SIRIS-Lab/unlabelled-sti-corpus huggingface dataset:
Coordination in constrained and natural distributed systems

In recent years, an algorithmic theory of natural and biological systems has been increasingly advocated as providing a much needed framework for investigating complex self-organising processes in nature. This project contributes to this research program by employing the distributed computing lens to model natural phenomena. Biological systems exhibit many properties also studied in distributed computing: they comprise several independently acting entities, tend to operate in noisy and dynamic environments, thus requiring them to be highly-resilient and adaptive, solve intricate coordination tasks, and display sophisticated communication techniques.

This project aims to develop the theory of distributed synchronisation and coordination tasks in restricted models of distributed computing. These tasks are some of the most fundamental problems in distributed computing, as they are essential in computer networks as well as numerous other areas of engineering and computing. In addition, they are ubiquitous in natural and biological systems, ranging from molecular to population-level systems, which are known to solve various synchronisation and coordination tasks: examples include symmetry-breaking during the development of the nervous system, consensus decision making in species communities, and synchronisation in firefly populations and embryonic development.

Unlike computer networks, biological distributed systems have unique features: (1) the agents typically have limited computational abilities, (2) communication is unreliable and restricted, (3) the system has a dynamic spatial structure, and (4) the environment may be noisy. Currently, distributed computing models that consider all aspects simultaneously are lacking. The proposed research approaches this goal from multiple angles by developing new models and analysis methods for determining the limitations of synchronisation and related tasks in both strong and weak models of computing.
Dynamic proteomic maps of stem cell-derived neurons as a mechanistic discovery pipeline for rare neurological disease

Rare diseases are a major unmet medical need, as is the definition of the relevant disease mechanisms. Many rare diseases affect the nervous system. These are challenging to treat, and mechanistic studies are difficult due to the inaccessibility of patient tissue. Global proteomic studies have provided insight into whole tissue or cell changes in protein abundance but lose information on protein subcellular localisation, which is important because defects in protein trafficking are implicated in many neurological disorders. In ‘RARE MAPS’ I propose an unbiased mechanistic discovery pipeline combining human induced pluripotent stem cells (hiPSCs) with advanced spatial proteomics. I will use a method developed by Dr. Borner called ‘dynamic organellar maps’, which provides quantitative protein subcellular localisation information at the whole proteome level. Used comparatively, it can detect changes in protein localisation due to a perturbation, allowing unbiased screening for phenotypic changes. To develop this workflow, I will apply it to the rare neurodegenerative disorder AP-4 deficiency syndrome. AP-4 knockout hiPSCs will be differentiated into cortical neurons and maps will be made of intermediate cortical stem cells and mature cortical neurons. Comparison to control cells will enable the detection of changes to protein localisation and abundance. I will also apply the maps to brain tissue from an AP-4 deficient mouse model to detect protein mislocalisation in vivo. I will then use CRISPR/Cas9 technology to investigate the role of novel and known AP-4-associated proteins in neuronal autophagy and axonal health. This project will demonstrate the utility of dynamic organellar maps to reveal molecular mechanisms of rare neurological disorders as well as provide new insights into the pathogenesis of AP-4 deficiency and the role of protein trafficking and autophagy in the axon.
Pilot scale steam explosion and diluted sulfuric acid pretreatments: Comparative study aiming the sugarcane bagasse saccharification

Abstract Pilot-scale pretreatments, namely steam explosion (SE) and diluted sulfuric acid (SA), of sugarcane bagasse followed by alkaline delignification (SED and SAD) were explored. Most of the pentosan (97% and 93%), and the lignin content were solubilized during pretreatment and delignification process for SE and SA, respectively. SE demanded 50% more NaOH in the delignification step than SA, due to ion exchange nature of cellulignin. SE is more advantageous than SAD due to better unpacking of the fibers, allowing a higher cellulose conversion (90%) in relation to SAD pulps (79%). Cellulose conversion has a direct dependence with cellulose, hemicellulose and residual lignin. A composition factor (H*L/CC) and enzymatic kinetics were evaluated for the in natura, pretreated and pretreated and delignified materials. The Langmuir isothermal- type equation expressed a factor related to the capacity of hydrolysis, where SE pointed a material with similar hydrolysis capability of the combined SAD pretreatment.
Characterization of the molecular mechanism behind ctl - the major choline uptake system in eukaryotes

Choline is an essential nutrient necessary for the synthesis of the membrane lipids phosphatidylcholine and sphingomyelin that constitute over 50 % of the total lipid content in cellular membranes. It is the precursor for key metabolites such as the neurotransmitter acetylcholine and the osmolyte and methyl donor betaine. Transmembrane uptake of choline is the essential, but still enigmatic, first step in choline metabolism in the cell. Three groups of solute carriers have been identified in the transport of choline; CHT1, OCT and CTL (SLC5A7, SLC22, SLC44 in humans). While CHT1 and OCT perform specialized functions, the choline transporter-like (CTL) family facilitates the majority of choline uptake in all eukaryotes. Despite their clear physiological relevance, our knowledge of CTL family members is very limited, and there are no structures of choline transporters available. For this reason, knowledge on the molecular mechanism of cellular choline uptake is almost non-existent.

