SIRIS-Lab/unlabelled-sti-corpus huggingface dataset:
Protac linker design: towards functionality

Proteolysis Targeting Chimeras (PROTACs), small molecules capable of inducing degradation of a target protein, represent a novel strategy to design advanced chemical probes and therapeutic agents with the potential to target so far “undruggable” proteins. PROTACs are heterobifunctional molecules consisting of binding ligands to an E3 ubiquitin ligase and a protein of interest, covalently connected by a linker. Formation of a ternary complex of target protein, PROTAC and E3 ligase allows ubiquitination of the target protein, leading to its subsequent degradation by the proteasome. Due to the complexity of this ternary system, rational PROTAC design is highly challenging and novel PROTACs are to date commonly derived from trial-and-error approaches, typically using simple linkers to connect the two binding ligands. The potential to significantly stabilize and in doing so bias productive ternary complex formation, through design of functional linkers has not been exploited so far. My goal for this project is to identify and explore novel functional linker motifs which will enhance interactions within the ternary complex, such as PROTAC-ligase, PROTAC-target as well as cross-interactions between the E3 ligase and the target protein. The effects of halogen bonding, metal coordination and restricted conformational flexibility of the PROTAC linker on ternary complex formation and PROTAC degradation activity and efficiency will be systematically studied, benchmarked against related PROTAC degraders with non-functionalized linkers and taken as the basis to derive valuable structure-activity relationships. My long-term vision is to capitalize on this Fellowship to enhance my career by developing a rational-design strategy for novel PROTAC degraders capitalizing on functionalized linkers to efficiently degrade proteins so far considered to be “undruggable”.
Fish otolith geochemistry, environmental conditions and human occupation at Lake Mungo, Australia

Abstract Fish otoliths from the Willandra Lakes Region World Heritage Area (south-western New South Wales, Australia) have been analysed for oxygen isotopes and trace elements using in situ techniques, and dated by radiocarbon. The study focused on the lunettes of Lake Mungo, an overflow lake that only filled during flooding events and emptied by evaporation, and Lake Mulurulu, which was part of the running Willandra Creek system. Samples were collected from two different contexts: from hearths directly associated with human activity, and isolated surface finds. AMS radiocarbon dating constrains the human activity documented by five different hearths to a time span of less than 240 years around 19,350 cal. BP. These hearths were constructed in aeolian sediments with alternating clay and sand layers, indicative of fluctuating lake levels and occasional drying out. The geochemistry of the otoliths confirms this scenario, with shifts in Sr/Ca and Ba/Ca marking the entry of the fish into Lake Mungo several years before their death, and a subsequent increase in the δ 18 O by ∼4‰ indicating increasing evaporation of the lake. During sustained lake-full conditions there are considerably fewer traces of human presence. It seems that the evaporating Lake Mungo attracted people to harvest fish that might have become sluggish through oxygen starvation in an increasingly saline water body ( easy prey hypothesis). In contrast, surface finds have a much wider range in radiocarbon age as a result of reworking, and do not necessarily indicate evaporative conditions, as shown by comparison with otoliths from upstream Lake Mulurulu.
Digitally Assisted Analog Interference Cancellation for In-Band Full-Duplex Radios

In this letter, a digitally assisted analog interference cancellation architecture is proposed for the prevailing full-duplex radios, which simultaneously transmit and receive signals on the same carrier frequency. An auxiliary transmit chain is deployed to generate a canceling signal and subtract from the self-interference (SI) signal at the receiver front end to prevent saturating the analog-to-digital converter. To ensure the canceling signal a close approximation of the SI signal, an observation chain is used to extract the transmitter response. Correspondingly, a two-step modeling process is inserted to the auxiliary transmit chain to recover both the nonlinear behavior and the multi-path channel between the transmit and receive chains. Experimental results have validated the superior performance of this architecture, particularly for transmitters of high output power and strong nonlinear distortions.
Developing instrument to increase students' geometry ability based on Van Hiele level integrated with Riau Malay culture

