Miracle-dz/UniFAR-FTUs huggingface dataset:
Abstract LB-153: KY1055, a novel ICOS-PD-L1 bispecific antibody, efficiently enhances T cell activation and delivers a potent anti-tumour response in vivo

Antibodies blocking the PD-1/PD-L1 axis present significant breakthroughs in the treatment of hitherto untreatable cancers. However, despite the highly encouraging progress that has been made, multiple tumour types demonstrate limited response to these therapies. The emerging picture is that combination with other therapies is required to improve response rates and/or the durability of response. Additional benefit could be achieved by combining an anti-PD-L1 approach with another modulator of T cell activation. ICOS is a co-stimulatory molecule expressed on activated T cells such as TEff and TReg cells present in the tumour microenvironment (TME). ICOS agonism has been demonstrated to improve TEff cell survival and IFNγ release, resulting in the activation of T cell-dependent eradication of the tumour. In addition, the high expression of ICOS observed on TReg cells in the TME allows these highly immunosuppressive cells to be selectively depleted when using the appropriate antibody format. With the aim of targeting both ICOS and PD-L1, we have developed a bispecific mAb² (KY1055) as a human IgG1 format that consists of fully human Fab arms targeting ICOS and a modified Fc (Fcab) containing binding sites to PD-L1. We demonstrate potent (single digit nM) binding to ICOS via the Fab and to PD-L1 via the Fcab. Furthermore, in vitro studies reveal that KY1055 can bridge together ICOS- and PD-L1-expressing cells and can activate ICOS signalling through this cross-presentation. Functionality of the Fcab was validated by demonstrating that it blocks the PD-1-PD-L1 inhibitory pathway, resulting in the up-regulation of IFNγ in monocyte:T cell co-culture assays. We also demonstrate the ability of KY1055 to deplete ICOShigh cells in vitro by ADCC. In vivo, we confirm the anti-tumour efficacy of KY1055 in several syngeneic models that are poorly responsive to the respective monotherapies and further demonstrate improved anti-tumour efficacy when combined with anti-CTLA4 and anti-PD-1 in vivo. Finally, we demonstrate that KY1055 depletes TRegs and improves the TEff : TReg ratio in vivo in a CT26 model of tumour growth. Altogether, these data warrant further development of KY1055 for the treatment of solid tumours. Citation Format: Richard C. Sainson, Nahida Parveen, Gwenoline Borhis, Miha Kosmac, Tracey OKell, Emma Taggart, Joana Carvalho, Matthew McCourt, Hanif Ali, Hannah Craig, Aksana Labokha. KY1055, a novel ICOS-PD-L1 bispecific antibody, efficiently enhances T cell activation and delivers a potent anti-tumour response in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-153.
Lectin binding pattern of selected human cell lines and its impact on improved drug delivery

Eukaryotische Zellen besitzen an der Ausenseite ihrer Zellmembran einen Kohlenhydratsaum, die sogenannte Glykocalyx, die je nach Zelltyp aus unterschiedlichen Polysacchariden besteht. Neben Proteoglykanen sind diese in der Zellmembran uber kovalente Bindung an Membranproteine oder Membranlipide verankert und konnen von biorekognitiven Proteinen wie Lektinen erkannt werden. Aufgrund dieser Fahigkeiten eignen sich Lektine zur Charakterisierung von Glykosylierungsmustern, die sich im Laufe der Entwicklung und Differenzierung, besonders aber auch im Rahmen einer malignen Transformation der Zellen verandern konnen. In der vorliegenden Dissertation wurden daher verschiedene Lektine pflanzlichen Ursprungs mit unterschiedlichen Zuckerspezifitaten ausgewahlt und deren Interaktion mit folgenden Zelllinien untersucht: humane 5637 Zellen fur Studien am Blasenkarzinom, humane C-28/I2, T/C-28a2 und primare humane Chondrozyten fur Knorpeluntersuchungen, porcine PBMEC/C1-2 und humane ECV304 Zellen fur die Charakterisierung der Blut-Hirn Schranke und humane THP-1 Zellen als Modell fur Monozyten, die die Fahigkeit besitzen zu Makrophagen zu differenzieren. Da einige dieser Zelllinien erst im Zuge der Dissertation in der Arbeitsgruppe etabliert wurden, lag ein Hauptaugenmerk auf einer detaillierten Charakterisierung dieser Zelllinien, um in Zukunft zuverlassige Ergebnisse zu erhalten. Nach Evaluierung der bioadhasiven Eigenschaften der eingesetzten Lektine sowie der Charakterisierung der Bindungsspezifitat sollte uberpruft werden, ob und in welchem Ausmas Lektine in die Zellen aufgenommen werden. Dieser Aspekt ist bei einem Einsatz von Lektinen als „targeter“ fur eine gezielte Pharmakotherapie von groser Bedeutung. In weiterer Folge wurden daher auch Weizenkeimagglutinin (WGA)-funktionalisierte Nanopartikel hergestellt und deren Aufnahme in THP-1 Zellen untersucht, wobei ahnlich wie fur WGA alleine hohe Einbauraten erzielt werden konnten. Zusammenfassend lasst sich festhalten, dass die vorliegenden Ergebnisse eine primare Bewertung des Glykosylierungsmusters der untersuchten Zelllinien erlauben und die prinzipielle Eignung eines Lektin-vermittelten Targetingkonzeptes aufzeigen, sodass diese Arbeit eine Grundlage fur weiterfuhrende in vivo-Studien darstellt.
Clarity Trumps Content: An Experiment on Information Acquisition in Beauty Contests