With this proposal, I will address this lack of data, and provide new and ground-breaking insights into the function of the CTL family members. I will elucidate the molecular mechanisms of substrate recognition and transport in the major eukaryotic choline uptake system through a combination of structural biology (X-ray crystallography and cryo-EM) and biochemical characterization. The project will focus on human CTL family members but will also include other eukaryotic CTL proteins. A structural framework on the CTL family will provide insight into a key metabolic uptake pathway present in all eukaryotes and will be a fundamental resource for further research. Furthermore, CTLs are implicated in several diseases, including cancer, and the proposed work on CTL proteins will allow for future pharmacological studies addressing these with great impact on society.
Sviluppato dal Portogallo

Questo progetto ha come base le azioni adeguatamente strutturate e sviluppate per dare alle imprese della catena Habitat della Regione Centrale condizioni di contesto sufficienti per rafforzare la loro presenza internazionale, in particolare attraverso l'esportazione verso i mercati del Messico e del Perù.
Free-wheel switching device for use in crank continuously variable transmission mechanism to change driving direction of vehicle, has switching mechanism alternatively switching between wheels, where one wheel is arranged around other wheel

The device (20) has a free-wheel (4) for common rotation of a ring (1) and an intermediate ring (2) in a direction. Another free-wheel (5) is provided for common rotation of another ring (3) and the intermediate ring in other direction, where the directions are set opposite to each other. A switching mechanism (13) alternatively switches between the former free-wheel and the latter free-wheel. The latter free-wheel is radially arranged around the former free-wheel. A bar (11) is connected with the former ring in a torque-proof manner.
Development of scalable microfluidic device for drug testing using humanized adipose tissue spheroids

In regenerative medicine, in vitro tissue engineering products (3D cell cultures) for in vivo therapy are critical for more accurate and more humane medical innovation. Tissue engineered scaffold-free 3D models that exhibit functional hallmarks of native tissues improve our search for biomarkers, drug testing/development and toxicology with more accurate models, while supporting the development of alternative methods to animal use in drug testing, as stated by the Directive (2010/63/EU) established the European Centre for the validation of alternative methods (ECVAM). To replace animal testing, it is important to develop microphysiological systems and ‘body-on-chip’ approaches that allow to account for organ-to-organ interactions in vitro, at a reasonable cost. Yet, most current bioreactors are expensive, designed for organ transplant (thus focused on a single organ) and poorly designed for miniaturization and scale-up. In SMD-SPH, we will develop a microphysiological systems with the following design requirement: a 3D cell culture model, with a continuous and controllable perfusion system for continuous contact with morphogens (growth factors) to obtain a functional native tissue and  monitoring crucial parameters of cell physiology, compatible with scale-up manufacturing. To the best of our knowledge, it is the first time in scientific literature that human adipose tissue-derived stem cells are used to build human white adipose tissue in a novel and scalable microphysiological system. This project meets the convergence of microfluidics and scaffold-free 3D culture models offering a reliable alternative for drug and toxicology assays, besides offer a scalable and reproductible system for future integration into a human-on-a-chip and high-troughput assays. Once an initial prototype is obtained, we will start dissemination to stakeholders and seek early adopters, cosmetic industries.
Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study

Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, was shown to be clinically active and tolerable in patients with advanced urothelial carcinoma and prespecified FGFR alterations in the primary analysis of the BLC2001 study at median 11 months of follow-up. We aimed to assess the long-term efficacy and safety of the selected regimen of erdafitinib determined in the initial part of the study.The open-label, non-comparator, phase 2, BLC2001 study was done at 126 medical centres in 14 countries across Asia, Europe, and North America. Eligible patients were aged 18 years or older with locally advanced and unresectable or metastatic urothelial carcinoma, at least one prespecified FGFR alteration, an Eastern Cooperative Oncology Group performance status of 0-2, and progressive disease after receiving at least one systemic chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy or were ineligible for cisplatin. The selected regimen determined in the initial part of the study was continuous once daily 8 mg/day oral erdafitinib in 28-day cycles, with provision for pharmacodynamically guided uptitration to 9 mg/day (8 mg/day UpT). The primary endpoint was investigator-assessed confirmed objective response rate according to Response Evaluation Criteria In Solid Tumors version 1.1. Efficacy and safety were analysed in all treated patients who received at least one dose of erdafitinib. This is the final analysis of this study. This study is registered with ClinicalTrials.gov, NCT02365597.Between May 25, 2015, and Aug 9, 2018, 2328 patients were screened, of whom 212 were enrolled and 101 were treated with the selected erdafitinib 8 mg/day UpT regimen. The data cutoff date for this analysis was Aug 9, 2019. Median efficacy follow-up was 24·0 months (IQR 22·7-26·6). The investigator-assessed objective response rate for patients treated with the selected erdafitinib regimen was 40 (40%; 95% CI 30-49) of 101 patients. The safety profile remained similar to that in the primary analysis, with no new safety signals reported with longer follow-up. Grade 3-4 treatment-emergent adverse events of any causality occurred in 72 (71%) of 101 patients. The most common grade 3-4 treatment-emergent adverse events of any cause were stomatitis (in 14 [14%] of 101 patients) and hyponatraemia (in 11 [11%]). There were no treatment-related deaths.With longer follow-up, treatment with the selected regimen of erdafitinib showed consistent activity and a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma and prespecified FGFR alterations.Janssen Research & Development.
A Fresh Look at Road Salt: Aquatic Toxicity and Water-Quality Impacts on Local, Regional, and National Scales

A new perspective on the severity of aquatic toxicity impact of road salt was gained by a focused research effort directed at winter runoff periods. Dramatic impacts were observed on local, regional, and national scales. Locally, samples from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia dubia and Pimephales promelas bioassays during road-salt runoff. Another Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous specific conductance was monitored as a chloride surrogate in 11 watersheds with urban land use from 6.0 to 100%. Elevated specific conductance was observed between November and April at all sites, with continuing effects between May and October at sites with the highest specific conductance. Specific conductance was measured as high as 30,800 μS/cm (Cl = 11,200 mg/L). Chloride concentrations exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites, respectively. Nationally, U.S. Geological Survey historical data were examined for 13 northern and 4 southern metropolitan areas. Chloride concentrations exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168 monitoring locations in northern metropolitan areas from November to April. Only 16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At southern sites, very few samples exceeded chronic water-quality criteria, and no samples exceeded acute criteria.
Der Glaube der Zeugen Jehovas und der ärztliche Heilauftrag

The treatment of Jehovah’s Witnesses presents physicians, particularly in surgery with challenges when a foreign blood transfusion is necessary but the patient dissents on religious grounds. However, in an acute situation the physician cannot withdraw from the affair by simply declining treatment or an intervention because there is a legal obligation to treat patients. If a competent patient makes use of the right to self-determination and refuses a blood transfusion, this wish must be respected otherwise the conditions for premeditated battery are fulfilled. In cases of incompetency the presumed wishes of the patient must be taken into account. If, as is often the case, the patient is in possession of a written document which orders a blood transfusion to be refused, such an authorization is fundamentally binding whereby here certain procedural steps must be adhered to.If a minor Jehovah’s Witness is in need of a blood transfusion but parental consent is denied, the physician is obliged to initiate proceedings with the Family Court and in emergency cases is justified in carrying out a blood transfusion to save the life of the child even against the explicit wishes of the parents.
Research on the Selection of Capital Flow Mode in Manufacturing Enterprises

The traditional mode of capital flow and the small capital flow which is based on virtual settlement in manufacturing enterprises are both introduced in the article.At the same time,the influence on the company itself and the departments in it of the two capital flow mode are analyzed too.Then,a model in order to choose the suitable conditions of the two modes is brought forward,and it is based on cost-benefit balance analysis.Compared With the traditional cash flow mode,small cash flow model can reduce procurement costs and increase sales revenue,but also increased the financing costs,financial risk cost and sales cost.When income is greater than the cost of items,the small cash flow mode may be chosen;on the other hand,the traditional cash flow mode is better.
The molecular basis of learning and memory: uncovering the link between neuronal activation and localized translation at the synapse.

During learning specific neuronal connections are strengthened and weakened to create long-term memory. This requires local regulation of the availability of proteins at the synapse, at a large distance from the cell body, in response to neuronal activity. It is generally recognized that such synaptic plasticity can be achieved through the regulation of translation of localized mRNAs at or near the synapses. Despite the importance of this mechanism in memory and our understanding of neurodegenerative diseases, the molecular basis by which neuronal activation regulates localised translation is still largely unknown in any system. 