The purpose of this research is to develop Geometry teaching materials and geometry instruments that can be used to improve the ability of Geometry based on Van Hiele's cognitive level integrated with Malay Culture. The research design used in this research was Research and Development (R&amp;D) which consists of several stages, namely: potential and problems, material collection, product design, product validity, product trials, product revisions, and mass products. The subjects of this study were students of mathematics education department in the first semester consisting of 65 students. The Validity of Teaching Materials inform students work sheet was analyzed using the validation sheets of teaching materials proposed by Akbar (2013) and Practical Analysis was analyzed using the formula proposed by Riduan (2016). The test instrument was analyzed using Aiken's validity and interrater reliability. The questionnaire instrument was analyzed using Aiken's validity and interrater reliability. Data analysis shows that teaching materials are in the form of student worksheets in the valid and practical categories. The test instrument was developed in valid and reliable categories. The developed questionnaire instrument in the form of essays in a valid and reliable category. Teaching materials and instruments in the form of questionnaires and essays according to experts can be used to obtain relevant data and improve the ability of geometry based on the level of Van Hiele integrated with Malay Culture.
Attosecond imaging and control of chemical dynamics

Femtosecond laser pulses can be exploited to trace the ultrafast motion of electrons (“attosecond physics”) and study the properties of molecules, and the changes they undergo, on the atomic scale (“femtochemistry”). Suitable tailoring of the laser fields even allows for controlling the electron and nuclear dynamics within molecules and thereby steer chemical reactions towards a desired outcome (“coherent control”). Despite a wide range of perspective applications in fundamental science and industry, our capabilities to exert control on chemical reactions, and our understanding thereof, have been very limited. In the proposed work, I will develop and employ a novel experimental technique, which will allow (a) controlling light-induced chemical reactions in a wide range of molecular species efficiently, and (b) imaging the electron and nuclear dynamics underlying such reactions on their natural timescales. My work will go significantly beyond the state-of-the-art and thus contribute to the development of coherent control and our microscopic understanding of photochemical reactions. The advancements become possible by combining the latest laser technology with the expertise of all participants. The proposed MSCA will complement my scientific skills, both experimental and theoretical, and will provide me with required transferable skills to reach my long-term goal of establishing my own research group in Europe. The new scientific development will contribute to consolidating the European Leadership in the field of Attosecond Physics.
Decay heat studies for nuclear energy

The energy associated with the decay of fission products plays an important role in the estimation of the amount of heat released by nuclear fuel in reactors. In this article we present results of the study of the beta decay of some refractory isotopes that were considered important contributors to the decay heat in reactors. The measurements were performed at the IGISOL facility of the University of Jyvaskyla, Finland. In these studies we have combined for the first time a Penning trap (JYFLTRAP), which was used as a high resolution isobaric separator, with a total absorption spectrometer. The results of the measurements as well as their consequences for decay heat summation calculations are discussed.
Stereodynamical Origin of Anti-Arrhenius Kinetics: Negative Activation Energy and Roaming for a Four-Atom Reaction

The OH + HBr → H2O + Br reaction, prototypical of halogen-atom liberating processes relevant to mechanisms for atmospheric ozone destruction, attracted frequent attention of experimental chemical kinetics: the nature of the unusual reactivity drop from low to high temperatures eluded a variety of theoretical efforts, ranking this one among the most studied four-atom reactions. Here, inspired by oriented molecular-beams experiments, we develop a first-principles stereodynamical approach. Thermalized sets of trajectories, evolving on a multidimensional potential energy surface quantum mechanically generated on-the-fly, provide a map of most visited regions at each temperature. Visualizations of rearrangements of bonds along trajectories and of the role of specific angles of reactants' mutual approach elucidate the mechanistic change from the low kinetic energy regime (where incident reactants reorient to find the propitious alignment leading to reaction) to high temperature (where speed hinders adjustment of directionality and roaming delays reactivity).
High cycle fatigue prediction methodology for fibre reinforced laminates for aircraft structures in cror environment – development and validation

The aim is to develop high cycle fatigue (HCF) testing capabilities for composite materials to study the long-term fatigue life of composite laminates used in new structural architectures subjected to high sound pressure loading in CROR environment.

The achievement of the overall project aim will be tackled through the accomplishment of two technical objectives: developing a sound source and amplification system representative of the high sound pressure generated by the CROR; developing and validating an enhanced accelerated fatigue prediction methodology framework to HCF life prediction of CFRP laminates used in the new aero-structures configurations in CROR environment.  

Concepts for the sound source and amplification system will be designed according to the specifications. The best concept will be demonstrated and validated and successively the system will be manufactured and delivered to Fraunhofer IBP. The development of the methodology framework for HCF prediction of CFRP materials will be achieved through extensive experimental testing, physical analysis and numerical FE modelling activities. Following on from existing approaches, the final outcome of the project will be an expanded methodology framework for HCF prediction of CFRP laminates able to take into account the influence of environmental conditions as well as the presence of frequency dependent phenomena (e.g self heating). The framework will consist of fatigue models based on fatigue master curves and shift as well as FE predictive models that can be used as virtual assessment tools for HCF performance of CFRP materials.

