Miracle-dz/UniFAR-FTUs huggingface dataset:
Haploinsufficiency of MEIS2 is associated with orofacial clefting and learning disability

MEIS2 is a homeodomain‐containing transcription factor of the TALE superfamily that has been proven important for development. We confirm and extend a recent single clinical report stating that deletions in MEIS2 can cause cleft palate [Crowley et al. (2010); Am J Med Genet 152A:1326–1327]. Here we report on five additional patients with 15q14 deletions of sizes 0.6, 0.6, 1.0, 1.9, and 4.8 Mb, respectively, all involving MEIS2. In addition, we present a family with four affected individuals and an intragenic 58 kb direct duplication disrupting MEIS2. In total, 7/9 cases had clefting, from mild (submucous cleft palate) to severe (cleft lip and palate), and 3/9 cases had ventricular septal defects. All cases had delayed motor development and most had learning disability, at worst in the mild intellectual disability range. The cases had overlapping facial features (broad forehead, finely arched eyebrows, mildly shortened philtrum, and tented upper lip) but individually they were not considered to be dysmorphic. Our results show that MEIS2 is a gene needed for palate closure. In syndromic cases of cleft palate, MEIS2 should be considered among the candidate genes, for example, in cases without 22q11.2 deletions. © 2014 Wiley Periodicals, Inc.
American and American/Asian genotypes of dengue virus differ in mosquito infection efficiency: candidate molecular determinants of productive vector infection

Introduction. Genotype replacement has been associated with dramatic increases in epidemic dengue and severe dengue cases in Latin America, but little is known concerning the determinants of these genotypic sweeps. More efficient productive infection of Aedes aegypti mosquitoes could condition such sweeps. Viruses that more efficiently infect and are transmitted by mosquitoes will have a better chance of being transmitted to the next susceptible host and would thus have greater epidemic potential. Objectives. The objectives were to: determine differences in vector infection potential for DENV-2 isolates representing two DENV-2 genotypes from the Yucatan Peninsula of Mexico and to identify candidate viral molecular determinants of phenotypic differences. Materials and Methods. DENV-2 American and American/Asian isolates from the Yucatan Peninsula were characterized in vivo in mosquitoes. Midgut infection and virus dissemination to infect salivary glands for productive mosquito infection was determined by indirect inmunofluorescence assay and mosquitoes were titrated to determine viral load. The E gene and 3´ UTR were sequenced to investigate potential molecular correlates of efficient vector infection. Results. All viruses from both genotypes were equivalent in their ability to infect mosquito midguts. However, the viruses from the America/ Asian genotype efficiently disseminated to infect the salivary glands in Aedes aegypti mosquitoes but the American genotypes did not. Sequence analysis of the E protein gene and the 3’ UTR of the viruses suggested candidate molecular determinants of the vector infection phenotypes. Conclusions. DENV-2 virus genotypes differ in vector competence; American/Asian genotypes efficiently disseminate from the midgut to infect salivary glands to be transmitted. Some of the amino acid changes in E protein and nucleotides in the 3´UTR may be related to this phenotype.
Chiral amplification of chiral porphyrin derivatives by templated heteroaggregation.

The solvent-promoted aggregation of amphiphilic porphyrin derivatives 1H2 and 2H2, possessing a chiral cationic or anionic functionality, respectively, occurs with the formation of chiral supramolecular structures. If the aggregation of 1H2 (P*(+) in the artwork) is carried out in the presence of preformed aggregates of 2H2 (P*(−) in the artwork), a remarkable amplification of the supramolecular chirality is observed (P*(+) + P*(−), in the picture) as a consequence of an electrostatic templation effect. The templated heteroaggregates resulted also in increased stability toward the presence of an achiral, negatively charged, porphyrin derivative.
Safety, security, and object-oriented programming

When safety-critical software malfunctions people lives are in danger. When security-critical software is cracked national security or economic activity may be at risk.As more and more software embraces object-oriented programming (OOP) safety-critical and security-critical projects feel compelled to use object-orientation. But what are the guarantees of OOP in terms of safety and security? Are the design goals of OOP aligned with those of safe and secure software (S3) systems? In the following sections we look at key OOP aspects and analyze some of the hazards they introduce with respect to S3 and outline a possible way of addressing these vulnerabilities. Specifically, after a quick overview of OOP in section 2, section 3 deals with inheritance and shows some of its hazards in terms of S3 along with possible remedies. Section 4 focuses on dynamic binding and suggests a safer and more secure implementation than what is conventionally done. Finally, section 5 looks at testing programs with dynamic binding.
Stair negotiation made easier using novel interactive energy-recycling assistive stairs

