Miracle-dz/UniFAR-FTUs huggingface dataset:
DYNAMICS OF PROTEIN STRUCTURES AND ITS IMPACT ON LOCAL STRUCTURAL BEHAVIORS.

Protein structures are highly dynamic in nature contrary to their depiction in crystal structures. A major component of structural dynamics is the inherent protein flexibility. The prime objective of this thesis is to understand the role of the inherent dynamics in protein structures and its propagation. Protein flexibility is analyzed at various levels of structural complexity, from primary to quaternary levels of organization. Each of the first five chapters’ deal with a different level of local structural organization with first chapter dealing with classical secondary structures while the second one analysis the same using a structural alphabet - Protein Blocks. The third chapter focuses on the impact of special physiological events like post-translational modifications and disorder to order transitions on protein flexibility. These three chapters indicate towards a context dependent implementation of structural flexibility in their local environment. In subsequent chapters, more complex structures are taken under investigation. Chapter 4 deals with integrin αIIbβ3 that is involved in rare genetic disorders. Impact of the pathological mutations on the local flexibility is studied in two rigid domains of integrin αIIbβ3 ectodomain. Inherent flexibility in these domains is shown to modulate the impact of mutations towards the loops. Chapter 5 deals with the structural modelling and dynamics of a more complex protein structure of Duffy Antigen Chemokine Receptor embedded in an erythrocyte mimic membrane system. The model is supported by the most comprehensive phylogenetic analysis on chemokine receptors till date as explained in the last chapter of the thesis.
Efficient video indexing scheme for content-based retrieval

Extracting a small number of key frames that can abstract the content of video is very important for efficient browsing and retrieval in video databases. In this paper, the key frame extraction problem is considered from a set-theoretic point of view, and systematic algorithms are derived to find a compact set of key frames that can represent a video segment for a given degree of fidelity. The proposed extraction algorithms can be hierarchically applied to obtain a tree-structured key frame hierarchy that is a multilevel abstract of the video. The key frame hierarchy enables an efficient content-based retrieval by using the depth-first search scheme with pruning. , Intensive experiments on a variety of video sequences are presented to demonstrate the improved performance of the proposed algorithms over the existing approaches.
New aspects of process and formulation development for freeze-drying of proteins

Drying can significantly improve the stability of protein drugs compared to liquid formulation and mostly, freeze-drying (lyophilisation) is employed for drug products for that respect. However, chemical degradation, like formation of disulfide bonds, oxidation, deamidation or glycation as well as physical instability, conformational or colloidal also occur in the dried state. Due to the complexity of the protein molecules a comprehensive analysis with a multitude of methods such as particle analysis, chromatography, circular dichroism or infrared spectroscopy are necessary. Typical excipients in drying include sugars, polyols or polymers. The two leading hypotheses for their ability to stabilize proteins in the dried state are the water replacement and the immobilization in an amorphous glass. Each step of freezeor spraydrying process like freezing, droplet formation, water removal affects protein stability in different ways. Interfacial related stress occurs in almost all process steps whereas concentration effects are important during freeze-concentration or droplet formation.
A Conserved Sequence within the H2 Subunit of the Vaccinia Virus Entry/Fusion Complex Is Important for Interaction with the A28 Subunit and Infectivity

ABSTRACT The recently described vaccinia virus entry/fusion complex (EFC) comprises at least eight polypeptides that are conserved in all poxviruses. Neither the structure of the complex nor the roles of individual subunits are known. Here we provide evidence for an interaction between the H2 and A28 subunits in the context of a virus infection as well as in uninfected cells transfected with plasmids expressing the corresponding genes. We focused on a highly conserved 21-amino acid-segment in H2 that is flanked by cysteine residues. The effect of amino acid substitutions within the 21-amino-acid segment was determined by an infectivity complementation assay using a conditional H2-null mutant of vaccinia virus. Mutations that had no, moderate, or large negative effects on complementation were found. The latter group included glutamic acid substitutions of leucine and individual glycines and alanine substitution of both glycines within a LGYSG sequence. Mutations with the most pronounced effect on infectivity disrupted the interaction of H2 with A28 to the greatest extent in both infected and uninfected cells. These data indicate that the LGYSG sequence is important for the interaction of H2 with A28 and suggest that this sequence is buried within the EFC complex.
The preclinical pharmacology of mephedrone; not just MDMA by another name

