Miracle-dz/UniFAR-FTUs huggingface dataset:
The pearl necklace model in protein A chromatography: Molecular mechanisms at the resin interface

Staphylococcal protein A chromatography is an established core technology for monoclonal antibody purification and capture in the downstream processing. MabSelect SuRe involves a tetrameric chain of a recombinant form of the B domain of staphylococcal protein A, called the Z‐domain. Little is known about the stoichiometry, binding orientation, or preferred binding. We analyzed small‐angle X‐ray scattering data of the antibody–protein A complex immobilized in an industrial highly relevant chromatographic resin at different antibody concentrations. From scattering data, we computed the normalized radial density distributions. We designed three‐dimensional (3D) models with protein data bank crystallographic structures of an IgG1 (the isoform of trastuzumab, used here; Protein Data Bank: 1HZH) and the staphylococcal protein A B domain (the native form of the recombinant structure contained in MabSelect SuRe resin; Protein Data Bank: 1BDD). We computed different binding conformations for different antibody to protein A stoichiometries (1:1, 2:1, and 3:1) and compared the normalized radial density distributions computed from 3D models with those obtained from the experimental data. In the linear range of the isotherm we favor a 1:1 ratio, with the antibody binding to the outer domains in the protein A chain at very low and high concentrations. In the saturation region, a 2:1 ratio is more likely to occur. A 3:1 stoichiometry is excluded because of steric effects.
MAPK/ERK pathway inhibition is a promising treatment target for adrenocortical tumors

Unraveling molecular mechanisms that regulate tumor development and proliferation is of the utmost importance in the quest to decrease the high mortality rate of adrenocortical carcinomas (ACC). Our aim was to evaluate the role of two of the mitogen‐activated protein kinase (MAPK) signaling pathways (extracellular signal‐regulated protein kinases [ERKs 1/2] and p38) in the adrenocortical tumorigenesis, as well as the therapeutic potential of MAPK/ERK inhibition. ERKs 1/2 and p38 activation were evaluated in incidentalomas (INC; n = 10), benign Cushing's syndrome (BCS; n = 12), malignant Cushing's syndrome (MCS; n = 6) and normal adrenal glands (NAG; 8). ACC cell line (H295R) was used to evaluate the ability of PD184352 (0.1, 1, and 10 µM), a specific MEK‐MAPK‐ERK pathway inhibitor, to modulate cell proliferation, viability, metabolism, and steroidogenesis. ERKs 1/2 activation was significantly higher in MCS (2.83 ± 0.17) compared with NAG (1.00 ± 0.19 “arbitrary units”), INC (1.20 ± 0.13) and BCS (2.09 ± 0.09). Phospho‐p38 expression was absent in all the MCS analyzed. MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK‐MAPK‐ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC.
Lifespan Kras mutation levels in lung and liver of B6C3F1 mice

Somatic mutations accumulate in the human genome and are correlated with increased cancer incidence as humans age. The standard model for studying the carcinogenic effects of exposures for human risk assessment is the rodent 2‐year carcinogenicity assay. However, there is little information regarding the effect of age on cancer‐driver gene mutations in these models. The mutant fraction (MF) of Kras codon 12 GGT to GAT and GGT to GTT mutations, oncogenic mutations orthologous between humans and rodents, was quantified over the lifespan of B6C3F1 mice. MFs were measured in lung and liver tissue, organs that frequently develop tumors following carcinogenic exposures. The MFs were evaluated at 4, 6, 8, 12, 21, and 85 weeks, with the 12‐week and 21‐week time points being coincident with the conclusion of 28‐day and 90‐day exposure durations used in short‐term toxicity testing. The highly sensitive and quantitative Allele‐specific Competitive Blocker PCR (ACB‐PCR) assay was used to quantify the number of mutant Kras codon 12 alleles. The mouse lung showed a slight, but significant trend increase in the Kras codon 12 GAT mutation over the 85‐week period. The trend with age can be equally well‐fit by several non‐linear functions, but not by a linear function. In contrast, the liver GAT mutation did not increase, and the GTT mutation did not increase for either organ. Even with the slight increase in the lung GAT MFs, our results indicate that the future use of Kras mutation as a biomarker of carcinogenic effect will not be confounded by animal age. Environ. Mol. Mutagen. 59:715–721, 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
Electric-Acoustic Stimulation Outcomes in Children.