We provide experimental evidence that under strong beauty contest incentives, players ignore signals from an information source with high content if the source has low clarity. Instead, they acquire equally costly signals from a source with higher clarity despite its lower content. Content measures how precisely an information source identifi es an economic situation, whereas clarity measures how precisely the source content is commonly interpreted. Low clarity impairs players' ability to coordinate. When signals are provided exogenously, our experimental results are less severe than theoretical predictions, but consistent with level-2 reasoning in a cognitive behavioral model. When players acquire signals endogenously, ignoring a high-content source is more severe than theoretical predictions. Our results imply that when beauty contest incentives are strong (e.g., short-horizon trading), investors can completely ignore a firm's disclosure, despite its high content, if the disclosure is not sufficiently clear.
Nonparametric Econometrics: Theory and Practice

Until recently, students and researchers in nonparametric and semiparametric statistics and econometrics have had to turn to the latest journal articles to keep pace with these emerging methods of economic analysis. Nonparametric Econometrics fills a major gap by gathering together the most up-to-date theory and techniques and presenting them in a remarkably straightforward and accessible format. The empirical tests, data, and exercises included in this textbook help make it the ideal introduction for graduate students and an indispensable resource for researchers. Nonparametric and semiparametric methods have attracted a great deal of attention from statisticians in recent decades. While the majority of existing books on the subject operate from the presumption that the underlying data is strictly continuous in nature, more often than not social scientists deal with categorical data--nominal and ordinal--in applied settings. The conventional nonparametric approach to dealing with the presence of discrete variables is acknowledged to be unsatisfactory. This book is tailored to the needs of applied econometricians and social scientists. Qi Li and Jeffrey Racine emphasize nonparametric techniques suited to the rich array of data types--continuous, nominal, and ordinal--within one coherent framework. They also emphasize the properties of nonparametric estimators in the presence of potentially irrelevant variables. Nonparametric Econometrics covers all the material necessary to understand and apply nonparametric methods for real-world problems.
O Ambiente Institucional na Viticultura do município de Jales-SP

: O processo produtivo da uva de mesa na regiao noroeste de Sao Paulo iniciou-se na decada de 1960 e atualmente apresenta-se como atividade de grande importância, por ser uma alternativa de ocupacao e geracao de renda para o pequeno produtor rural. O Municipio de Jales e considerado o maior produtor de uvas de mesa da regiao. Este trabalho objetiva a descricao do ambiente institucional presente na producao de uva de mesa de Jales-SP, tendo como base os estudos da Nova Economia Institucional. Para cumprir os objetivos propostos, foram utilizados dados primarios e secundarios, bem como entrevista semiestruturada com os principais agentes institucionais presentes na regiao e com os produtores da viticultura local. Verificou-se a existencia de um ambiente institucional fragilizado por nao estimular a continuidade da cultura, o que poderia ser realizado atraves de politicas publicas direcionadas especificamente a viticultura, como presenca de uma linha de credito que atendesse a demanda dos produtores. Outras atitudes poderiam motivar a continuidade e maiores investimentos na cultura, como por exemplo, um agente institucional que coordenasse as atividades, promovendo o produto, gerando confianca nos demais agentes institucionais, atraves de maior articulacao e envolvimento entre esses.
Prevention of Diabetes and 4P Medicine