The substituted β‐keto amphetamine mephedrone (4‐methylmethcathinone) was banned in the UK in April 2010 but continues to be used recreationally in the UK and elsewhere. Users have compared its psychoactive effects to those of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’). This review critically examines the preclinical data on mephedrone that have appeared over the last 2–3 years and, where relevant, compares the pharmacological effects of mephedrone in experimental animals with those obtained following MDMA administration. Both mephedrone and MDMA enhance locomotor activity and change rectal temperature in rodents. However, both of these responses are of short duration following mephedrone compared with MDMA probably because mephedrone has a short plasma half‐life and rapid metabolism. Mephedrone appears to have no pharmacologically active metabolites, unlike MDMA. There is also little evidence that mephedrone induces a neurotoxic decrease in monoamine concentration in rat or mouse brain, again in contrast to MDMA. Mephedrone and MDMA both induce release of dopamine and 5‐HT in the brain as shown by in vivo and in vitro studies. The effect on 5‐HT release in vivo is more marked with mephedrone even though both drugs have similar affinity for the dopamine and 5‐HT transporters in vitro. The profile of action of mephedrone on monoamine receptors and transporters suggests it could have a high abuse liability and several studies have found that mephedrone supports self‐administration at a higher rate than MDMA. Overall, current data suggest that mephedrone not only differs from MDMA in its pharmacological profile, behavioural and neurotoxic effects, but also differs from other cathinones.
Approximate Dirichlet Process Computing in Finite Normal Mixtures

A rich nonparametric analysis of the finite normal mixture model is obtained by working with a precise truncation approximation of the Dirichlet process. Model fitting is carried out by a simple Gibbs sampling algorithm that directly samples the nonparametric posterior. The proposed sampler mixes well, requires no tuning parameters, and involves only draws from simple distributions, including the draw for the mass parameter that controls clustering, and the draw for the variances with the use of a nonconjugate uniform prior. Working directly with the nonparametric prior is conceptually appealing and among other things leads to graphical methods for studying the posterior mixing distribution as well as penalized MLE procedures for deriving point estimates. We discuss methods for automating selection of priors for the mean and variance components to avoid over or undersmoothing the data. We also look at the effectiveness of incorporating prior information in the form of frequentist point estimates.
Probabilistic matching pair selection for SURF-based person re-identification

The objective of this paper is to study the performance of human reidentification based on multi-shot SURF and to assess its degradation according to the angular difference between the test and reference video scene view angles. In this context, we propose a new automatic statistical method of acceptance and rejection of SURF correspondence based on the likelihood ratio of two GMMs learned on the reference set and modeling the distribution of distances resulting from matching sequences associated with the same person and with different persons respectively. The experimental results show that our approach compares favorably with the state of the art and achieves a good performance.
Establishing the upper reference limit of Galectin-3 in healthy blood donors

