallographically selective adsorbates and seeding processes.
Automatic Parallelization of Arbitrary Programs

We describe the latest version of the Paragen system, a tool for the automatic transformation of serial programs into functionally identical parallel ones. Previous papers on this work have described means of converting either sequences of instructions or individual loops, and here we describe how the two tasks can be melded into a single, seamless operation.
Advances in the treatment of chronic heart failure.

I United States Agency for International Development. Breastfeeding: a report on AID programs. Washington, DC: US Agency for International Development, 1990. 2 De Zoysa I, Rea M, Martines J. Why promote breastfeeding in diarrhoeal disease control programmes? Health Policy and Planning 1991;6:371-9. 3 Brown KH, Stallings RY, Creed de Kanashiro H, Lopez de Romana G, Black RE. Effects of common illnesses on infants' energy intakes from breast milk and other foods during longitudinal community-based studies in Huascar (Lima), Peru. Am J Clin Nunr 1990;52:1005-13. 4 Popkin BM, Adair L, Akin JS, Black R, Briscoe J, Flieger W. Breast-feeding and diarrheal morbidity. Pediatrics 1990;86:874-82. 5 Victora CG, Smith PG, Vaughan JP, Nobre LC, Lombardi C, Teixeira AMB, et al. Infant feeding and deaths due to diarrhea: a case-control study. AmJ7 Epidemiol 1989;129:1032-41. 6 Sachdev HPS, Krishna J, Purn RK, Satyanarayana L, Kumar S. Water supplementation in exclusively breastfed infants during summer in the tropics. Lancet 1991;337:929-33. 7 Martines JC, Ashworth A, Kirkwood, B. Breast-feeding among the urban poor in southern Brazil: reasons for termination in the first 6 months of life. Bull World Health Organ 1989;67:151-61. 8 Akre J, ed. Infant feeding: the physiological basis. Bull World Health Organ 1989;67(suppl): 1-108. 9 Almroth SG. Water requirements of breastfed infants in a hot climate. Am J Clin Nutr 1978;31: 1154-7. 10 Armelini PA, Gonzalez CF. Breastfeeding and fluid intake in a hot climate. Clin Pediatr 1979;18:424-5. 11 Goldberg NM, Adams E. Supplementary water for breast-fed babies in a hot and dry climate-not really a necessity. Arch Dis Child 1983;58:73-4. 12 Almroth S, Bidinger PD. No need for water supplementation for exclusively breast-fed infants under hot and arid conditions. Trans R Soc Trop Med Hyg 1990;84:6024. 13 Brown KH, Creed de Kanashiro H, del Aguila R, Lopez de Romana, G, Black RE. Milk consumption and hydration status of exclusively breast-fed infants in a warm climate. J7 Pediatr 1986;108:677-8. 14 Canahuati J. One country's story: the PROALMA program in Honduras. In J Gynecol Obstet 1990;31(suppl 1):17-24. 15 World Health Organisation, United Nations Children's Fund. Protecting, promoting and supporting breast-feeding: the special role ofmaternity services. Geneva: WHO, 1989.
5-HT1A receptors are involved in the effects of xaliproden on G-protein activation, neurotransmitter release and nociception.

BACKGROUND AND PURPOSE
Xaliproden (SR57746A) is a 5-HT(1A) receptor agonist and neurotrophic agent that reduces oxaliplatin-mediated neuropathy in clinical trials. The present study investigated its profile on in vitro transduction, neurochemical responses and acute nociceptive pain tests in rats.


EXPERIMENTAL APPROACH
Xaliproden was tested on models associated with 5-HT(1A) receptor activation including G-protein activation, extracellular dopamine and 5-HT levels measured by microdialysis and formalin-induced pain. Activation of 5-HT(1A) receptors was confirmed by antagonism with WAY100635.


KEY RESULTS
Xaliproden exhibited high affinity for rat (r) and human (h) 5-HT(1A) receptors (pK(i)= 8.84 and 9.00). In [(35)S]GTPgammaS (guanosine 5'-O-(3-[(35)S]thio)triphosphate) assays it activated both hippocampal r5-HT(1A)[pEC(50)/E(MAX) of 7.58/61% (%5-HT)] and recombinant h5-HT(1A) receptors (glioma C6-h5-HT(1A): 7.39/62%; HeLa-h5-HT(1A): 7.24/93%). In functional [(35)S]GTPgammaS autoradiography, xaliproden induced labelling in structures enriched with 5-HT(1A) receptors (hippocampus, lateral septum, prefrontal and entorhinal cortices). Xaliproden inhibited in vivo binding of [(3)H]WAY100635 to 5-HT(1A) receptors in mouse frontal cortex and hippocampus (ID(50): 3.5 and 3.3 mg x kg(-1), p.o. respectively). In rat, it increased extracellular dopamine levels in frontal cortex and reduced hippocampal 5-HT levels (ED(50): 1.2 and 0.7 mg x kg(-1), i.p. respectively). In a rat pain model, xaliproden inhibited paw licking and elevation (ED(50): 1 and 3 mg x kg(-1), i.p. respectively) following formalin injection in the paw. All effects were reversed by pretreatment with WAY100635.