In the last decades (more visibly in the last 20 years), there has been a progressive increase in the prevalence and incidence of Diabetes Mellitus (DM) on a global scale, irrespective of the economic development of various regions (high, middle or low income countries), especially in developing countries. “It may yet be, along with obesity, the greatest chronic disease epidemic in the history of human existence” [1]. The International Diabetic Federation (IDF) has reported for 2015, globally, a number of 415 million adults (aged between 20 and 79), with DM (8,8%), estimating an increase to 642 million by 2040 [2]. This increase is mainly due to the surge in the number of people with Type 2 DM but also to the rise in incidence of Type 1 DM and gestational DM, a form of diabetes which is still under-investigated and underdiagnosed. The prevalence of Type 2 DM increases with age, being more frequent in men in comparison with women; overweight and obesity as well as unhealthy lifestyle are important factors of this rise [1,2]. DM is associated with a high risk of morbidity and premature mortality, especially due to cardiovascular reasons, complex health care teams being needed to train the patient suffering with diabetes the way they should permanently adapt medication to their type of diet, the level of physical exercises, the various events which can produce a diabetes’ temporary imbalance. It is well known that the patients who suffer from DM need more outpatient consultations, show a greater number of days of hospitalization, and the occurrence of the devastating chronic complications (micro, macrovascular) or comorbidity severely affects the health state of these relatively young patients, their work ability decreases, being often in need of a companion. The mortality of patients suffering from DM exhibits an increasing tendency and exceeded, in 2015, the figure of 5 million, compared to 1,5 million in 2012 and 1,1 million in 2005 [2,3].
How Important Is the Problem of Malnutrition in Chronic Dialysis Patients?

Malnutrition is now being recognized as an important factor that has an adverse impact on the morbidity and mortality of hemodialysis patients. This was suggested a decade ago with the publication of the National Cooperative Dialysis Study (NCDS) (1). In the NCDS, low protein catabolic rates (PCRs) reflecting inadequate protein intake were associated with increased hospitalization and treatment failure. An analysis by Acchiardo et al. (2) demonstrated that individuals with low PCR experienced more intercurrent illness, as well as mortality, compared to patients with higher PCR. There are many reasons for malnutrition in the hemodialysis population. Among them are the poor appetite seen in chronically ill individuals, dietary restrictions that limit the choice and palatability of food, frequent hospitalizations and the need for surgical procedures, depression, endocrine abnormalities that may interfere with the incorporation of nutrients, and inadequate dialysis and dialysis-induced catabolism. It is becoming clear that issues related to the hemodialysis treatment itself may be of great importance in determining the nutritional status of patients. Understanding this relationship between nutrition and dialysis technique is particularly important, since changes in the dialysis prescription or in the type of membrane employed may ultimately benefit the patient, as discussed below. A retrospective analysis of laboratory data obtained from a large group of patients receiving maintenance hemodialysis has demonstrated a striking relationship between hypoalbuminemia (a reflection of poor protein intake) and annual mortality rates (3). It is particularly disturbing that patients with albumin levels between 3.5 and 4.0 g/dl had a risk of mortality that was twofold greater than patients with albumin levels greater than 4.0 g/dl. Prior to the publication of this data, albumin levels in the range of 3.5-4.0 g/dl certainly would not have caused alarm among practitioners, yet even this modest reduction appears to be a harbinger of increased mortality. In the same study, a further reduction in serum albumin levels produced even greater increases in mortality (fivefold higher for patients with
Asymptotic SINR analysis of single-user MC-CDMA in Rayleigh fading

This paper considers multi-carrier (MC) CDMA communication systems. A broadband ad-hoc network is considered where single users employ multiple codes. The receiver structure is linear and minimizes the mean square error of the data estimate. Using asymptotic analysis, the average output signal to interference plus noise ratio (SINR) is derived as a function of the channel loading, the noise power, and the fading properties of the channel. An expression for the BER for BPSK/QPSK symbols is given and supported by simulation results. A less complex approximate method for computing the SINR is also derived. Simulations show that these asymptotic SINR are applicable to realistic finite systems.
Research on Interactive Acquisition and Use of Knowledge.

