Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved tumor targeting of anti–epidermal growth factor receptor Nanobodies through albumin binding: taking advantage of modular Nanobody technology

The ∼15-kDa variable domains of camelid heavy-chain-only antibodies (called Nanobodies) can easily be formatted as multivalent or multispecific single-chain proteins. Because of fast excretion, however, they are less suitable for therapy of cancer. In this study, we aimed for improved tumor targeting of a bivalent anti–epidermal growth factor receptor (EGFR) Nanobody (αEGFR-αEGFR) by fusion to a Nanobody unit binding to albumin (αAlb). Biodistributions of αEGFR-αEGFR, αEGFR-αEGFR-αAlb (∼50 kDa), αTNF-αTNF-αAlb (control, binding tumor necrosis factor-α), and the ∼150-kDa anti-EGFR antibody cetuximab were compared in A431 xenograft-bearing mice. The proteins were radiolabeled with 177Lu to facilitate quantification. Tumor uptake of 177Lu-αEGFR-αEGFR decreased from 5.0 ± 1.4 to 1.1 ± 0.1 %ID/g between 6 and 72 h after injection. Due to its rapid blood clearance, tumor-to-blood ratios >80 were obtained within 6 h after injection. Blood clearance became dramatically slower and tumor uptake became significantly higher by introduction of αAlb. Blood levels of αEGFR-αEGFR-αAlb were 21.2 ± 2.5, 11.9 ± 0.6, and 4.0 ± 1.4 and tumor levels were 19.4 ± 5.5, 35.2 ± 7.5, and 28.0 ± 6.8 %ID/g at 6, 24, and 72 h after injection, respectively. Tumor uptake was at least as high as for cetuximab (15.5 ± 3.9, 27.1 ± 7.9, and 25.6 ± 6.1 %ID/g) and significantly higher than for αTNF-αTNF-αAlb. αEGFR-αEGFR-αAlb showed faster and deeper tumor penetration than cetuximab. These data show that simple fusion of αEGFR and αAlb building blocks results in a bifunctional Nanobody format, which seems more favorable for therapy as far as pharmacokinetics and tumor deposition are concerned. [Mol Cancer Ther 2008;7(8):2288–97]
Trace gas and particle emissions from domestic and industrial biofuel use and garbage burning in central Mexico

In central Mexico during the spring of 2007 we measured the initial emissions of 12 gases and the aerosol speciation for elemental and organic carbon (EC, OC), anhy- drosugars, Cl , NO 3 , and 20 metals from 10 cooking fires, four garbage fires, three brick making kilns, three charcoal making kilns, and two crop residue fires. Global biofuel use has been estimated at over 2600 Tg/y. With several simple case studies we show that cooking fires can be a major, or the major, source of several gases and fine particles in devel- oping countries. Insulated cook stoves with chimneys were earlier shown to reduce indoor air pollution and the fuel use per cooking task. We confirm that they also reduce the emis- sions of VOC pollutants per mass of fuel burned by about half. We did not detect HCN emissions from cooking fires in Mexico or Africa. Thus, if regional source attribution is based on HCN emissions typical for other types of biomass burning (BB), then biofuel use and total BB will be under- estimated in much of the developing world. This is also sig- nificant because cooking fires are not detected from space. We estimate that 2000 Tg/y of garbage are generated glob- ally and about half may be burned, making this a commonly overlooked major global source of emissions. We estimate a fine particle emission factor (EFPM 2.5) for garbage burning of 10.5±8.8 g/kg, which is in reasonable agreement with very limited previous work. We observe large HCl emission factors in the range 2-10 g/kg. Consideration of the Cl con- tent of the global waste stream suggests that garbage burning
Synthesis of New Quinoxalines Containing an Oxirane Ring by the TDAE Strategy and in Vitro Evaluation in Neuroblastoma Cell Lines

Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. In order to obtain new compounds active on neuroblastoma cell lines, we investigated the reactivity of carbanion formed via TDAE in quinoxaline series. The new synthesized compounds were tested for their anti-proliferative activity on two neuroblastoma cell lines, and seven oxirane derivatives obtained interesting activities.
Hierarchical Feature Pooling with Structure Learning: A New Method for Pedestrian Detection

Objects such as pedestrians exhibit large intra-class variations, posing significant challenges for visual object detection. State-of-the-art part-based models explicitly model object deformations, but are limited in their ability to handle image variations incurred by other geometric and photometric changes, such as human pose, lighting, occlusions, and large appearance variations. In this paper, we propose a novel approach which uses a spatially-biased hierarchical scheme to map features into a high-dimensional space that better represents the rich set of object appearance and local deformation variations. We propose a new algorithm to jointly learn the classification function and feature pooling in this high-dimensional space, in a structured prediction setting. Our approach achieves the best detection performance on the INRIA pedestrian dataset.
The SAMMIE System: Multimodal In-Car Dialogue

The SAMMIE system is an in-car multi-modal dialogue system for an MP3 application. It is used as a testing environment for our research in natural, intuitive mixed-initiative interaction, with particular emphasis on multimodal output planning and realization aimed to produce output adapted to the context, including the driver's attention state w.r. t. the primary driving task.
Confirmation of a Positive Association between Prostate Cancer Risk and a Locus at Chromosome 8q24

Background: Family-based linkage studies, association studies, and studies of tumors have highlighted human chromosome 8q as a genomic region of interest for prostate cancer susceptibility loci. Recently, a locus at 8q24, characterized by both a single nucleotide polymorphism (SNP) and a microsatellite marker, was shown to be associated with prostate cancer risk in Icelandic, Swedish, and U.S. samples. Although the data were provocative, the U.S. samples were not population based, which precludes assessment of the potential contribution of this locus to prostate cancer incidence in the United States. Methods: We analyzed both markers in a population-based, case-control study of middle-aged men from King County, Washington. Results: Overall, there was a significant positive association between the A allele of the SNP rs1447295 and prostate cancer risk [odds ratio, 1.4; 95% confidence interval (95% CI), 1.1-2.0] but no significant association with the microsatellite DG8S737. However, significant associations were observed for both markers in men with high Gleason scores. Adjusting for age, first-degree family history of prostate cancer, and prostate cancer screening history, the adjusted odds ratios were 1.4 (95% CI, 1.1-1.8) for the A allele of the SNP and 1.9 (95% CI, 1.2-2.8) for the −10 allele of the microsatellite. Conclusions: These data suggest that the locus on chromosome 8q24 harbors a genetic variant associated with prostate cancer and that the microsatellite marker is a stronger risk factor for aggressive prostate cancers defined by poorly differentiated tumor morphology. (Cancer Epidemiol Biomarkers Prev 2007;16(4):809–14)
Reduction of l-DOPA-Induced Dyskinesia by the Selective Metabotropic Glutamate Receptor 5 Antagonist 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]pyridine in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Lesioned Macaque Model of Parkinson's Disease

Long-term motor complications of dopamine replacement, such as l-DOPA-induced dyskinesia (LID) and reduced quality of l-DOPA action, remain obstacles in the treatment of Parkinson's disease. Dysfunctional glutamatergic neurotransmitter systems have been observed in both the untreated parkinsonian and dyskinetic states and represent novel targets for treatment. Here, we assess the pharmacokinetic profile and corresponding pharmacodynamic effects on behavior of the orally active, selective metabotropic glutamate receptor type 5 (mGlu5) antagonist, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) (as the hydrochloride salt) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned macaque. Six parkinsonian, MPTP-lesioned cynomolgus monkeys, with established LID, were administered acute challenges with MTEP (4.5–36 mg/kg p.o.) or vehicle, either alone or in combination with l-DOPA (33 ± 1 mg/kg p.o.). Motor activity, parkinsonian disability, and dyskinesia were assessed for a 6-h period. Plasma drug levels were assessed by liquid chromatography-tandem mass spectrometry. MTEP had no antiparkinsonian action as monotherapy. However, administration of l-DOPA in combination with MTEP (36 mg/kg) reduced peak dose LID by 96%. Moreover, although total on-time (duration for which l-DOPA exerted an antiparkinsonian effect) was not significantly reduced, MTEP (36 mg/kg) reduced the duration of on-time with disabling LID by 70% compared with that for l-DOPA alone. These effects were associated with a peak plasma concentration of 20.9 μM and an area under the curve from 0 to 24 h of 136.1 h · μM (36 mg/kg). Although total on-time was not reduced, the peak antiparkinsonian benefit of l-DOPA/MTEP (36 mg/kg) was less than that with l-DOPA alone. Selective mGlu5 inhibitors may have significant potential to ameliorate dyskinesia, but care should be taken to ensure that such effects do not come at the expense of the peak antiparkinsonian benefit of l-DOPA.
Emerging Paradigms for the Initiation of Mucin-type Protein O-Glycosylation by the Polypeptide GalNAc Transferase Family of Glycosyltransferases*