CONCLUSIONS AND IMPLICATIONS
These results indicate that activation of 5-HT(1A) receptors is the principal mechanism of action of xaliproden and provide further support for the utility of 5-HT(1A) receptor activation as an anti-nociceptive strategy.
Modelling and Simulation of Micro Hydro Power Plant Using Matlab Simulink

Micro-hydro-electric power is both an efficient and reliable form of clean source of renewable energy. It can be an excellent method of harnessing renewable energy from small rivers and streams. The micro-hydro project designed to be a run -of-river type, because it requires very little or no reservoir in order to power the turbine. The water will run straight through the turbine and back into the river or stream to use it for the other purposes. This has a minimal environmental impact on the local ecosystem. Hydro power plant mainly consists of three sections, ‘governor (controller), hydro servo system and hydro turbine’. Integrally this section is known as hydro turbine governor which is coupled to a synchronous generator to drive the shaft so that the mechanical energy of turbine is converted to the electrical energy. This system is supplying power to a common electrical three phase parallel RLC load. Models are simulated on MATLAB/Simulink. The speed governing control system ensures the constant speed operation during variation of load. The transient behavior of generator voltage, current and the rotor speed are also captured. Restoration of steady state condition within few seconds while changing the load ensures the stability of the entire system.
Eligibility and Safety of Triple Therapy for Hepatitis C: Lessons Learned from the First Experience in a Real World Setting

BACKGROUND
HCV protease inhibitors (PIs) boceprevir and telaprevir in combination with PEG-Interferon alfa and Ribavirin (P/R) is the new standard of care in the treatment of chronic HCV genotype 1 (GT1) infection. However, not every HCV GT1 infected patient is eligible for P/R/PI therapy. Furthermore phase III studies did not necessarily reflect real world as patients with advanced liver disease or comorbidities were underrepresented. The aim of our study was to analyze the eligibility and safety of P/R/PI treatment in a real world setting of a tertiary referral center.


METHODS
All consecutive HCV GT1 infected patients who were referred to our hepatitis treatment unit between June and November 2011 were included. Patients were evaluated for P/R/PI according to their individual risk/benefit ratio based on 4 factors: Treatment-associated safety concerns, chance for SVR, treatment urgency and nonmedical patient related reasons. On treatment data were analyzed until week 12.


RESULTS
208 patients were included (F3/F4 64%, mean platelet count 169/nl, 40% treatment-naïve). Treatment was not initiated in 103 patients most frequently due to safety concerns. 19 patients were treated in phase II/III trials or by local centers and a triple therapy concept was initiated at our unit in 86 patients. Hospitalization was required in 16 patients; one patient died due to a gastrointestinal infection possibly related to treatment. A platelet count of <110/nl was associated with hospitalization as well as treatment failure. Overall, 128 patients were either not eligible for therapy or experienced a treatment failure at week 12.


CONCLUSIONS
P/R/PI therapies are complex, time-consuming and sometimes dangerous in a real world setting, especially in patients with advanced liver disease. A careful patient selection plays a crucial role to improve safety of PI based therapies. A significant number of patients are not eligible for P/R/PI, emphasizing the need for alternative therapeutic options.
Modelling Symbolic Music: Beyond the Piano Roll

In this paper, we consider the problem of probabilistically modelling symbolic music data. We introduce a representation which reduces polyphonic music to a univariate categorical sequence. In this way, we are able to apply state of the art natural language processing techniques, namely the long short-term memory sequence model. The representation we employ permits arbitrary rhythmic structure, which we assume to be given. We show that our model is effective on four out of four piano roll based benchmark datasets. We further improve our model by augmenting our training data set with transpositions of the original pieces through all musical keys, thereby convincingly advancing the state of the art on these benchmark problems. We also fit models to music which is unconstrained in its rhythmic structure, discuss the properties of this model, and provide musical samples which are more sophisticated than previously possible with this class of recurrent neural network sequence models. We also provide our newly preprocessed data set of non piano-roll music data.
Optimization of machining techniques — A retrospective and literature review

In this paper an attempt is made to review the literature on optimizing machining parameters in turning processes. Various conventional techniques employed for machining optimization include geometric programming, geometric plus linear programming, goal programming, sequential unconstrained minimization technique, dynamic programming etc. The latest techniques for optimization include fuzzy logic, scatter search technique, genetic algorithm, Taguchi technique and response surface methodology.
High-frequency interleaved three-phase inverter with novel single reference six pulse modulation (SRSPM) technique

