Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment with suboptimal doses of raltegravir leads to aberrant HIV-1 integrations

Integration of the DNA copy of the HIV-1 genome into a host chromosome is required for viral replication and is thus an important target for antiviral therapy. The HIV-encoded enzyme integrase (IN) catalyzes two essential steps: 3′ processing of the viral DNA ends, followed by the strand transfer reaction, which inserts the viral DNA into host DNA. Raltegravir binds to IN and blocks the integration of the viral DNA. Using the Rous sarcoma virus-derived vector RCAS, we previously showed that mutations that cause one viral DNA end to be defective for IN-mediated integration led to abnormal integrations in which the provirus had one normal and one aberrant end, accompanied by rearrangements in the host genome. On the basis of these results, we expected that suboptimal concentrations of IN inhibitors, which could block one of the ends of viral integration, would lead to similar aberrant integrations. In contrast to the proviruses from untreated cells, which were all normal, ∼10–15% of the proviruses isolated after treatment with a suboptimal dose of raltegravir were aberrant. The aberrant integrations were similar to those seen in the RCAS experiments. Most of the aberrant proviruses had one normal end and one aberrant end and were accompanied by significant rearrangements in the host genome, including duplications, inversions, deletions and, occasionally, acquisition of sequences from other chromosomes. The rearrangements of the host DNA raise concerns that these aberrant integrations might have unintended consequences in HIV-1–infected patients who are not consistent in following a raltegravir-containing treatment regimen.
Scientific Article Recommendation by using Distributed Representations of Text and Graph

Scientific article recommendation problem deals with recommending similar scientific articles given a query article. It can be categorized as a content based similarity system. Recent advancements in representation learning methods have proven to be effective in modeling distributed representations in different modalities like images, languages, speech, networks etc. The distributed representations obtained using such techniques in turn can be used to calculate similarities. In this paper, we address the problem of scientific paper recommendation through a novel method which aims to combine multimodal distributed representations, which in this case are: 1. distributed representations of paper's content, and 2. distributed representation of the graph constructed from the bibliographic network. Through experiments we demonstrate that our method outperforms the state-of-the-art distributed representation methods in text and graph, by 29.6% and 20.4%, both in terms of precision and mean-average-precision respectively.
An electrostatic interaction between TEA and an introduced pore aromatic drives spring-in-the-door inactivation in Shaker potassium channels

Slow inactivation of Kv1 channels involves conformational changes near the selectivity filter. We examine such changes in Shaker channels lacking fast inactivation by considering the consequences of mutating two residues, T449 just external to the selectivity filter and V438 in the pore helix near the bottom of the selectivity filter. Single mutant T449F channels with the native V438 inactivate very slowly, and the canonical foot-in-the-door effect of extracellular tetraethylammonium (TEA) is not only absent, but the time course of slow inactivation is accelerated by TEA. The V438A mutation dramatically speeds inactivation in T449F channels, and TEA slows inactivation exactly as predicted by the foot-in-the-door model. We propose that TEA has this effect on V438A/T449F channels because the V438A mutation produces allosteric consequences within the selectivity filter and may reorient the aromatic ring at position 449. We investigated the possibility that the blocker promotes the collapse of the outer vestibule (spring-in-the-door) in single mutant T449F channels by an electrostatic attraction between a cationic TEA and the quadrupole moments of the four aromatic rings. To test this idea, we used in vivo nonsense suppression to serially fluorinate the introduced aromatic ring at the 449 position, a manipulation that withdraws electrons from the aromatic face with little effect on the shape, net charge, or hydrophobicity of the aromatic ring. Progressive fluorination causes monotonically enhanced rates of inactivation. In further agreement with our working hypothesis, increasing fluorination of the aromatic gradually transforms the TEA effect from spring-in-the-door to foot-in-the-door. We further substantiate our electrostatic hypothesis by quantum mechanical calculations.
The University of Michigan at DUC 2004