OBJECTIVES This study investigates outcomes in children fit with electric-acoustic stimulation (EAS) and addresses three main questions: (1) Are outcomes with EAS superior to outcomes with conventional electric-only stimulation in children? (2) Do children with residual hearing benefit from EAS and conventional electric-only stimulation when compared with the preoperative hearing aid (HA) condition? (3) Can children with residual hearing derive benefit from EAS after several years of listening with conventional electric-only stimulation? DESIGN Sixteen pediatric cochlear implant (CI) recipients between 4 and 16 years of age with an unaided low-frequency pure tone average of 75 dB HL in the implanted ear were included in two study arms. Arm 1 included new recipients, and Arm 2 included children with at least 1 year of CI experience. Using a within-subject design, participants were evaluated unilaterally with the Consonant-Nucleus-Consonant (CNC) word list in quiet and the Baby Bio at a +5 dB SNR using an EAS program and a conventional full electric (FE) program. Arm 1 participants' scores were also compared with preoperative scores. RESULTS Speech perception outcomes were statistically higher with the EAS program than the FE program. For new recipients, scores were significantly higher with EAS than preoperative HA scores for both the CNC and Baby Bio in noise; however, after 6 months of device use, results in the FE condition were not significantly better than preoperative scores. Long-term FE users benefited from EAS over their FE programs based on CNC word scores. CONCLUSIONS Whether newly implanted or long-term CI users, children with residual hearing after CI surgery can benefit from EAS. Cochlear implantation with EAS fitting is a viable option for children with HAs who have residual hearing but have insufficient access to high-frequency sounds and poor speech perception.
Reliability and Validity of the Minnesota Multiphasic Personality Inventory – 2 – Restructured Form (MMPI-2-RF) in Spine Surgery and Spinal Cord Stimulator Samples

Abstract It is not uncommon for patients to report diminished outcomes as a result of spine surgery or a spinal cord stimulator implant. Presurgical psychological evaluations are increasingly used to identify patients at increased risk for such outcomes and use of personality assessment instruments in these evaluations provides incremental information beyond a clinical interview and medical chart review. This investigation explores the psychometric properties of the Minnesota Multiphasic Personality Inventory–2–Restructured Form (MMPI–2–RF) in a sample of spine surgery patients (n = 810) and in a sample of spinal cord stimulator patients (n = 533). Results indicated that MMPI–2–RF substantive scale scores are reliable, with evidence of good convergent and discriminant validity in both samples. Incorporating the MMPI–2–RF as part of the presurgical evaluation of spine surgery and spinal cord stimulator patients can provide meaningful insight into patients’ functioning and help guide pre- and postsurgical treatment in these settings.
Systematic in vivo study of NiO nanowires and nanospheres: biodegradation, uptake and biological impacts

Abstract High aspect ratio nanomaterials (NM) have a promising future in medicine and industry as a unique category of NM. Consequently, it is important to evaluate their potential biological side-effects before crediting their use. To understand the mechanisms of degradation, internalisation, and interaction with different biological targets, we used the in vivo model Drosophila melanogaster to obtain a systematic and complete study on high aspect ratio Ni nanowires (NiNW), compared with low aspect ratio Ni nanospheres (NiNS), and NiSO4 as a model of agent releasing nickel ions. The distinguished shape of nanowires showed changes in their characteristics after oral administration until they reached the intestinal lumen, where their diameter decreased significantly. For the first time, we confirmed the internalization of needle-shaped materials via perforation of the intestinal barrier. Moreover, the results showed that D. melanogaster is a valid and effective tool in studies related to magnetic resonance imaging (MRI). Additionally, NiNM induced DNA damage and molecular changes at the gene expression level, in association with increase in oxidative stress levels. Notably, the observed negative effects were related to nickel as a metal rather than to its shape, since the effects induced by the three Ni forms were notably similar. In addition, independent of their form, Ni compounds did not induce toxic or mutagenic impacts. Our Drosophila model can be used to understand different phenomena related to high aspect ratio NM exposure, such as degradation, internalization and interaction with different targets.
Biomechanical Material Characterization of Stanford Type-B Dissected Porcine Aortas

Aortic dissection (AD) involves tearing of the medial layer, creating a blood-filled channel called false lumen (FL). To treat dissections, clinicians are using endovascular therapy using stent grafts to seal the FL. This procedure has been successful in reducing mortality but has failed in completely re-attaching the torn intimal layer. The use of computational analysis can predict the radial forces needed to devise stents that can treat ADs. To quantify the hyperelastic material behavior for therapy development, we harvested FL wall, true lumen (TL) wall, and intimal flap from the middle and distal part of five dissected aortas. Planar biaxial testing using multiple stretch protocols were conducted on tissue samples to quantify their deformation behavior. A novel non-linear regression model was used to fit data against Holzapfel–Gasser–Ogden hyperelastic strain energy function. The fitting analysis correlated the behavior of the FL and TL walls and the intimal flap to the stiffness observed during tensile loading. It was hypothesized that there is a variability in the stresses generated during loading among tissue specimens derived from different regions of the dissected aorta and hence, one should use region-specific material models when simulating type-B AD. From the data on material behavior analysis, the variability in the tissue specimens harvested from pigs was tabulated using stress and coefficient of variation (CV). The material response curves also compared the changes in compliance observed in the FL wall, TL wall, and intimal flap for middle and distal regions of the dissection. It was observed that for small stretch ratios, all the tissue specimens behaved isotropically with overlapping stress–stretch curves in both circumferential and axial directions. As the stretch ratios increased, we observed that most tissue specimens displayed different structural behaviors in axial and circumferential directions. This observation was very apparent in tissue specimens from mid FL region, less apparent in mid TL, distal FL, and distal flap tissues and least noticeable in tissue specimens harvested from mid flap. Lastly, using mixed model ANOVAS, it was concluded that there were significant differences between mid and distal regions along axial direction which were absent in the circumferential direction.
Deep Reinforcement Learning from Expert ’ s Experience Replay