Introduction Galectin-3 (Gal-3) is an independent predictor of poor outcomes and mortality in patients with heart failure (HF). Thus, it has been proposed as a reliable prognostic biomarker for HF. The definition of reference intervals is mandatory for interpreting the findings of experimental studies and encouraging the routine use of biomarkers in clinical practice. To date, no study assessed the reference intervals of Gal-3 and identified the biological variables that affect its concentration in a well-defined healthy population. The aim of this study was to determine the upper reference limit (URL) of Gal-3 in a highly reliable population of healthy subjects. Materials and methods We recruited 714 blood donors. After measuring surrogate biomarkers to identify underlying diseases, 8 subjects were excluded. A final population of 706 individuals (385 men (54.5%); median age 39 (18-65) years) was included. The URL was calculated using the non-parametric percentile approach. Results The 97.5th percentile URL of plasma Gal-3 in our study population (90% CI) was 26.1 (23.3–31.5) ng/mL. After stratifying subjects according to age, the URL of Gal-3 was found to be considerably higher in older (> 45 years) than in younger subjects (31.5 (26.2–51.4) vs 21.8 (21–26.1) ng/mL, respectively). No sex-related differences were found in Gal-3 plasma concentration. Conclusions We established the URL of Gal-3 in a highly selected healthy population. Our findings indicate that age is an important determinant of Gal-3 plasma concentration, so that multiple diagnostic cut-offs should be preferably used according to the different age classes.
Influence of surface treatment on the wear of solid zirconia

Abstract Objective. Recently there has been talk of the use of full-contour solid zirconia crowns or bridge restorations with no porcelain overlay. This could be a useful solution for patients with bruxism or limited interocclusal space. However, the hardness of zirconia could affect the opposite natural dentition. The aim of this in-vitro study was to investigate the role of surface treatments on the wear of a zirconia material and its antagonist. Materials and methods. Fifty plates (10 × 10 × 1 mm) made of zirconia (LavaMulti™ ZrO2, 3M ESPE), divided into five equal groups, were sandblasted and ground under standardized conditions with a fine-grit diamond bur (Komet Brasseler, Germany) to simulate clinical conditions. Group (a) was only fired, (b) was fired and sandblasted, (c) only ground, (d) was ground and additionally polished (EVE Ceramic Polishing-Set, Pforzheim) and (e) was ground and glazed. Wear behavior was measured with a pin-on-disk apparatus ABREX against 6 mm steatite balls as antagonists (45°, 5 N load, 5000 cycles, water). The amount of wear was determined topographically using a 3-D profilometer (Concept 3D, Mahr, Germany) by measuring the height loss of the antagonist and the depth of wear Pt of the zirconia. Results. In groups (a), (b), (c) and (d) the wear value Pt could not be determined (<1 μm). Wear values of the antagonists (steatite balls) revealed a similar outcome in contact with (b), (c) and (e) in the range of 81–85 μm, whereas (e) was more abrasive but not significantly. A noticeable difference in the wear of the antagonist showed group (d) to have the smallest value. Conclusion. Polished zirconia seems to have the lowest wear on the antagonists, in contrast with the other kinds of surface treatment.
Nutrition labels influence value computation of food products in the ventromedial prefrontal cortex

Prevalence of obesity is high in most industrialized nations, and therefore, it is crucial to understand contextual factors underlying food choice. Nutrition labels are public policy interventions designed to adequately inform consumers about nutritional value and overall healthiness of food products. The present study examines how different nutrition labels, namely a purely information‐based label (guideline daily amount, GDA) and a more explicit traffic light (TL) label, influence product valuation and choice in a functional MRI setting.
Beyond pain: modeling decision-making deficits in chronic pain

Risky decision-making seems to be markedly disrupted in patients with chronic pain, probably due to the high cost that impose pain and negative mood on executive control functions. Patients’ behavioral performance on decision-making tasks such as the Iowa Gambling Task (IGT) is characterized by selecting cards more frequently from disadvantageous than from advantageous decks, and by switching often between competing responses in comparison with healthy controls (HCs). In the present study, we developed a simple heuristic model to simulate individuals’ choice behavior by varying the level of decision randomness and the importance given to gains and losses. The findings revealed that the model was able to differentiate the behavioral performance of patients with chronic pain and HCs at the group, as well as at the individual level. The best fit of the model in patients with chronic pain was yielded when decisions were not based on previous choices and when gains were considered more relevant than losses. By contrast, the best account of the available data in HCs was obtained when decisions were based on previous experiences and losses loomed larger than gains. In conclusion, our model seems to provide useful information to measure each individual participant extensively, and to deal with the data on a participant-by-participant basis.
Rufinamide in patients with Lennox-Gastaut syndrome