We present the results of Michigan’s participation in DUC 2004. Our system, MEAD, ranked as one of the top systems in four of the five tasks. We introduce our new feature, LexPageRank, a new measure of sentence centrality inspired by the prestige concept in social networks. LexPageRank gave promising results in multi-document summarization. Our approach for Task 5, biographical summarization, was simplistic, yet succesful. We used regular expression matching to boost up the scores of the sentences that are likely to contain biographical information patterns.
Personalized ranking of search results with implicitly learned user interest hierarchies

Web search engines are usually designed to serve all users, without considering the interests of individual users. Personalized web search incorporates an individual user's interests when deciding relevant results to return. We propose to learn a user profile, called a user interest hierarchy (UIH), from web pages that are of interest to the user. The user’s interest in web pages will be determined implicitly, without directly asking the user. Using the implicitly learned UIH, we study methods that (re)rank the results from a search engine. Experimental results indicate that our personalized ranking methods, when used with a popular search engine, can yield more relevant web pages for individual users.
Global Patterns of Diversity and Selection in Human Tyrosinase Gene

Global variation in skin pigmentation is one of the most striking examples of environmental adaptation in humans. More than two hundred loci have been identified as candidate genes in model organisms and a few tens of these have been found to be significantly associated with human skin pigmentation in genome-wide association studies. However, the evolutionary history of different pigmentation genes is rather complex: some loci have been subjected to strong positive selection, while others evolved under the relaxation of functional constraints in low UV environment. Here we report the results of a global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, to assess the role of its variation in the evolution of skin pigmentation differences among human populations. We observe a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints. A similar pattern was previously observed in the MC1R gene and concurs with UV radiation-driven model of skin color evolution by which mutations leading to lower melanin levels and decreased photoprotection are subject to purifying selection at low latitudes while being tolerated or even favored at higher latitudes because they facilitate UV-dependent vitamin D production. Our coalescent date estimates suggest that the non-synonymous variants, which are frequent in Europe and North Africa, are recent and have emerged after the separation of East and West Eurasian populations.
The role of dendritic inhibition in shaping the plasticity of excitatory synapses

Using computational tools we explored the impact of local synaptic inhibition on the plasticity of excitatory synapses in dendrites. The latter critically depends on the intracellular concentration of calcium, which in turn, depends on membrane potential and thus on inhibitory activity in particular dendritic compartments. We systematically characterized the dependence of excitatory synaptic plasticity on dendritic morphology, loci and strength, as well as on the spatial distribution of inhibitory synapses and on the level of excitatory activity. Plasticity of excitatory synapses may attain three states: “protected” (unchanged), potentiated (long-term potentiation; LTP), or depressed (long-term depression; LTD). The transition between these three plasticity states could be finely tuned by synaptic inhibition with high spatial resolution. Strategic placement of inhibition could give rise to the co-existence of all three states over short dendritic branches. We compared the plasticity effect of the innervation patterns typical of different inhibitory subclasses—Chandelier, Basket, Martinotti, and Double Bouquet—in a detailed model of a layer 5 pyramidal cell. Our study suggests that dendritic inhibition plays a key role in shaping and fine-tuning excitatory synaptic plasticity in dendrites.
Influence of Sintering Conditions on Electric Performance of Textured 92BNT-6BT-2KNN Ceramics

0.92(Bi0.5Na0.5)TiO3-0.06BaTiO3-0.02(K0.5Na0.5)NbO3(92BNT-6BT-2KNN) is a high-stain material due to the volume change which come from antiferroelectric-ferroelectric (AFE-FE) phase transformation. Textured 92BNT-6BT-2KNN with a Lotgering factor of 67% was obtained by templated grain growth (TGG) method using plate-like (Bi0.5Na0.5)TiO3（BNT）particles as templates. The influences of sintering process on Lotgering factor and strain were investigated. It was found that the Lotgering factor increased as sintering temperature increase and then decreased with further temperature increase. The changing tendency of polar and unipolar strain did not keep the same accordance with that of Lotgering factor. The maximum of Lotgering factor (79%) and polar strain (0.36%) was obtained when the sintering temperature was 1240°C and 1220°C, respectively, due to the decrease of density when high sintering temperature was employed. Also it was found that the lotgering factor and polar strain reached its highest values when the soaking time was 4h. All these proved that the density and grain orientation codetermined the strain of 92BNT-6BT-2KNN ceramics.
An energy-efficient level shifter for low-power applications