Experience replay (ER) [Lin (1993)] serves as a way for online reinforcement learning agents to remember past experiences, and learn from them in future times. Experience replay plays an important role in state of the art architectures in the field of deep reinforcement learning, such as the vanilla DQN [Mnih et al. (2015)]. In this work, we explore how the ER’s attributes, such as the size and amount of exploration within it, affect the learning quality. In addition, we investigate the effect of dynamic data sets, which are common in RL domains, on the learning process. We use ER generated by a teacher, or an expert, agent for instructing a student agent. We conducted our experiments on two domains: MNIST digits classification and Atari 2600, where we have tested on the games Road Runner and Breakout. We propose that both, the diversity of policies used for generating the ER and the size of the ER, have strong correlation with the agent’s performance, such that larger ER that contain more exploration are preferable. Moreover, we show that the neural network’s weights, which represents the agent policy, diverge, after certain amount of learning steps, when using immutable ER. Finally, we show that an RL agent that is taught from an expert’s experience can generalize well.
Support for Learning Büchi Automata and Linear Temporal Logic 1

We introduce a graphical interactive tool, named GOAL, that can assist the user in understanding Büchi automata, linear temporal logic, and their relation. Büchi automata and linear temporal logic are closely related and have long served as fundamental building blocks of linear-time model checking. Understanding their relation is instrumental in discovering algorithmic solutions to model checking problems or simply in using those solutions, e.g., specifying a temporal property directly by an automaton rather than a temporal formula so that the property can be verified by an algorithm that operates on automata. One main function of the GOAL tool is translation of a temporal formula into an equivalent Büchi automaton that can be further manipulated visually. The user may edit the resulting automaton, attempting to optimize it, or simply run the automaton on some inputs to get a basic understanding of how it operates. GOAL includes a large number of translation algorithms, most of which support past temporal operators. With the option of viewing the intermediate steps of a translation, the user can quickly grasp how a translation algorithm works. The tool also provides various standard operations and tests on Büchi automata, in particular the equivalence test which is essential for checking if a hand-drawn automaton is correct in the sense that it is equivalent to some intended temporal formula or reference automaton. Several use cases are elaborated to show how these GOAL functions may be combined to facilitate the learning and teaching of Büchi automata and linear temporal logic.
EFFECT OF HIGH FREQUENCY ULTRASOUNDS ON LYCOPENE AND TOTAL PHENOLIC CONCENTRATION , ANTIOXIDANT PROPERTIES AND α-GLUCOSIDASE INHIBITORY ACTIVITY OF TOMATO JUICE

Tomato juice was subjected to high frequency ultrasounds (378 and 583 kHz) at increasing energy densities (up to 250 MJ/m3). Results relevant to the treatments at high frequency providing an energy density of 250 MJ/m3 were compared with those obtained at 24 kHz delivering the same energy density. Lycopene and total phenolic concentration, as well as the α-glucosidase inhibitory activity of tomato juice, were not affected by ultrasound regardless the frequency and energy density. However, the antioxidant properties were negatively affected by high frequency ultrasounds.
Early Stimulation and Nutrition: The Impacts of a Scalable Intervention

Abstract Early childhood development is becoming the focus of policy worldwide. However, the evidence on the effectiveness of scalable models is scant, particularly when it comes to infants in developing countries. In this paper, we describe and evaluate with a cluster-Randomized Controlled Trial an intervention designed to improve the quality of child stimulation within the context of an existing parenting program in Colombia, known as FAMI. The intervention improved children’s development by 0.16 of a standard deviation (SD) and children’s nutritional status, as reflected in a reduction of 5.8 percentage points of children whose height-for-age is below -1 SD.
New Somatic Hybrid Rootstock Candidates for Tree-size Control and High Juice Quality