Abstract : SRI International is engaged in a long-term research effort under DARPA sponsorship to develop techniques for facilitating the acquisition of knowledge of computers. The ultimate goal is to build KLAUS(Knowledge-Learning and -Using System), a computer program that could acquire a model of a domain of interest by being instructed in English. The model could then be used for domain-related tasks. Systems based on the KLAUS concept would be useful for a variety of applications, including sophisticated interfaces to computer software, advanced database systems, and intelligent computer assistants. This report covers work done on the KLAUS project during the period July 1981 to January 1982. Section 2 describes DIALOGIC, the natural-language processing system used in MICROKLAUS, which is our current preliminary implementation of the KLAUS concept. The dialogic system translates English sentences into representation of their literal meaning in the context of an utterance. Section 3 describes a new scheme for syntax-directed translation of natural language into logical form. That scheme, comprising the basis of an English translation system called PATR, was used to specify a semantically interesting fragment of English that included such constructs as tense, aspect, modals, and various lexically controlled verb complement structures.
La malattia glaucomatosa dal punto di vista del paziente

Scopo: valutare l’impatto psicologico dell’annuncio della diagnosi di glaucoma e annotare il punto di vista dei pazienti riguardo le informazioni, il trattamento e le cure ricevute. Materiali e metodi: 56 pazienti trattati per glaucoma primario ad angolo aperto o per ipertensione oculare hanno completato un questionario di 28 domande in seguito ad una visita regolare dal proprio oculista. Il questionario e stato progettato per analizzare le reazioni dei pazienti in seguito alla diagnosi, per registrare le informazioni ricevute, il trattamento prescritto, e per valutare la compliance alla terapia e alle visite. I pazienti sono stati studiati in base al sesso e all’eta. I risultati sono presentati come frequenze e percentuali. Le differenze sono state valutate per mezzo dei test Chi-quadro e Fisher. Risultati: oltre il 70% dei pazienti ha avuto un approccio emotivo negativo alla diagnosi: il 35.7% ha avuto paura di diventare cieco, il 26.7% ha provato ansia (i pazienti piu giovani di piu in confronto a quelli piu anziani, p=0.048). Quasi la meta dei pazienti ha dichiarato di aver modificato il proprio atteggiamento riguardo la cura dei propri occhi (soprattutto i pazienti piu giovani e le donne). Il 78% dei pazienti e risultato soddisfatto delle informazioni ricevute e delle cure prestate, nonostante la loro conoscenza della malattia fosse incompleta, solo il 21.4% sapeva infatti che l’ereditarieta e la pressione intraoculare elevata erano le cause del glaucoma. Circa l’84% ha richiesto maggiori chiarimenti riguardo la causa, l’evoluzione e la prevenzione della patologia. I pazienti piu giovani (95%) e le donne (90%) hanno chiesto di piu. I 4/5 dei pazienti usavano una terapia topica, e 2/3 (soprattutto giovani e donne) hanno riportato degli effetti avversi soprattutto prurito, bruciore e lacrimazione, nonostante cio nessun paziente ha interrotto la terapia. L’ostacolo principale alla compliance e stato la dipendenza del paziente da qualcuno per instillare il collirio. Circa la meta dei pazienti si e rivelata d’accordo rispetto alla frequenza delle visite di follow-up e del campo visivo. Conclusioni: l’annuncio della diagnosi di glaucoma e un momento fondamentale nel rapporto medico-paziente ed influenza negativamente la qualita di vita del paziente, e necessaria percio un’informazione personalizzata del paziente. Nonostante l’eta e il sesso influenzino le reazioni alla diagnosi e la soddisfazione riguardo le informazioni e le cure fornite, la maggior parte dei pazienti si sono detti soddisfatti degli oculisti curanti. I trattamenti prescritti sono generalmente risultati ben accettati e la compliance riferita e risultata elevata.
EXTRACTION OF BUILT-UP AREAS USING CONVOLUTIONAL NEURAL NETWORKS AND TRANSFER LEARNING FROM SENTINEL-2 SATELLITE IMAGES