One effective way to reduce the power consumption of biomedical implantable devices is to employ different supply voltages for different parts of the system depending on the processing speed of each part. This, however, necessitates the use of voltage level converters. This paper presents a power-efficient voltage level-shifting architecture that is capable of converting low levels of input voltages (even sub-threshold levels) to high levels of output voltages. In order to reduce the transition time of the output signal and consequently power consumption, the proposed circuit utilizes a diode-connected transistor to reduce the swing of the critical node. Moreover, the pull-down network is also improved. Post-layout simulation results of the proposed structure in a 0.18-μm CMOS technology show that at the target design of input low supply voltage of 0.4 V and high supply voltage of 1.8 V, the level-shifter has a propagation delay of 31ns, a static power dissipation of 1.16nW, and a power dissipation of 0. 68μW for a 1-MHz input signal.
Daily dialysis in pregnancy

Pregnancy remains uncommon in dialysis patients. Current estimates of the frequency of conception are based on four surveys. The only complete survey comes from Belgium where all of the dialysis units in the country responded, and the rate of conception was reported as 0.3 per 100 patient-years A survey of American dialysis units reported pregnancy in 2.2% of dialysis patients over a 4-year period. The rate of conception in a Japanese survey was 3.4% of women of childbearing age, although the time period was not specified. A survey of dialysis units in Saudi Arabia reported pregnancies in 9% of married women on dialysis over a 5-year period. There is a widespread impression that the frequency of pregnancy in dialysis patients is increasing but the reliability of the estimates of the frequency of pregnancy in dialysis patients is questionable. A recent study from Holley and colleagues reports that 50% of women of childbearing age treated with dialysis have menstrual periods. This frequency represents an increase from previous reports in which all but 10% of women had no menses. Nephrologists have speculated, with little hard data, that changes in menstrual function can be attributed both to erythropoietin therapy and to better dialysis. It is not yet clear whether the widespread use of daily dialysis will result in a greater normalization of ovarian function or an increase in pregnancies. The outcome of pregnancies in womenwho conceive after starting dialysis remains poor. Only 59% of pregnancies that reach the second trimester result in surviving infants. Seventy-five percent of infants are born before 37 weeks of gestation and 25% are born before 28 weeks of gestation.
Neomycin is a potent secretagogue of mast cells that directly activates a GTP-binding protein involved in exocytosis

When loaded alongside GTP-gamma-S into ATP-permeabilized cells, neomycin, at concentrations below 1 mM, inhibits GTP-gamma-S-induced histamine secretion and phosphatidic acid formation (Cockcroft, S., and B. D. Gomperts, 1985. Nature (Lond.). 314: 534-536; Aridor, M. , L. M. Traub, and R. Sagi-Eisenberg. 1990. J. Cell Biol. 111:909-917). However, at higher concentrations internally applied neomycin induces histamine secretion in a process that is: (a) dose dependent; (b) dependent on the internal application of GTP; (c) independent of phosphoinositide breakdown; and (d) inhibited by pertussis toxin (PtX) treatment. These results indicate that neomycin can stimulate histamine secretion in a mechanism that bypasses phospholipase C (PLC) activation and yet involves a PtX-sensitive GTP-binding protein (G protein). Unlike its dual effects, when internally applied, neomycin induces histamine secretion from intact mast cells in a dose-dependent manner. Half-maximal and maximal effects are obtained at 0.5 and 1 mM neomycin, respectively. This process is rapid (approximately 30 s), is independent of external Ca2+, and is associated with phosphatidic acid formation, implying that neomycin can activate histamine secretion by a mechanism similar to that utilized by other basic secretagogues of mast cells. Neomycin stimulates fourfold the GTPase activity of cholate- solubilized rat brain membranes in a PtX-inhibitable manner. In addition neomycin, as well as the basic secretagogues of mast cells, compound 48/80, and mastoparan, significantly reduce (by approximately 80%) the ADP ribosylation of PtX substrates present in rat brain membranes. Taken together these data suggest that neomycin can stimulate secretion from mast cells by directly activating G proteins that play a role in stimulus-secretion coupling. When internally applied, neomycin presumably stimulates secretion by activating a G protein that is located downstream to PLC. This G protein serves as a substrate for PtX.
Porcine Splenic Hydrolysate has Antioxidant Activity in vivo and in vitro