Objectives: Lennox–Gastaut syndrome (LGS) is an epileptic encephalopathy with an onset at the age of ~ 4 years. LGS is notoriously difficult to manage, as most patients experience multiple seizures per day, despite their concomitant use of several antiepileptic drugs (AEDs). Rufinamide (BANZEL ® ) is an AED approved by the US Food and Drug Administration for the adjunctive treatment of seizures associated with LGS in pediatric patients aged ≥ 1 year and in adults. The expert care of nurses knowledgeable in the treatment options for LGS is valuable to patients and caregivers. This review summarizes the existing knowledge on LGS and data from clinical and real-world studies on the use of rufinamide in patients with LGS. Methods: Recent review articles and information from the Epilepsy Foundation Website were reviewed for data on LGS treatment. Primary articles on rufinamide were also selected for review. Results and conclusion: The efficacy and safety of rufinamide have been evaluated in children and adults by using double-blind, open-label, and observational studies. In general, these studies indicate that rufinamide effectively reduces the frequency and severity of multiple seizure types associated with LGS and has tolerable side effects, the most common being vomiting and somnolence. Dosing modifications based on age, weight, and concomitant AED usage are recommended for patients using rufinamide.
Activation of Coagulation and Fibrinolysis in Acute Respiratory Distress Syndrome: A Prospective Pilot Study

Introduction Coagulation and fibrinolysis remain sparsely addressed with regards to acute respiratory distress syndrome (ARDS). We hypothesized that ARDS development might be associated with changes in plasma coagulation and fibrinolysis. Our aim was to investigate the relationships between ARDS diagnosis and plasma concentrations of tissue factor (TF), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) in mechanically ventilated patients at increased risk of developing ARDS. Materials and methods We performed an ethically approved prospective observational pilot study. Inclusion criteria were patients with PaO2/FiO2 < 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 h, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria were age below 18 years; cardiac disease. We sampled plasma prospectively and compared patients who developed ARDS with those who did not using descriptive statistics and chi-square analysis of baseline demographical and clinical data. We also analyzed plasma concentrations of TF, t-PA, and PAI-1 at inclusion (T0) and on third (T3) and seventh day (T7) of the ICU stay with non-parametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic curve analysis. Statistical significance: p < 0.05. Results Of 24 patients at risk, 6 developed mild ARDS and 4 of each moderate or severe ARDS, respectively, 3 ± 2 (mean ± SD) days after inclusion. Median plasma concentrations of TF and PAI-1 were significantly higher at T7 in patients with ARDS, as compared to non-ARDS. Simultaneously, we found moderate correlations between plasma concentrations of TF and PAI-1, TF and PaO2/FiO2, and positive end-expiratory pressure and TF. TF plasma concentration was associated with ARDS with 71% sensitivity and 100% specificity, a cut off level of 145 pg/ml and AUC 0.78, p = 0.02. PAI-1 displayed 64% sensitivity and 100% specificity with a cut off concentration of 117.5 pg/ml and AUC 0.77, p = 0.02. t-PA did not change significantly during the observation time. Conclusion This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after 7 days in ICU.
Constraint integer programming