Abstract. With rapid globalization, the extent of built-up areas is continuously increasing. Extraction of features for classifying built-up areas that are more robust and abstract is a leading research topic from past many years. Although, various studies have been carried out where spatial information along with spectral features has been utilized to enhance the accuracy of classification. Still, these feature extraction techniques require a large number of user-specific parameters and generally application specific. On the other hand, recently introduced Deep Learning (DL) techniques requires less number of parameters to represent more abstract aspects of the data without any manual effort. Since, it is difficult to acquire high-resolution datasets for applications that require large scale monitoring of areas. Therefore, in this study Sentinel-2 image has been used for built-up areas extraction. In this work, pre-trained Convolutional Neural Networks (ConvNets) i.e. Inception v3 and VGGNet are employed for transfer learning. Since these networks are trained on generic images of ImageNet dataset which are having very different characteristics from satellite images. Therefore, weights of networks are fine-tuned using data derived from Sentinel-2 images. To compare the accuracies with existing shallow networks, two state of art classifiers i.e. Gaussian Support Vector Machine (SVM) and Back-Propagation Neural Network (BP-NN) are also implemented. Both SVM and BP-NN gives 84.31 % and 82.86 % overall accuracies respectively. Inception-v3 and VGGNet gives 89.43 % of overall accuracy using fine-tuned VGGNet and 92.10 % when using Inception-v3. The results indicate high accuracy of proposed fine-tuned ConvNets on a 4-channel Sentinel-2 dataset for built-up area extraction.
Identification of Wiener-MLP with feedback NOE-model with extended Kalman filter

The classical input-output Wiener-representation consists of linear dynamics (Laguerre filters) and static nonlinear static polynomial mapping. In Wiener-MLP the static nonlinear mapping is realized with MLP. By feeding back some of the outputs of Wiener-MLP, a model capable of modeling autonomous systems, like batch processes, can be realized. The dynamics contains MLP and Laguerre system in the feedback loop. The model can be presented in state-space form. The MLP can be interpreted as the measurement equation of the system. An extended Kalman filter is used in recursive NOE-type estimation of the MLP parameters in order to identify a model suitable for simulation. Wiener-MLP with feedback models are identified for two bioprocesses.
A Novel Framework for Gene Selection

Microarray data are highly redundant and noisy, and most genes are believed to be uninformative with respect to studied classes, as only a fraction of genes may present distinct profiles for different classes of samples. This paper proposed a novel hybrid framework (NHF) for the classification of high dimensional microarray data, which combined information gain(IG), F-score, genetic algorithm(GA), particle swarm optimization(PSO) and support vector machines(SVM). In order to identify a subset of informative genes embedded out of a large dataset which is contaminated with high dimensional noise, the proposed method is divided into three stages. In the first stage, IG is used to construct a ranking list of features, and only 10% features of the ranking list are provided for the second stage. In the second stage, PSO performs the feature selection task combining SVM. F-score is considered as a part of the objective function of PSO. The feature subsets are filtered according to the ranking list from the first stage, and then the results of it are supplied to the initialization of GA. Both the SVM parameter optimization and the feature selection are dynamically executed by PSO. In the third stage, GA initializes the individual of population from the results of the second stage, and an optimal result of feature selection is gained using GA integrating SVM. Both the SVM parameter optimization and the feature selection are dynamically performed by GA. The performance of the proposed method was compared with that of the PSO based, GA based, Ant colony optimization (ACO) based and simulated annealing (SA) based methods on five benchmark data sets, leukemia, colon, breast cancer, lung carcinoma and brain cancer. The numerical results and statistical analysis show that the proposed approach is capable of selecting a subset of predictive genes from a large noisy data set, and can capture the correlated structure in the data. In addition, NHF performs significantly better than the other methods in terms of prediction accuracy with smaller subset of features.
A primer for understanding and applying data mining

Data mining is such a hot topic that it has become an obscured buzzword. Data mining can be a powerful tool for extracting useful information from tons of data. But it can just as easily extract erroneous and useless information if it's not used correctly. Key to avoiding the pitfalls is a basic understanding of what data mining is and what things to consider in planning a data mining project. The steps in a data mining project include: integrating and cleaning or modifying the data sources, mining the data, examining and pruning the mining results, and reporting the final results.