Mammalian mucin-type O-glycosylation is initiated by a large family of ∼20 UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferases (ppGalNAc Ts) that transfer α-GalNAc from UDP-GalNAc to Ser and Thr residues of polypeptide acceptors. Characterizing the peptide substrate specificity of each isoform is critical to understanding their properties, biological roles, and significance. Presently, only the specificities of ppGalNAc T1, T2, and T10 and the fly orthologues of T1 and T2 have been systematically characterized utilizing random peptide substrates. We now extend these studies to ppGalNAc T3, T5, and T12, transferases variously associated with human disease. Our results reveal several common features; the most striking is the similar pattern of enhancements for the three residues C-terminal to the site of glycosylation for those transferases that contain a common conserved Trp. In contrast, residues N-terminal to the site of glycosylation show a wide range of isoform-specific enhancements, with elevated preferences for Pro, Val, and Tyr being the most common at the −1 position. Further analysis reveals that the ratio of positive (Arg, Lys, and His) to negative (Asp and Glu) charged residue enhancements varied among transferases, thus further modulating substrate preference in an isoform-specific manner. By utilizing the obtained transferase-specific preferences, the glycosylation patterns of the ppGalNAc Ts against a series of peptide substrates could roughly be reproduced, demonstrating the potential for predicting isoform-specific glycosylation. We conclude that each ppGalNAc T isoform may be uniquely sensitive to peptide sequence and overall charge, which together dictates the substrate sites that will be glycosylated.
Evolutionary Robotics and the Radical Envelope-of-Noise Hypothesis

For several years now, various researchers have endeavored to apply artificial evolution to the automatic design of control systems for real robots. One of the major challenges they face concerns the question of how to assess the fitness of evolving controllers when each evolutionary run typically involves hundreds of thousands of such assessments. This article outlines new ways of thinking about and building simulations upon which such assessments can be performed. It puts forward sufficient conditions for the successful transfer of evolved controllers from simulation to reality and develops a potential methodology for building simulations in which evolving controllers are forced to satisfy these conditions if they are to be reliably fit. It is hypothesized that as long as simulations are built according to this methodology, it does not matter how inaccurate or incomplete they are: Controllers that have evolved to be reliably fit in simulation still will transfer into reality. Two sets of experiments are reported, both of which involve minimal look-up table-based simulations built according to these guidelines. In the first set, controllers were evolved that allowed a Khepera robot to perform a simple memory task in the real world. In the second set, controllers were evolved for the Sussex University gantry robot that were able to distinguish visually a triangle from a square, under extremely noisy real-world conditions, and to steer the robot toward the triangle. In both cases, controllers that were reliably fit in simulation displayed extremely robust behavior when downloaded into reality.
Solving Geometric Optimization Problems using Graphics Hardware