The immediate impact of the project will be providing the IADP’s Partners and the aerospace community with advanced testing capabilities to facilitate the design process and the structural integrity assessment of the new aero-structure configurations as result of the CROR integration in order to meet safety and certification requirements.
Characterizing the occipital oscillatory activity in blindness

The massive reorganization of the occipital regions as a consequence of lack of vision represents one of the most
remarkable examples of the plastic potentialities of the human brain. Despite the large amount of neuroimaging evidence
proving the involvement of occipital areas of blind individuals in non‐visual input processing, the functional role of this
sensory reorganized region is still matter of intense debate. In COcOAB, we will use an underexploited neuroimaging
technique in this field, magnetoencephalography (MEG), in order to study the oscillatory profile of ensembles of occipital
neurons and their brain‐wide functional interaction patterns in blind individuals. This will allow us to gather unprecedented
information about the functional relevance of non‐visual activity in the occipital cortex of blind individuals. Moreover,
COcOAB will assess the impact of age onset and duration of visual deprivation on the occipital oscillatory activity, thus
providing insights into the relationship between blindness and sensitive periods of maturation in the visual system. The
groundbreaking potentials of COcOAB reside in the application of the MEG technique to the study of two experimental
domains — sensory illusions and stimulation at threshold — that has been so far neglected in the field of sensory
deprivation. COcOAB represents a unique testing ground to address how specific regions support perception in a
mechanistic fashion in visually deprived individuals, thus challenging the current knowledge on the functionality of these
reorganized regions via a highly innovative approach.
Indirect dark matter signatures in the cosmic dark ages. II. Ionization, heating, and photon production from arbitrary energy injections

Any injection of electromagnetically interacting particles during the cosmic dark ages will lead to increased ionization, heating, production of Lyman-alpha photons and distortions to the energy spectrum of the cosmic microwave background, with potentially observable consequences. In this note we describe numerical results for the low-energy electrons and photons produced by the cooling of particles injected at energies from keV to multi-TeV scales, at arbitrary injection redshifts (but focusing on the post-recombination epoch). We use these data, combined with existing calculations modeling the cooling of these low-energy particles, to estimate the resulting contributions to ionization, excitation and heating of the gas, and production of low-energy photons below the threshold for excitation and ionization. We compute corrected deposition-efficiency curves for annihilating dark matter, and demonstrate how to compute equivalent curves for arbitrary energy-injection histories. These calculations provide the necessary inputs for the limits on dark matter annihilation presented in the accompanying Paper I, but also have potential applications in the context of dark matter decay or de-excitation, decay of other metastable species, or similar energy injections from new physics. We make our full results publicly available at http://nebel.rc.fas.harvard.edu/epsilon, to facilitate further independent studies. In particular, we provide the full low-energy electron and photon spectra, to allow matching onto more detailed codes that describe the cooling of such particles at low energies.
Perfusion and metabolism imaging studies in Parkinson's disease.

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are important tools in the evaluation of brain blood flow and glucose metabolism in Parkinson's disease (PD). However, conflicting results are reported in the literature depending on the type of imaging data analysis employed. The present review gives a comprehensive summary of the perfusion and metabolism literature in the field of PD research, including quantitative PET studies, normalized PET and SPECT studies, autoradiography studies in animal models of PD, and simulation studies of PD data. It is concluded that PD most likely is characterized by widespread cortical hypometabolism, probably even at early disease stages. Widespread subcortical hypermetabolism is probably not a feature of PD, although certain small basal ganglia structures, such as the external pallidum, may display true hypermetabolism in the absolute sense. This observation is also in agreement with the animal literature.
Challenging the oxidation-state limitations of the periodic table via high-pressure fluorine chemistry

The HiPeR-F project aims to establish a new frontier research direction – high-pressure fluorine chemistry, by method development and a merger of two highly specialised and experimentally demanding fields, namely high-pressure experiments in diamond anvil cell and inorganic fluorine chemistry. Fluorine under high pressure represents a breakthrough testing environment for challenging the oxidation-state limitations of the elements in the periodic table. Tantalizing theoretical indications have been provided recently for the existence of compounds with elements displaying unusual and exotic formal oxidation states, and even the possibility of the inner electronic shell involvement in chemical bonding. However, extreme conditions of very high pressure (in GPa range) and extreme chemical reactivity (fluorine) are required and this is currently limited to in silico investigations. Experiment lags substantially behind the theory. The experimental verification of exciting computational predictions is of paramount importance and will be pursued in HiPeR-F. Targeted compounds with elements in exotic oxidation states are at the edge of existence and are eminently difficult to synthesise, but are also of significant interest to the scientific community at large. Novel compounds obtained in high-pressure experiments could exhibit unusual electronic structures and thus exotic physical properties. High-pressure fluorochemistry thus represents a genuine new direction in modern chemistry with exciting possibilities and would enable a frontier research that would significantly advance our understanding of many facets of chemistry.
A XML Information Integration Model Based on Ontology