Here we show that novel, energy-recycling stairs reduce the amount of work required for humans to both ascend and descend stairs. Our low-power, interactive, and modular steps can be placed on existing staircases, storing energy during stair descent and returning that energy to the user during stair ascent. Energy is recycled through event-triggered latching and unlatching of passive springs without the use of powered actuators. When ascending the energy-recycling stairs, naive users generated 17.4 ± 6.9% less positive work with their leading legs compared to conventional stairs, with the knee joint positive work reduced by 37.7 ± 10.5%. Users also generated 21.9 ± 17.8% less negative work with their trailing legs during stair descent, with ankle joint negative work reduced by 26.0 ± 15.9%. Our low-power energy-recycling stairs have the potential to assist people with mobility impairments during stair negotiation on existing staircases.
Record low loss, record high FOM optical fiber with manufacturable process

Record-low loss of 0.149dB/km at 1550nm is realized by pure-silica-core fiber having optimally enlarged Aeff, which indicates record-high figure-of-merit for digital coherent system. Mass-productivity is verified with 7,000km long fabrication whose averaged loss of 0.154dB/km.
The making of chalcolithic assembly places: Trypillia megasites as materialized consensus among equal strangers?

ABSTRACT In the last decade, we have witnessed a second methodological revolution in research into the Trypillia megasites of Ukraine – the largest sites in fourth-millennium BC Europe and possibly the world. However, these methodological advances have not been accompanied by parallel advances in the understanding of the nature and development of the megasites. New data have led to a ‘tipping point’ which leads us to reject the traditional interpretation of megasites as long-term centres permanently occupied by tens of thousands of people. The contention of the alternative approach is the temporary, short-term dwelling of much smaller populations at megasites such as Nebelivka. In this article, the authors present two alternative models for the gradual emergence of the highly structured plan of the Trypillia megasite.
A maximum entropy Markov model for chunking

This paper presents a new chunking method based on maximum entropy Markov models (MEMM). MEMM is described in detail that combines transition probabilities and conditional probabilities of states effectively. The conditional probabilities of states are estimated by maximum entropy (ME) theory. The transition probabilities of the states are estimated by N-gram model in which interpolation smoothing algorithm is utilized on the basis of analyzing chunking spec. Experiment results show that this approach achieves an impressive performance: 92.53% in F-score on the open data sets of CoNLL-2000 shared task. The performance of the algorithm is close to the state-of-the-art.
Challenges and issues in veterinary pharmacology and animal health 2004—Preface

Since publishing the first AAPS PharmSci veterinary theme issue in 2002, the Food and Drug Administration Center for Veterinary Medicine (CVM) has enjoyed numerous accomplishments. Between the year 2002 and July 2005, CVM published 43 guidance documents (Table 1). Sixteen of these guidance documents were written in collaboration with the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH), a trilateral (EAU-Japan-USA) program aimed at harmonizing technical requirements for veterinary product registration.1
Aflatoxin B1 - Prevention of Its Genetic Damage by Means of Chemical Agents

Mycotoxins are structurally diverse groups largely composed of small molecular weight chemicals, which are generally produced by the mycelial structure of filamentous fungi. These toxins are secondary metabolites mainly synthesized during the end of the mould exponential phase of growth. They appear to have no biological significance with respect to their growth/development or competitiveness, but when ingested by higher vertebrates and other animals they can cause diseases called mycotoxicoses (Kabak et al., 2006; MadrigalSantillan et al., 2010). Aflatoxin B1 (AFB1), in particular, is a tetrahydrofuran moiety fused to a coumarin ring and was chemically classified as cyclopenta[c]furo[3',2':4,5]furo[2,3h][1] benzopyran-1,11-dione,2,3,6a,9a-tetrahydro-4-methoxy-, (6aR,9aS) (Eaton et al., 1994; Hedayati et al., 2007) (Figure 1).
Changes in posterior scleral collagen microstructure in canine eyes with an ADAMTS10 mutation

Purpose We aimed to characterize alterations in the posterior scleral collagen microstructure before detectable disease onset in a canine model of open-angle glaucoma caused by an ADAMTS10 mutation. Methods Collagen orientation, anisotropy degree (proportion of preferentially aligned collagen), and relative density were measured at 0.4 mm spatial resolution using synchrotron wide-angle X-ray scattering. For statistical evaluation of structure parameters, regional averages of the peripapillary and mid-posterior sclera were compared between ADAMTS10 mutant (affected) dogs (n = 3) and age-matched (carrier) controls (n = 3). Results No marked differences in the general pattern of preferential collagen fibril orientation were noted between the control and affected dogs. The peripapillary sclera of all specimens featured strongly aligned circumferential collagen ringing the optic nerve head. Collagen anisotropy was significantly reduced in the mid-posterior sclera of the affected dogs (carrier: 0.27±0.11; affected: 0.24±0.10; p = 0.032) but was not statistically significantly different in the peripapillary sclera (carrier: 0.46±0.15; affected: 0.45±0.17; p = 0.68). Collagen density was statistically significantly reduced in the affected dogs for the mid-posterior sclera (carrier: 28.1±9.14; affected: 18.3±5.12; p<0.0001) and the peripapillary sclera (carrier: 34.6±9.34; affected: 21.1±6.97; p = 0.0002). Conclusions Significant alterations in the posterior scleral collagen microstructure are present before the onset of clinical glaucoma in ADAMTS10 mutant dogs. A reduction in fibrous collagen density is likely an important contributory factor in the previously reported mechanical weakening of the sclera in this model. Baseline scleral abnormalities have the potential to interact with intraocular pressure (IOP) elevations in determining the course of glaucoma progression in animal models of the disease, and potentially in human glaucoma.
Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum‐based chemotherapy in advanced nonsmall‐cell lung cancer patients

Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum‐based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1‐141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall‐cell lung cancer (NSCLC) patients after treatment with platinum‐based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p = 0.005], while XRCC1 399 GA, or GA+AA, was associated with poor OS in short‐term period (HR 1.718, p = 0.003; HR 1.691, p = 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short‐term period (HR 1.929, p < 0.001). Furthermore, patients with XRCC1 399 variant allele (GA+AA) had higher risk of hematologic toxicity (p = 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1‐141 GG variant, had reduced risk of gastrointestinal toxicity (p = 0.015 and p = 0.023, respectively). The data from the current study provide evidence that OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1‐141T/G polymorphisms may be useful in predicting clinical outcomes in patients with advanced inoperable NSCLC that will undergo platinum‐based chemotherapy.
Visual sphere and Thurston's boundary of the Universal Teichm\"uller space

Thurston's boundary to the universal Teichm\"uller space $T(\mathbb{D})$ is the space $PML_{bdd}(\mathbb{D})$ of projective bounded measured laminations of $\mathbb{D}$. A geodesic ray in $T(\mathbb{D})$ is of Teichm\"uller type if it shrinks vertical foliation of an integrable holomorphic quadratic differential. In a prior work we established that each Teichm\"uller geodesic ray limits to a multiple (by the reciprocal of the length of the leaves) of vertical foliation of the quadratic differential. Certain non-integrable holomorphic quadratic differential induce geodesic rays and we consider their limit points in $PML_{bdd}(\mathbb{D})$. Somewhat surprisingly, the support of the limiting projective measured laminations might be a geodesic lamination whose leaves are not homotopic to leaves of either vertical or horizontal foliation of the non-integrable holomorphic quadratic differential.
High-Performance Prediction of Agonists on Human Estrogen Receptor Based on Chemical Structures

Many agonists for the estrogen receptor are known to disrupt endocrine functioning. We have developed a computational model that predicts agonists for the estrogen receptor ligandbinding domain in an assay system. Our model was entered into the Tox21 Data Challenge 2014, a computational toxicology competition organized by the National Center for Advancing Translational Sciences. This competition aims to find high-performance predictive models for various adverse-outcome pathways, including the estrogen receptor. Our predictive model, which is based on the random forest method, delivered the best performance in its competition category. In the current study, the predictive performance of the random forest models was improved by strictly adjusting the hyperparameters to avoid overfitting. The random forest models were optimized from 4,000 descriptors simultaneously applied to 10,000 activity assay results for the estrogen receptor ligand-binding domain, which have been measured and compiled by Tox21. At this time, our model delivers the highest predictive power on estrogen receptor agonists in the world. Furthermore, analysis of the optimized model revealed some important features of the agonists, such as the number of hydroxyl groups in the molecules.
Breeder age affects small intestine development of broiler chicks with immediate or delayed access to feed

1. The relationship between breeder age and chick gastrointestinal tract development to 21 days of age, as influenced by immediate or delayed access to feed, was examined in three consecutive trials. 2. Ross 708 chicks, derived from breeder flocks at 31 (young), 40 (middle) and 63 (old) weeks of age were placed randomly into either a control group with immediate access to feed and water, or a 48 h feed delayed (FD) group with free access to water. 3. FD negatively affected body weight (BW) of chicks derived from young and old flocks through the first and second weeks of age, respectively. Chicks from the older flock absorbed more yolk in the first 48 h with no FD effect. When feed was made available, chicks from the FD group showed a large increase in small intestine weight relative to BW, surpassing (P < 0·05) the control groups across all breeder flock ages. 4. Morphological measurements in all intestinal sections had higher values in chicks derived from the middle age breeder flock. FD to newly hatched chicks from the young breeder flock shortened villi (P < 0·01), decreased crypt depth and villus surface area (P < 0·001) in the duodenum through the first week post hatch. 5. Crypt depths were maximised between 7 and 14 d post-hatch in chicks from young and old breeder flocks, but crypt depths in chicks from the middle aged flocks continued to deepen. 6. The increased crypt depth may augment the number of enterocytes available for villus growth, and facilitate longer villi and greater villus surface area, in chicks from the middle age flocks. Intestinal morphological variation was associated with breeder flock age, which accounted for differential growth in chicks derived from young, middle, and old aged breeder flocks.
Regional Entrepreneurial Opportunities in the Biotech Industry: Exploring the Transition from Award-Winning Nascent Entrepreneurs to Real Start-Ups