The antioxidant capacity of porcine splenic hydrolysate (PSH) was studied in vitro and in vivo. Peptide hydrolysates were prepared, using the proteolytic enzyme Alcalase®. The molecular weights of PSH were 37,666, 10,673, 6,029, and 2,918 g/mol. Rats were fed a 5% (w/v) PSH diet, instead of a casein diet, for 4 wk. The food intake, body weight gain, and liver weight of rats in the PSH group were similar to those in the control (CONT) group. There were no differences in the serum total cholesterol, triglyceride, total protein, or albumin levels between PSH and CONT groups. However, the level of in vivo hepatic lipid peroxidation in PSH group was significantly lower than that in CONT. In vivo hepatic catalase and glutathione peroxidase activities in the PSH group were significantly higher than those in the control group. The in vitro protein digestibility of PSH was lower than that of casein. The in vitro trolox equivalent antioxidant capacity of PSH was significantly higher than that of the peptide hydrolysate from casein. The in vitro radical scavenging activities of PSH were significantly higher than those of the peptide hydrolysate from casein. The present findings suggest that porcine splenic peptides improve the antioxidant status in rats by enhancing hepatic catalase and GSH-Px activities, and indicate a potential mechanism of radical scavenging activity during gastrointestinal passage.
Texture Measurements of Hydroxyapatite Crystallites at Bone-Implant Interfaces in Sheep Tibia

The preferred orientation of hydroxyapatite Ca10(PO4)6(OH)2 (HAp) crystallites at the interface bone-implant in sheep tibia bones has been measured with the neutron 2-axis diffractometer D20 at the Institut Max von Laue-Paul Langevin, extracted 60 days after implantation. The implant has two faces, one coated and one non-coated with plasma-sprayed HAp (80 µm). We probed the samples with a spatial resolution of 0.5 mm started from the interface in order to inspect the reorganisation of the HAp crystallite distribution after implantation.
Automated target selection for DrivenShape

DrivenShape is a data-driven deformation that uses pre-computed data (a.k.a. targets) to approximate the effects of a computationally expensive cloth simulation [Kim and Vendrovsky 2008]. Rather than computing a true, accurate solution, DrivenShape produces a quick approximation that satisfies an acceptable margin of error, where error is defined as a difference in appearance or shape.
The Power of Asymmetry in Binary Hashing

When approximating binary similarity using the hamming distance between short binary hashes, we show that even if the similarity is symmetric, we can have shorter and more accurate hashes by using two distinct code maps. I.e. by approximating the similarity between x and x′ as the hamming distance between f (x) and g(x′), for two distinct binary codes f, g, rather than as the hamming distance between f (x) and f (x′).
A corroborative approach to verification and validation of human–robot teams