I propose to address this deficiency by discovering the key regulatory pathway in activity dependent synaptic plasticity in the Drosophila third instar motorneuron synapse, a well established model for generalised synaptic function. My proposal is built on extremely promising unpublished observations showing that a highly conserved mRNA binding protein, Syncrip (Syp) regulates the localized translation of key synaptic mRNAs, such as the conserved scaffolding molecule Discs large, at the motorneuron synapse, in response to neuronal stimulation. Preliminary data from the lab suggests that Syp is post-translationally modified by Calcium/calmodulin-dependent protein kinase II (CaMKII), a well-known kinase that plays essential and conserved roles in memory. I propose to test the hypothesis that binding of Syp to its mRNA targets is regulated by phosphorylation by CamKII. I will test whether Syp is phosphorylated at CamKII consensus sites located in its mRNA binding domains, which have been modelled on the human structure. We will use mass spectrometry to identify these phosphorylation sites and characterise phosphorylation mutants of Syp generated by CRISPR. I also aim to discover the molecular mechanism by which Syncrip regulates the translation of its targets.
Ética y uso periodístico de la inteligencia artificial. Los medios públicos y las plataformas de verificación como precursores de la rendición de cuentas en España

La aplicación de la inteligencia artificial (IA) en el periodismo es una tendencia en desarrollo que afecta significativamente al modelo de producción y difusión periodístico. Como consecuencia, el uso de esta tecnología plantea diferentes retos éticos. En este contexto, la transparencia se sitúa como un principio clave para avanzar hacia un uso responsable de la IA por parte de los medios. El presente estudio analiza las webs corporativas y los blogs editoriales, principales espacios de rendición de cuentas, de nueve medios españoles vinculados a tres modelos profesionales diferentes: medios digitales, plataformas de verificación y entes públicos de radiotelevisión. Los resultados evidencian que ciertos medios públicos como RTVE están siendo precursores en la explicabilidad de su relación con la IA. Y por otra parte, el compromiso de las plataformas de verificación con la descripción de su metodología profesional favorece la transparencia sobre el uso que hacen de datos, algoritmos y automatizaciones.
Rotary multiposition valve

The disclosure is directed to a rotary multiposition valve for selectively directing the flow of a fluid through a plurality of paths. The valve comprises an inner member and a hollow housing with a row of ducts on its outer surface. The ducts are in fluid communication with the housing. An engaging section of the inner member is received in the housing. A seal divides the engaging section into a hollow inlet segment and a hollow outlet segment. A plurality of inlet apertures are disposed in the inlet segment and a plurality of outlet apertures are disposed in the outlet segment. The inlet apertures are disposed in a longitudinally and radially spaced-apart pattern that can be a helix. The outlet apertures are disposed in a corresponding pattern. As the inner member is rotated, whenever an inlet aperture overlaps one of the ducts, the corresponding outlet aperture overlaps a different duct, thus forming a fluid pathway.
A Method to Extract and Eliminate TEM Interference by Metallic Bodies in Tunnel Geological Anomaly Forecast

The transient electromagnetic (TEM) method is a geophysical exploration technique used in a wide range of applications such as mineral exploration, hydrogeology surveys, and underground geological mapping. In recent years, it has been applied in tunnel construction to forecast geological anomalies in front of the excavation face. However, the TEM response can be affected by metallic objects such as excavation carts and metallic support structures, which makes interpretation more difficult. The purpose of this study is twofold: to introduce a new method for extracting and eliminating TEM interference from metallic bodies in a tunnel excavation environment and to gain insight regarding the influence of metallic objects on the TEM response by physical modeling in the laboratory and studies conducted in the field. The concept of resistive limits is introduced; these limits can be used as eigenvalues in the inversion process, thus achieving more accurate identification of both the location and size of ball-shaped, low-resistivity anomalies (gouge materials) in surrounding rock that has high resistivity. Both the physical laboratory simulations and the field experiments provide insight on the interference effect of metal objects such as a steel arches or excavation carts on the TEM response. Field experiments inside a tunnel indicate that the maximum distance between the excavation cart tested and the tunnel face that can influence the TEM response is 30 m, while the maximum influence distance of a steel arch is 1 m in the vertical plane of the coil and 2 m in the axial direction. The proposed inversion process was shown to be capable of extracting the interference of metallic objects from TEM responses and improve the accuracy of TEM interpretation in identifying geological anomalies.