Knowledge of factors that determine the transition from nascent entrepreneurship to real entrepreneurship is of major importance for policies aiming to stimulate start-ups effectively. Scholars have concentrated mainly on person-specific factors to explain transition probabilities, and environmental characteristics have been relatively neglected. Given that entrepreneurship is a strongly localized phenomenon, this paper argues that regional entrepreneurial opportunities are a driving force behind the transition from nascent entrepreneurship to new venture creation. Based on unique data from 103 nascent entrepreneurs in the German biotechnology industry, we empirically assess the importance of regional entrepreneurial opportunities for transition probabilities. Further, we introduce a new approach to measure nascent entrepreneurship by capturing details of individuals who participate actively in start-up competitions and have won at least one of these. Controlling for technology and individual characteristics, we find strong support for our hypotheses relating to the significant impact of general regional opportunities, specific regional opportunities and the entrepreneurial environment on the probability of transition from award-winning nascent entrepreneurs to real start-ups.
Phylogenetic signal in growth and reproductive traits and in their plasticity: the Descurainia radiation in the Canary Islands

Despite the extensive use of phylogenetic methods in comparative plant biology, there is little information on how traits and their plastic responses can be affected by phylogenetic constraints (i.e. limitations in phenotypic expression resulting from the phylogenetic history of a lineage), particularly in plant radiations that may have occurred over a relatively short time period. In this study, we examined phylogenetic constraints in a monophyletic group of species of Descurainia (Brassicaceae) endemic to the Canary Islands. We measured growth and reproductive traits in a glasshouse experiment representing 17 populations of eight taxa previously analysed in a phylogenetic context. Two water availability treatments were used to assess the plasticity of the examined traits. Most of the traits did not show strong phylogenetic signal; only weak evidence for phylogenetic constraint was found in traits related to reproduction (total number of flowers, onset of flowering) and biomass allocation to roots. Substantial levels of plasticity were observed in all the examined traits, but plasticity showed little interaction between treatment and taxon, suggesting little divergence among taxa. Our study provides evidence that phylogenetic constraints in these quantitative traits, including their plastic expression, have not played a significant role in the pattern of phenotypic diversification of this island plant group. Phenotypic plasticity may thus have favoured adjustment to the habitats occupied by each species during the radiation process. © 2014 The Linnean Society of London, Botanical Journal of the Linnean Society, 2014, 174, 384–398.
On the number of summands in Zeckendorf decompositions

Zeckendorf proved that every positive integer has a unique representation as a sum of non-consecutive Fibonacci numbers. Once this has been shown, it's natural to ask how many summands are needed. Using a continued fraction approach, Lekkerkerker proved that the average number of such summands needed for integers in $[F_n, F_{n+1})$ is $n / (\varphi^2 + 1) + O(1)$, where $\varphi = \frac{1+\sqrt{5}}2$ is the golden mean. Surprisingly, no one appears to have investigated the distribution of the number of summands; our main result is that this converges to a Gaussian as $n\to\infty$. Moreover, such a result holds not just for the Fibonacci numbers but many other problems, such as linear recurrence relation with non-negative integer coefficients (which is a generalization of base $B$ expansions of numbers) and far-difference representations. In general the proofs involve adopting a combinatorial viewpoint and analyzing the resulting generating functions through partial fraction expansions and differentiating identities. The resulting arguments become quite technical; the purpose of this paper is to concentrate on the special and most interesting case of the Fibonacci numbers, where the obstructions vanish and the proofs follow from some combinatorics and Stirling's formula; see [MW] for proofs in the general case.
Medical Homes for Children with Special Health Care Needs: A Program Evaluation

Purpose. The purpose of the current study is to evaluate the effectiveness of a pilot project providing a medical home to children with special health care needs (CSHCN). This study differs from previous work in that it monitors a cohort of CSHCN one year prior to and two years after participation in a medical home intervention utilizing a quasi-experimental design. Results. The groups being compared demonstrated descriptive differences in emergency room (ER) and preventive visits. Statistically significant differences in ER visits were achieved by the second intervention year. Conclusions. The current research demonstrates that a medical home can have demonstrable effect on utilization of preventive and emergency care by CSHCN. Limitations of the current research include small sample size and lack of information on acuity and quality of life.