In order to meet the requirement better of heterogeneous information integration, this paper proposes a XML information integration model based on ontology technology. This model comes to share and reuse of structured knowledge, explicitness of domain knowledge. According to mapping method from ontology to XML schema, the model also comes to document query based on global semantic, solves the semantic heterogeneity of XML information integration. This paper gives a mapping algorithm to implement the validated verify of XML semantic information for automatic indexing information. Finally, this paper explained simply the query algorithm so that the users can conveniently the query of heterogeneous XML information.
Where to park? minimizing the expected time to find a parking space

Quickly finding a free parking spot that is close to a desired target location can be a difficult task. This holds for human drivers and autonomous cars alike. In this paper, we investigate the problem of predicting the occupancy of parking spaces and exploiting this information during route planning. We propose an MDP-based planner that considers route information as well as the occupancy probabilities of parking spaces to compute the path that minimizes the expected total time for finding an unoccupied parking space and for walking from the parking location to the target destination. We evaluated our system on real world data gathered over several days in a real parking lot. We furthermore compare our approach to three parking strategies and show that our method outperforms the alternative behaviors.
The Role of Logistics in E-commerce Transactions: An Exploratory Study of Customer Feedback and Risk

AbstractLogistics plays an important role in e-commerce; while most part of the transactions happen electronically, physical products need to be shipped to customers using conventional transport means. We report in this paper an exploratory study to understand how customers view logistics performance in deciding performance of sellers in e-commerce. Since it has been observed that risk plays a stronger role in online transactions compared to offline transactions, we study how the importance of logistics performance is influenced by risk characteristics of products sold through e-commerce websites. Our data for analysis have been derived from customer feedback available in eBay. Based on Chi square tests and the Marascuilo procedure, we find that the importance of logistics services increases as risk characteristics of products decreases from high to low.KeywordsLogisticsE-commerceProduct risk
Magnification of asthma by human memory group 2 innate lymphoid cells

Allergen-sensitized individuals may develop chronic airway inflammation, typically found in asthmatic patients. This process is thought to be mediated by the generation of antigen-specific memory Th2 cells, which respond stronger during subsequent encounters with the same allergen. The characterization of memory T cells has led to the development of vaccination therapies to produce desensitization towards specific antigens. However, these treatments are not always effective as some asthmatic patients respond to a wide range of allergens in a non-specific manner. The causes for this non-specific allergic response are currently unknown.
 
This action postulates that Group 2 innate lymphoid cells, critical players in lung allergic inflammation, fill this gap of knowledge. The researcher showed that allergen-experienced mouse lung ILC2s acquire memory functions: remember previous allergen exposures and react stronger upon subsequent exposure to an unrelated allergen. The goal of this proposal is to demonstrate that human memory ILC2s are involved in asthma exacerbation and that IL-25 might be a target to ameliorate memory ILC2-mediated lung inflammation in these patients. The supervisor is an expert in human ILCs. Humanized mice will be used to define the phenotype and function of human memory ILC2 and the results will be further validated on peripheral blood and sputum samples from asthmatic patients.
 
Asthma is considered by the World Health Organization the most common chronic lung disease worldwide with a substantial social and economic burden due to its high rate of under-diagnosis and under-treatment. Specific focus will be to raise awareness of clinicians and pharmaceutical companies about the potential of memory ILC2 as a target to improve diagnosis and treatment. This project will translate the researcher’s knowledge in to a human setting and provide a wealth of data to obtain further funding and become a research group leader in Europe.
ENCAPSULATED ACTIVE INGREDIENTS, METHODS OF PREPARATION AND THEIR USE

The present invention relates to particles comprising an active ingredient. The active ingredient is encapsulated by coacervation, and further encapsulated by a glassy matrix. The glassy matrix comprises 3-50wt% of a hydrophobically modified starch, and 50-97wt% of a starch hydrolysate. The particles are useful for encapsulating active ingredients intended for oral ingestion and may be added to food products.