This paper presents a hybrid modulation technique consisting of singe-reference six-pulse-modulation (SRSPM) for front-end dc/dc converter and 33% modulation for three-phase inverter. Employing proposed novel SRSPM by front-end dc/dc converter, high frequency (HF) pulsating dc voltage waveform is produced, which is equivalent to six-pulse output at 6× line frequency (rectified 6-pulse output of balanced three-phase ac waveforms) once averaged. It reduces the control complexity owing to single-reference three-phase modulation as compared to conventional three-reference three-phase SPWM. In addition, it relives the need of dc link capacitor reducing the cost and volume. Eliminating dc link capacitor helps in retaining the modulated information at the input of three-phase inverter. It needs only 33% (1/3rd) modulation of the inverter devices to generate balanced three-phase voltage waveforms resulting in significant saving in (at least 66%) switching losses of inverter semiconductor devices. At any instant of line cycle, only two switches are required to switch at HF and remaining switches retains their unique state of either ON or OFF. Besides, inverter devices are not commutated when current through them is at its peak value. Drop in switching loss accounts to be around 86.6% in comparison with a standard voltage source inverter (VSI) employing standard three-phase sine pulse width modulation (SPWM). This paper explains operation and analysis of the HF two-stage inverter modulated by proposed novel modulation scheme. Analysis has been verified by simulation results using PSIM9.0.4. Experimental results demonstrate effectiveness of the proposed modulation.
Education, philosophy and politics : the selected works of Michael A. Peters

Introduction. Educational Philosophy and Politics 1. Philosophy as Pedagogy: Wittgenstein's Styles of Thinking 2. Writing the Self: Wittgenstein, Confession and Pedagogy 3. Nietzsche, Nihilism and the Critique of Modernity: Post-Nietzschean Philosophy of Education 4. Heidegger, Education and Modernity 5. Truth-Telling as an Educational Practice of the Self: Foucault, Parrhesia and the Ethics of Subjectivity 6. Neoliberal Governmentality: Foucault on the Birth of Biopolitics 7. Lyotard, Nihilism and Education 8. Gilles Deleuze's 'Societies of Control': From Disciplinary Pedagogy to Perpetual Training 9. Geophilosophy, Education and the Pedagogy of the Concept 10. Humanism, Derrida, and the New Humanities 11. Politics and Deconstruction: Derrida, Neoliberalism, and Democracy to Come 12. Ethnocentrism and the Politics of the Ethnos: Rorty's 'Postmodernist Bourgeois Liberalism' 13. Achieving America: Postmodernism and Rorty's Critique of the Cultural Left 14. Deranging the Investigations: Cavell on the Philosophy of the Child 15. White Philosophy in/of America
Why data sharing should be the expected norm.

The Institute of Medicine (IOM), a venerable American institution that seeks to provide authoritative recommendations to decision makers and the public, released a report last month on Sharing Clinical Trial Data. The report is a welcome codification of guiding principles and frameworks. It reinforces many arguments for data sharing and urges that stakeholders “should foster a culture in which data sharing is the expected norm.” The IOM joins many other organizations, including drug companies, 3 the European Medicines Agency, the National Institutes of Health, and the Bill and Melinda Gates Foundation, in making clear that study reporting and data sharing in medical research are imperative and the questions ahead are how, not whether. The general support for data sharing in the IOM document will be familiar to The BMJ’s readers, as this journal has long advocated the importance of transparency in scientific research and the need to report results and share data. The report provides what should be easily achievable recommendations for the research community. The committee called for data sharing only for new trials, though it urged consideration of sharing older studies. It stated that 18 months could elapse after the completion of a trial before investigators were asked to share. The committee also determined that sharing raw data would be too burdensome and that such data should be made available only on a case by case basis. The report states that summary level results should be publicly reported within 12 months of study completion, including lay summaries to trial participants. Further to go
Assessment of nutrients and heavy metals enrichment in surface sediments from Taihu Lake, a eutrophic shallow lake in China.

Concentrations of the nutrients (TN and TP), phosphorus fractions and heavy metals (Co, Cr, Cu, Mn, Ni, Pb, Sr, Ti, V, Zn and Hg) in 40 surface sediment samples collected from Taihu Lake, a eutrophic shallow lake in China, were determined. The results showed that the northwest region of the lake possessed higher concentrations of TN and TP, as well as the similar spatial distribution trend in the water column. This should be related to excessive anthropogenic input from industrial effluents and domestic sewage in surrounding areas. Similarly, the concentrations of P fractions exhibited significant regularity. In addition, except for Sr showing low concentration, the rest of the heavy metals in the surface sediments had two- to four-folds of magnitude of the concentrations compared with the reference values in earth's crust. In the past decade, concentrations of heavy metals had undergone different levels of variations. Principal component analysis (PCA) and enrichment factors (EFs) of the compositional data aiming at heavy metals showed that Taihu Lake was slightly exposing to heavy metal contamination except Sr. High concentrations of heavy metals were ascribed to the discharge of untreated and partially treated industrial waste water via rivers. Co, Cr, Cu, Mn, Ni, Pb, V and Zn positively correlated with each other (R = 0.78-0.92), that indicated they had analogous sources and/or kindred geochemistry characteristics. Differing from nutrients, randomness in the space indicated that heavy metals had a complex distribution.
Android and iOS users' differences concerning security and privacy

We compare Android and iOS users according to their demographic differences, security and privacy awareness, and reported behavior when installing apps. We present an exploratory study based on an online survey with more than 700 German students and describe directions for further research.