We present an approach for the verification and validation (V&V) of robot assistants in the context of human–robot interactions, to demonstrate their trustworthiness through corroborative evidence of their safety and functional correctness. Key challenges include the complex and unpredictable nature of the real world in which assistant and service robots operate, the limitations on available V&V techniques when used individually, and the consequent lack of confidence in the V&V results. Our approach, called corroborative V&V, addresses these challenges by combining several different V&V techniques; in this paper we use formal verification (model checking), simulation-based testing, and user validation in experiments with a real robot. This combination of approaches allows V&V of the human–robot interaction task at different levels of modeling detail and thoroughness of exploration, thus overcoming the individual limitations of each technique. We demonstrate our approach through a handover task, the most critical part of a complex cooperative manufacturing scenario, for which we propose safety and liveness requirements to verify and validate. Should the resulting V&V evidence present discrepancies, an iterative process between the different V&V techniques takes place until corroboration between the V&V techniques is gained from refining and improving the assets (i.e., system and requirement models) to represent the human–robot interaction task in a more truthful manner. Therefore, corroborative V&V affords a systematic approach to “meta-V&V,” in which different V&V techniques can be used to corroborate and check one another, increasing the level of certainty in the results of V&V.
A systems biology approach for elucidating the interaction of curcumin with Fanconi anemia FANC G protein and the key disease targets of leukemia

Abstract Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia. However, its complete mechanism is not elucidated. Herein, a systems biology approach for elucidating the therapeutic potential of curcumin against FA and leukemia is investigated by analyzing the computational molecular interactions of curcumin ligand with FANC G of FA and seven other key disease targets of leukemia. The proteins namely DOT1L, farnesyl transferase (FDPS), histone decetylase (EP3000), Polo-like kinase (PLK-2), aurora-like kinase (AUKRB), tyrosine kinase (ABL1), and retinoic acid receptor alpha (RARA) were chosen as disease targets for leukemia and modeled structure of FANC G protein as the disease target for FA. The docking investigations showed that curcumin had a very high binding affinity of −8.1 kcal/mol with FANC G protein. The key disease targets of leukemia namely tyrosine kinase (ABL1), aurora-like kinase (AUKRB), and polo-like kinase (PLK-2) showed that they had the comparable binding affinities of −9.7 k cal/mol, −8.7 k cal/mol, and −8.6 k cal/mol, respectively with curcumin. Further, the percentage similarity scores obtained from PAM50 using EMBOSS MATCHER was shown to provide a clue to understand the structural relationships to an extent and to predict the binding affinity. This investigation shows that curcumin effectively interacts with the disease targets of both FA and leukemia.
Quantitative Trait Loci Analysis of Primary Cell Wall Composition in Arabidopsis 1

Quantitative trait loci (QTL) analysis was used to identify genes underlying natural variation in primary cell wall composition in Arabidopsis ( Arabidopsis thaliana ). The cell walls of dark-grown seedlings of a Bay-0 3 Shahdara recombinant inbred line population were analyzed using three miniaturized global cell wall ﬁngerprinting techniques: monosaccharide composition analysis by gas chromatography, xyloglucan oligosaccharide mass proﬁling, and whole-wall Fourier-transform infrared microspectroscopy. Heritable variation and transgression were observed for the arabinose-rhamnose ratio, xyloglucan side- chain composition (including O- acetylation levels), and absorbance for a subset of Fourier-transform infrared wavenumbers. In total, 33 QTL, corresponding to at least 11 different loci controlling dark-grown hypocotyl length, pectin composition, and levels of xyloglucan fucosylation and O- acetylation, were identiﬁed. One major QTL, accounting for 51% of the variation in the arabinose-rhamnose ratio, affected the number of arabinan side chains presumably attached to the pectic polysaccharide rhamnogalacturonan I, paving the way to positional cloning of the ﬁrst gene underlying natural variation in pectin structure. Several QTL were found to be colocalized, which may have implications for the regulation of xyloglucan metabolism. These results demonstrate the feasibility of combining ﬁngerprinting techniques, natural variation, and quantitative genetics to gain original insight into the molecular mechanisms underlying the structure and metabolism of cell wall polysaccharides.