We show how to use graphics hardware for tackling optimization problems arising in the field of computationalgeometry. We exemplarily discuss three problems, where combinatorial algorithms are inefficient or hard to implement.Given a set S of n point in the plane, the first two problems are to determine the smallest homotheticscaling of a star shaped polygon P enclosing S and to find the largest empty homothetic scaling of P completelycontained inside an arbitrary polygonal region. Pixel‐exact solutions for both problems are computed in real‐time.The third problem is a facility location problem and more difficult to solve. Given the Voronoi diagram VoD(S) ofthe n points, we try to position another point p in the plane, such that the resulting Voronoi region of p has maximalarea. As far as we know there exists no traditional solution for this problem for which we present pixel‐exactsolutions.
An Infornation-Theoretic Analysis of Relational Databases&#8212;Part I: Data Dependencies and Information Metric

Database design is based on the concept of data dependency, which is the interrelationship between data contained in various sets of attributes. In particular, functional, multivalued and acyclic join, dependencies play an essential role in the design of database schemas. The basic definition of an information metric and how this notion can be used in relational database are discussed in this paper. We use Shannon entropy as an information metric to quantify the information associated with a set of attributes. Thus, we prove that data dependencies can be formulated in terms of entropies. These formulas make the numerical computation and testing of data dependencies feasible. Among the different types of data dependencies, the acyclic join dependency is most important to the design of a relational database schema. The acyclic join dependency, with multivalued dependency as a special case, impose a constraint on the information-preserving decomposition of a relation. It is interesting that this constraint on a relation is similar to Gibbs' condition for separating physical systems in statistical mechanics. They both assert that entropy is preserved during the decomposition process. That is, the entropies of the corresponding set of attributes must satisfy the inclusion–exclusion identity.
MMSE filtering for amplify & forward simo multiple access channel with ill-conditioned second hop

Relaying has been extensively studied during the last decades and has found numerous applications in wireless communications. The simplest relaying method, namely amplify and forward, has shown potential in MIMO multiple access systems, when Gaussian fading channels are assumed for both hops. However, in some cases ill conditioned channels may appear on the second hop. For example, this impairment could affect cooperative BS systems with microwave link backhauling, which involves strong line of sight channels with insufficient scattering. In this paper, we consider a large system analysis of such as system model focusing on the joint MMSE filtering receiver. Analytical methods based on free probability are presented for calculating the MMSE error and average SINR, while the performance degradation of the system throughput due to second hop ill-conditioning is studied.
Predictable behavior during contact simulation: a comparison of selected physics engines

Contact behaviors in physics simulations are important for real‐time interactive applications, especially in virtual reality applications where user's body parts are tracked and interact with the environment via contact. For these contact simulations, it is ideal to have small changes in initial condition yield predictable changes in the output. Predictable simulation is key for success in iterative learning processes as well, such as learning controllers for manipulations or locomotion tasks. Here, we present an extensive comparison of contact simulations using Bullet Physics, Dynamic Animation and Robotics Toolkit (DART), MuJoCo, and Open Dynamics Engine, with a focus on predictability of behavior. We first tune each engine to match an analytical solution as closely as possible and then compare the results for a more complex simulation. We found that in the commonly available physics engines, small changes in initial condition can sometimes induce different sequences of contact events to occur and ultimately lead to a vastly different result. Our results confirmed that parameter settings do matter a great deal and suggest that there may be a trade‐off between accuracy and predictability. Copyright © 2016 John Wiley & Sons, Ltd.
Cloning and nucleotide sequence of the Salmonella typhimurium dcp gene encoding dipeptidyl carboxypeptidase

Plasmids carrying the Salmonella typhimurium dcp gene were isolated from a pBR328 library of Salmonella chromosomal DNA by screening for complementation of a peptide utilization defect conferred by a dcp mutation. Strains carrying these plasmids overproduced dipeptidyl carboxypeptidase approximately 50-fold. The nucleotide sequence of a 2.8-kb region of one of these plasmids contained an open reading frame coding for a protein of 77,269 Da, in agreement with the 80-kDa size for dipeptidyl carboxypeptidase (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration). The N-terminal amino acid sequence of dipeptidyl carboxypeptidase purified from an overproducer strain agreed with that predicted by the nucleotide sequence. Northern (RNA) blot data indicated that dcp is not cotranscribed with other genes, and primer extension analysis showed the start of transcription to be 22 bases upstream of the translational start. The amino acid sequence of dcp was not similar to that of a mammalian dipeptidyl carboxypeptidase, angiotensin I-converting enzyme, but showed striking similarities to the amino acid sequence of another S. typhimurium peptidase encoded by the opdA (formerly optA) gene.
Group treatment for trichotillomania: cognitive-behavioral therapy versus supportive therapy.