This thesis introduces the novel paradigm of constraint integer programming (CIP), which integrates constraint programming (CP) and mixed integer programming (MIP) modeling and solving techniques. It is supplemented by the software SCIP, which is a solver and framework for constraint integer programming that also features SAT solving techniques. SCIP is freely available in source code for academic and non-commercial purposes. Our constraint integer programming approach is a generalization of MIP that allows for the inclusion of arbitrary constraints, as long as they turn into linear constraints on the continuous variables after all integer variables have been fixed. The constraints, may they be linear or more complex, are treated by any combination of CP and MIP techniques: the propagation of the domains by constraint specific algorithms, the generation of a linear relaxation and its solving by LP methods, and the strengthening of the LP by cutting plane separation. The current version of SCIP comes with all of the necessary components to solve mixed integer programs. In the thesis, we cover most of these ingredients and present extensive computational results to compare different variants for the individual building blocks of a MIP solver. We focus on the algorithms and their impact on the overall performance of the solver. In addition to mixed integer programming, the thesis deals with chip design verification, which is an important topic of electronic design automation. Chip manufacturers have to make sure that the logic design of a circuit conforms to the specification of the chip. Otherwise, the chip would show an erroneous behavior that may cause failures in the device where it is employed. An important subproblem of chip design verification is the property checking problem, which is to verify whether a circuit satisfies a specified property. We show how this problem can be modeled as constraint integer program and provide a number of problem-specific algorithms that exploit the structure of the individual constraints and the circuit as a whole. Another set of extensive computational benchmarks compares our CIP approach to the current state-of-the-art SAT methodology and documents the success of our method.
A Review: Recent Progress on Evaluation of Flowability and Floodability of Powder

Recent studies evaluating the flowability and floodability of cohesive powder under conditions of consolidation, mechanical force, vibrating force, fluid force, and floodability are reviewed. The ball indentation test is an effective method for evaluating the flowability of a small amount of cohesive powder at very low stress under consolidation conditions. The environmental conditions such as temperature and humidity play an important role in the flow of cohesive powder. With regard to cohesive powder flowing under mechanical force, the FT4 powder rheometer can evaluate the powder flowability using the total energy which is related to the shear stress on the impeller blade. The vibrating capillary method and the vibrating shear tube method are effective for the measurement of the flowability of strongly cohesive powder. The test using powder discharge by air flow can assess the flowability of cohesive powder which Carr’s flowability index is an equivalent level by using mass flow rate and interstitial air pressure. Finally, the flushing of cohesive powder occurs when the interstitial air pressure and the void fraction are high. The pressure difference between the interstitial air pressure and the outside of an orifice are the dominant factors in the spouting of powder.
Abax: 2D/3D legaliser supporting look-ahead legalisation and blockage strategies

Abax is a modern version of the classical Abacus, minimum displacement, greedy legaliser. Abax supports single-tier 2D or 3D legalisation for multiple, logic-on-logic 3D-IC tiers, efficient look-ahead legalisation of intermediate Global Placement (GP) iterations, Hard Macros, Blockages, row density constraints and multiple local cell displacement functions and cell orderings. For 3D-IC, Abax can produce multi-tier 3D-IC placements by performing Legalisation-based Partitioning. For efficient Look-ahead Legalisation, Abax supports two new local displacement cost functions, multi-cell mean and multi-cell total. We show that the classical single-cell displacement and multi-cell total can result in artifacts when legalising early intermediate GPs, and that multi-cell mean is the best candidate for Look-ahead Legalisation. Obstructions, i.e. Hard Macros and Blockages are handled by using two strategies. We present legalisation results for the ISPD2014 and ISPD2015 benchmarks, by using GP generated from Eh? Placer, and HPWL measurement by using RippleDP. For 3D, two-tier legalisation we illustrate a ∼30% reduction in HPWL for a set of ISPD2014 benchmarks. For 2D legalisation on the ISPD2015 benchmarks, our average HPWL increase over GP is 3.03%, compared to 7.21% of the Eh? Placer legaliser, and 43.16% of the RippleDP legaliser.
Cognitive impairment in ICU survivors: Assessment and therapy

Cognitive impairment occurs in up to one-third of intensive care patients and may affect one or more cognitive domains. Because data are scarce on therapies for this complication, prevention remains the prevailing strategy. In this review, we discuss the clinical approach to cognitive impairment after an intensive care unit (ICU) stay. Cognitive impairment occurs in up to one-third of patients after a stay in the intensive care unit. Prevention is the prevailing strategy, since data on treatment are scarce.