New citrus production systems that feature high density plantings being developed and adapted for Florida growing conditions will require improved tree-size controlling rootstocks that bear early and produce good yields of fruit with juice of high quality. Flying Dragon [Poncirus trifoliata(L.) Raf. ], the standard dwarfing stock of the industry, grows slowly in the nursery and generally does not yield adequately. Improved alternative rootstock choices are desirable. Tetraploid rootstocks, both autotetraploids and allotetraploids, have been shown to have a capacity to reduce tree size when budded with commercial diploid scions. We have been exploring somatic hybridization of complementary diploid rootstocks via protoplast fusion to generate allotetraploid rootstock candidates for many years. Our early work featured production of somatic hybrids of many complementary rootstock combinations, including hybrids of sweet orange and mandarins with Flying Dragon. Field testing of such hybrids showed excellent tree size control, good yields, and juice quality; however, there were usually one or more problems with each hybrid, such as inadequate seed production for standard propagation, or poor tree survival at one or more locations. We have subsequently produced additional somatic hybrids of complementary rootstocks that appear to have solved these problems, which also include parentage for coldhardiness. Although replicated field trials of these somatic hybrid rootstock candidates were destroyed by the state-run canker eradication program, we were able to obtain yield and juice quality data over three consecutive seasons from a small blight tolerance trial in St. Cloud in collaboration with Mr. Orie Lee. Features of five such tree-size controlling somatic hybrid rootstock candidates will be presented, including information on seed production, tree size, yield, and juice quality. For example, the somatic hybrid of ‘Changsha’ mandarin + 50-7 trifoliate orange consistently produces 2.25 boxes of ‘Valencia’ fruit per tree with high juice quality on trees of similar size to those budded to Flying Dragon. These new somatic hybrid rootstocks should have good potential in emerging advanced production systems for Florida.
Communications in Mathematical Physics Calabi – Yau Volumes and Reflexive Polytopes

We study various geometrical quantities for Calabi–Yau varieties realized as cones over Gorenstein Fano varieties, obtained as toric varieties from reflexive polytopes in various dimensions. Focus is made on reflexive polytopes up to dimension 4 and the minimized volumes of the Sasaki–Einstein base of the corresponding Calabi–Yau cone are calculated. By doing so, we conjecture new bounds for the Sasaki–Einstein volume with respect to various topological quantities of the corresponding toric varieties. We give interpretations about these volume bounds in the context of associated field theories via the AdS/CFT correspondence.
Entropy-Based Algorithms in the Analysis of Biomedical Signals

Abstract Biomedical signals are frequently noisy and incomplete. They produce complex and high-dimensional data sets. In these mentioned cases, the results of traditional methods of signal processing can be skewed by noise or interference present in the signal. Information entropy, as a measure of disorder or uncertainty in the data, was introduced by Shannon. To date, many different types of entropy methods have appeared with many different application areas. The purpose of this paper is to present a short overview of some methods of entropy analysis and to discuss their suitability for use in the analysis of biomedical signals.
Deep Cost-Sensitive and Order-Preserving Feature Learning for Cross-Population Age Estimation

Facial age estimation from a face image is an important yet very challenging task in computer vision, since humans with different races and/or genders, exhibit quite different patterns in their facial aging processes. To deal with the influence of race and gender, previous methods perform age estimation within each population separately. In practice, however, it is often very difficult to collect and label sufficient data for each population. Therefore, it would be helpful to exploit an existing large labeled dataset of one (source) population to improve the age estimation performance on another (target) population with only a small labeled dataset available. In this work, we propose a Deep Cross-Population (DCP) age estimation model to achieve this goal. In particular, our DCP model develops a two-stage training strategy. First, a novel cost-sensitive multitask loss function is designed to learn transferable aging features by training on the source population. Second, a novel order-preserving pair-wise loss function is designed to align the aging features of the two populations. By doing so, our DCP model can transfer the knowledge encoded in the source population to the target population. Extensive experiments on the two of the largest benchmark datasets show that our DCP model outperforms several strong baseline methods and many state-of-the-art methods.
Software Implementation using Hardware-Based Verification for Secure Content Delivery

This paper presents a novel method for secure message transmission – the Software Implementation using Hardware-Based Verification for Secure Content Delivery (SIHBVSCD) method. This method incorporates a two-tier security protocol which allows messages to be verified at both the user level (coming from a particular user) and hardware level (originating from a particular machine) providing protection from espionage and/or clandestine manipulation of information. SIHBVSCD securely sets up a one-time symmetric key used for transmission, offering advantages over both the high theft/loss likelihood of smartcards and the inability of hardware-based verification for machines that do not contain hardware capable of remote attestation.
Marital Status Distribution of the U.K. Military: Does It Differ From the General Population?

ABSTRACT The U.K. media suggest that U.K. military personnel have high divorce rates; to date, these claims are not substantiated. Marital status distribution of the general population and military were compared using data from the Office for National Statistics' marital projections and a military cohort study. Overall, military personnel were more likely to be married and less likely to be divorced than were the general population. Women in the military and married military personnel younger than 30 years of age are more likely to report divorce. Military welfare services might target these groups with programs assisting marital relationships.