OBJECTIVE Trichotillomania is a psychiatric condition characterized by the chronic pulling and plucking of one's own hair. Cognitive-behavioral therapy shows promise as a treatment for trichotillomania and might be preferable to pharmacotherapy. However, there have been no randomized, controlled studies of the efficacy of group cognitive-behavioral therapy. METHOD We evaluated 44 subjects, recruited from April 2009 to May 2010, all of whom met DSM-IV criteria for a diagnosis of trichotillomania. Subjects were randomized to receive 22 sessions of either group cognitive-behavioral therapy or group supportive therapy (control). Treatment evaluation was non-blind and used self-report scales. The primary outcome measure was the improvement of hair-plucking behavior as assessed by the Massachusetts General Hospital Hairpulling Scale. Secondary measures included scores on the Beck Depression Inventory, the Beck Anxiety Inventory, and the Social Adjustment Scale-Self-Report. RESULTS Both groups showed significant posttreatment improvement in the scores from the Massachusetts General Hospital Hairpulling Scale (F = 23.762, P < .001) and the Beck Depression Inventory (F = 6.579, P = .003). The decrease in hair-plucking behavior over time was significantly greater in the study group than in the control group (F = 3.545, P < .038). There were no significant differences between the pretreatment and posttreatment time points or between the groups in the scores from the Beck Anxiety Inventory and the Social Adjustment Scale-Self-Report. CONCLUSIONS We conclude that group cognitive-behavioral therapy is a valid treatment for trichotillomania. This treatment model should be further revised and expanded to address comorbidities such as anxiety and social maladjustment. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01968343.
Paternal effects in Arabidopsis indicate that offspring can influence their own size

The existence of genetic variation in offspring size in plants and animals is puzzling because offspring size is often strongly associated with fitness and expected to be under stabilizing selection. An explanation for variation in seed size is conflict between parents and between parents and offspring. However, for this hypothesis to be true, it must be shown that the offspring genotype can affect its own size. The existence of paternal effects would support this hypothesis, but these have rarely been shown. Using a diallel cross among four natural accessions of Arabidopsis thaliana we show that maternal, paternal and positional effects jointly influence seed size, number and the frequency of seed abortion. We found that seed abortion (%) depends on the combination of maternal and paternal genotypes, suggesting the existence of mate choice or epistatic incompatibility among accessions of A. thaliana. In addition, since paternal genotype explains approximately 10 per cent of the variation in seed size, we propose that A. thaliana's offspring must influence the amount of resources allocated to themselves. Identification of paternal effects in Arabidopsis should facilitate dissection of the genetic mechanisms involved in paternal effects.
Physiological maturity of seeds and colorimetry of fruits of Jatropha curcas L.

The objective was to relate the coloration of fruits of Jatropha curcas L during the maturation process with morphometric (fruits and seeds) and germinative characteristics (seeds). Fruits were collected at various maturation stages from mast trees located in Eldorado/MS, and six maturation stages were visually classified based on fruit's epicarp color. Epicarp digital colorimetry was used to characterize maturation stages in addition to morphometric variables of length and width of fruits and seeds, as well their water content. For determining the physiological potential it was used germination test, emergence velocity index and first count of germination. Results indicated that seeds of J. curcas should be harvested when fruit epicarp shows a reading equal or smaller than 82, 70 or 65 nm of red, green or blue scales from a digital color analyzer. Seeds of fruits with that colorimetry can be harvested in virtue of the maxim acumululation of dry mass, water content below 38,5% and higher physiological potential.